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Study flow diagram
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Figure 1

Study flow diagram

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study
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Figure 2

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies
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Figure 3

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies

Network plot for all the outcomes at class‐level The size of the nodes is proportional to the total number of participants allocated to each intervention and the thickness of the lines proportional to the number of studies evaluating each direct comparison.AE: adverse events; PASI: Psoriasis Area and Severity Index; PGA: Physician Global Assessment; QoL: quality of life; SAE: serious adverse events
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Figure 4

Network plot for all the outcomes at class‐level

The size of the nodes is proportional to the total number of participants allocated to each intervention and the thickness of the lines proportional to the number of studies evaluating each direct comparison.

AE: adverse events; PASI: Psoriasis Area and Severity Index; PGA: Physician Global Assessment; QoL: quality of life; SAE: serious adverse events

Network plot for all the outcomes at drug‐level The size of the nodes is proportional to the total number of participants allocated to each intervention and the thickness of the lines proportional to the number of studies evaluating each direct comparison.ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumabAE: adverse events; PASI: Psoriasis Area and Severity Index; PGA: Physician Global Assessment; QoL: quality of life; SAE: serious adverse events
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Figure 5

Network plot for all the outcomes at drug‐level

The size of the nodes is proportional to the total number of participants allocated to each intervention and the thickness of the lines proportional to the number of studies evaluating each direct comparison.

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

AE: adverse events; PASI: Psoriasis Area and Severity Index; PGA: Physician Global Assessment; QoL: quality of life; SAE: serious adverse events

Relative effects of the class‐level intervention as estimated from the network meta‐analysis model Drugs are reported in order of primary benefit ranking. Each cell contains the risk ratio (RR) (for dichotomous outcomes: PASI 90, serious adverse events, PASI 75, PGA 0/1, adverse events) or the standardised mean difference (SMD) (for the quality‐of‐life outcome), plus the 95% confidence interval, of the class level in the respective column versus the class level in the respective row. RRs larger than 1 for the lower triangle and smaller than 1 (or SMDs smaller than zero) for the upper triangle favour the treatment on the left. Significant results are bolded and underscored.AE: adverse events; PASI: Psoriasis Area and Severity Index; PGA: Physician's Global Assessment; QoL: quality of life; SAE: serious adverse events
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Figure 6

Relative effects of the class‐level intervention as estimated from the network meta‐analysis model

Drugs are reported in order of primary benefit ranking. Each cell contains the risk ratio (RR) (for dichotomous outcomes: PASI 90, serious adverse events, PASI 75, PGA 0/1, adverse events) or the standardised mean difference (SMD) (for the quality‐of‐life outcome), plus the 95% confidence interval, of the class level in the respective column versus the class level in the respective row. RRs larger than 1 for the lower triangle and smaller than 1 (or SMDs smaller than zero) for the upper triangle favour the treatment on the left. Significant results are bolded and underscored.

AE: adverse events; PASI: Psoriasis Area and Severity Index; PGA: Physician's Global Assessment; QoL: quality of life; SAE: serious adverse events

Relative effects of the intervention as estimated from the network meta‐analysis model for Psoriasis Area and Severity Index (PASI) 90 and serious adverse events (SAEs) Drugs are reported in order of primary benefit ranking. Each cell contains the risk ratio (RR) and 95% confidence interval for the two primary outcomes (PASI 90 and SAEs) of the intervention in the respective column versus the class level in the respective row. RRs larger than 1 for the lower triangle and smaller than 1 for the upper triangle favour the treatment on the left. Significant results are highlighted in grey.ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; τ (Tau): estimated heterogeneity standard deviation parameter; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab
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Figure 7

Relative effects of the intervention as estimated from the network meta‐analysis model for Psoriasis Area and Severity Index (PASI) 90 and serious adverse events (SAEs)

Drugs are reported in order of primary benefit ranking. Each cell contains the risk ratio (RR) and 95% confidence interval for the two primary outcomes (PASI 90 and SAEs) of the intervention in the respective column versus the class level in the respective row. RRs larger than 1 for the lower triangle and smaller than 1 for the upper triangle favour the treatment on the left. Significant results are highlighted in grey.

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; τ (Tau): estimated heterogeneity standard deviation parameter; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

Relative effects of the intervention as estimated from the network meta‐analysis model for Psoriasis Area and Severity Index (PASI 75) and adverse events (AEs) Drugs are reported in order of primary benefit ranking. Each cell contains the Risk Ratio (RR) and 95% confidence interval for the two secondary outcomes (PASI 75 and adverse events) of the intervention in the respective column versus the comparator in the respective row. RRs larger than 1 for the lower triangle and smaller than 1 for the upper triangle favour the treatment on the left. Significant results are are highlighted in grey.ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; τ (Tau): estimated heterogeneity standard deviation parameter; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab
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Figure 8

Relative effects of the intervention as estimated from the network meta‐analysis model for Psoriasis Area and Severity Index (PASI 75) and adverse events (AEs)

Drugs are reported in order of primary benefit ranking. Each cell contains the Risk Ratio (RR) and 95% confidence interval for the two secondary outcomes (PASI 75 and adverse events) of the intervention in the respective column versus the comparator in the respective row. RRs larger than 1 for the lower triangle and smaller than 1 for the upper triangle favour the treatment on the left. Significant results are are highlighted in grey.

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; τ (Tau): estimated heterogeneity standard deviation parameter; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

Relative effects of the intervention as estimated from the network meta‐analysis model for Physician's Global Assessment (PGA 0/1) and quality of life (QoL) Drugs are reported in order of primary benefit ranking. Each cell contains the risk ratio (RR) and 95% confidence interval (PGA 0/1) or standardized mean difference (quality of life) of the intervention in the respective column versus the comparator in the respective row. RRs larger than 1 for the lower triangle and smaller than 1 (or SMDs smaller than zero) for the upper triangle favour the treatment on the left. Significant results are are highlighted in grey.ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; τ (Tau): estimated heterogeneity standard deviation parameter; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab
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Figure 9

Relative effects of the intervention as estimated from the network meta‐analysis model for Physician's Global Assessment (PGA 0/1) and quality of life (QoL)

Drugs are reported in order of primary benefit ranking. Each cell contains the risk ratio (RR) and 95% confidence interval (PGA 0/1) or standardized mean difference (quality of life) of the intervention in the respective column versus the comparator in the respective row. RRs larger than 1 for the lower triangle and smaller than 1 (or SMDs smaller than zero) for the upper triangle favour the treatment on the left. Significant results are are highlighted in grey.

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; τ (Tau): estimated heterogeneity standard deviation parameter; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

Interval plot. Network meta‐analysis estimates of class‐level versus placebo for all the outcomes AE: adverse events; CI: confidence interval; PGA: Physician Global Assessment; PrI: predictive interval; QoL: Specific quality of life scale; RR: risk ratio; SAE: serious adverse events; SMD: standardised mean difference
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Figure 10

Interval plot. Network meta‐analysis estimates of class‐level versus placebo for all the outcomes

AE: adverse events; CI: confidence interval; PGA: Physician Global Assessment; PrI: predictive interval; QoL: Specific quality of life scale; RR: risk ratio; SAE: serious adverse events; SMD: standardised mean difference

Interval plot. Network meta‐analysis estimates of the interventions versus placebo for all the outcomes AE: adverse events; CI: confidence interval; PGA: Physician Global Assessment; PrI: predictive interval; QoL: Specific quality of life scale; RR: risk ratio; SAE: serious adverse events; SMD: standardised mean differenceACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab
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Figure 11

Interval plot. Network meta‐analysis estimates of the interventions versus placebo for all the outcomes

AE: adverse events; CI: confidence interval; PGA: Physician Global Assessment; PrI: predictive interval; QoL: Specific quality of life scale; RR: risk ratio; SAE: serious adverse events; SMD: standardised mean difference

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

Ranking plot. Ranking plot representing simultaneously the efficacy (x axis, PASI 90) and the acceptability (y axis, serious adverse events) of all the interventions (class and drug levels) for patients with moderate‐to‐severe psoriasis. Optimal treatment should be characterised by both high efficacy and acceptability and should be in the right upper corner of this graph.The different colours represent different groups of interventions considering their performance on both outcomes simultaneously. Interventions belonging to the same group are assumed having a similar performance when the two primary outcomes are considered jointlyACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumabPASI: Psoriasis Area and Severity Index; SAE: serious adverse events; SUCRA: surface under the cumulative ranking curve
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Figure 12

Ranking plot. Ranking plot representing simultaneously the efficacy (x axis, PASI 90) and the acceptability (y axis, serious adverse events) of all the interventions (class and drug levels) for patients with moderate‐to‐severe psoriasis. Optimal treatment should be characterised by both high efficacy and acceptability and should be in the right upper corner of this graph.

The different colours represent different groups of interventions considering their performance on both outcomes simultaneously. Interventions belonging to the same group are assumed having a similar performance when the two primary outcomes are considered jointly

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

PASI: Psoriasis Area and Severity Index; SAE: serious adverse events; SUCRA: surface under the cumulative ranking curve

Ranking for all the outcomes at class level AE: adverse events; PASI: Psoriasis Area and Severity Index; PGA: Physician Global Assessment; QoL: quality of life; SAE: serious adverse events
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Figure 13

Ranking for all the outcomes at class level

AE: adverse events; PASI: Psoriasis Area and Severity Index; PGA: Physician Global Assessment; QoL: quality of life; SAE: serious adverse events

Ranking for all the outcomes at drug level ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumabAE: adverse events; PASI: Psoriasis Area and Severity Index; PGA: Physician Global Assessment; QoL: quality of life; SAE: serious adverse events
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Figure 14

Ranking for all the outcomes at drug level

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

AE: adverse events; PASI: Psoriasis Area and Severity Index; PGA: Physician Global Assessment; QoL: quality of life; SAE: serious adverse events

PASI 90: direct summary effects for comparisons including at least two studies at class level AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small moleculesCI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio
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Figure 15

PASI 90: direct summary effects for comparisons including at least two studies at class level

AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small molecules

CI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio

Serious adverse effects: direct summary effects for comparisons including at least two studies at class level AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small moleculesCI: confidence interval; RR: risk ratio; SAE: serious adverse events
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Figure 16

Serious adverse effects: direct summary effects for comparisons including at least two studies at class level

AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small molecules

CI: confidence interval; RR: risk ratio; SAE: serious adverse events

Specific quality of life scale: direct summary effects for comparisons including at least two studies at class level AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small moleculesCI: confidence interval; QoL: specific quality of life scale; SMD: standardised mean difference
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Figure 17

Specific quality of life scale: direct summary effects for comparisons including at least two studies at class level

AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small molecules

CI: confidence interval; QoL: specific quality of life scale; SMD: standardised mean difference

Physician Global Assessment 0/1: direct summary effects for comparisons including at least two studies at class‐level AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small moleculesAE: adverse events; CI: confidence interval; PGA: Physician Global Assessment; RR: risk ratio
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Figure 18

Physician Global Assessment 0/1: direct summary effects for comparisons including at least two studies at class‐level

AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small molecules

AE: adverse events; CI: confidence interval; PGA: Physician Global Assessment; RR: risk ratio

PASI 75: direct summary effects for comparisons including at least two studies at class level AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small moleculesCI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio
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Figure 19

PASI 75: direct summary effects for comparisons including at least two studies at class level

AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small molecules

CI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio

Adverse effects : direct summary effects for comparisons including at least two studies at class‐level AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small moleculesAE: adverse events; CI: confidence interval; RR: risk ratio
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Figure 20

Adverse effects : direct summary effects for comparisons including at least two studies at class‐level

AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small molecules

AE: adverse events; CI: confidence interval; RR: risk ratio

Distributions of age and sex ratio of participants across comparisons ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab
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Figure 21

Distributions of age and sex ratio of participants across comparisons

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

Distributions of weight of participants and PASI score at baseline across comparisons ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab
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Figure 22

Distributions of weight of participants and PASI score at baseline across comparisons

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

Side‐splitting approach and design‐by‐treatment interaction model for inconsistency for Psoriasis Area and Severity Index (PASI) 90 Treatment codes: A = PBO, B = FUM, C = MTX, D = ACI, E = ALEFACEPT, F = CICLO, G = IFX, H = ADA, I = ETA, J = USK, K = SECU, L = IXE, M = BRODA, N = CERTO, O = APRE, P = TOFA, Q = GUSEL, R = TILDRA, S = PONE, T = ITOACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab
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Figure 23

Side‐splitting approach and design‐by‐treatment interaction model for inconsistency for Psoriasis Area and Severity Index (PASI) 90

Treatment codes: A = PBO, B = FUM, C = MTX, D = ACI, E = ALEFACEPT, F = CICLO, G = IFX, H = ADA, I = ETA, J = USK, K = SECU, L = IXE, M = BRODA, N = CERTO, O = APRE, P = TOFA, Q = GUSEL, R = TILDRA, S = PONE, T = ITO

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

Side‐splitting approach and design‐by‐treatment interaction model for inconsistency for serious adverse events (SAEs) Treatment codes: A = PBO, B = FUM, C = MTX, D = ACI, E = ALEFACEPT, F = CICLO, G = IFX, H = ADA, I = ETA, J = USK, K = SECU, L = IXE, M = BRODA, N = CERTO, O = APRE, P = TOFA, Q = GUSEL, R = TILDRA, S = PONE, T = ITOACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab
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Figure 24

Side‐splitting approach and design‐by‐treatment interaction model for inconsistency for serious adverse events (SAEs)

Treatment codes: A = PBO, B = FUM, C = MTX, D = ACI, E = ALEFACEPT, F = CICLO, G = IFX, H = ADA, I = ETA, J = USK, K = SECU, L = IXE, M = BRODA, N = CERTO, O = APRE, P = TOFA, Q = GUSEL, R = TILDRA, S = PONE, T = ITO

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

Inconsistency plots for all the outcomes at class‐level Inconsistency factor (IF) is calculated as the risk ratio (RR)/standardised mean difference (SMD) for direct evidence over the RR/SMD for indirect evidence in the loop with its 95% confidence interval (CI). IF value close to 0 indicates the absence of evidence for disagreement between direct and indirect evidence.AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small molecules
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Figure 25

Inconsistency plots for all the outcomes at class‐level

Inconsistency factor (IF) is calculated as the risk ratio (RR)/standardised mean difference (SMD) for direct evidence over the RR/SMD for indirect evidence in the loop with its 95% confidence interval (CI). IF value close to 0 indicates the absence of evidence for disagreement between direct and indirect evidence.

AIL12/23: anti‐IL12/23; AIL17: anti‐IL17; AIL23: anti‐IL23, ATA: anti‐TNF alpha; CSA: conventional systemic agents; OB: other biologics; PBO: placebo; SM: small molecules

Inconsistency plots for all the outcomes at drug level Inconsistency factor (IF) is calculated as the risk ratio (RR)/standardised mean difference (SMD) for direct evidence over the RR/SMD for indirect evidence in the loop with its 95% confidence interval (CI). IF value close to 0 indicates the absence of evidence for disagreement between direct and indirect evidence.ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab
Figuras y tablas -
Figure 26

Inconsistency plots for all the outcomes at drug level

Inconsistency factor (IF) is calculated as the risk ratio (RR)/standardised mean difference (SMD) for direct evidence over the RR/SMD for indirect evidence in the loop with its 95% confidence interval (CI). IF value close to 0 indicates the absence of evidence for disagreement between direct and indirect evidence.

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

Sensitivity analyses ‐ Interval plot. Network meta‐analysis results for primary outcomes (PASI 90 and serious adverse events) for trials with at least 50 participants. ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumabCI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio; SAE: serious adverse events
Figuras y tablas -
Figure 27

Sensitivity analyses ‐ Interval plot. Network meta‐analysis results for primary outcomes (PASI 90 and serious adverse events) for trials with at least 50 participants.

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

CI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio; SAE: serious adverse events

Sensitivity analyses ‐ Interval plot. Network meta‐analysis results for primary outcomes (PASI 90 and serious adverse events) for the completers. ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumabCI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio; SAE: serious adverse events
Figuras y tablas -
Figure 28

Sensitivity analyses ‐ Interval plot. Network meta‐analysis results for primary outcomes (PASI 90 and serious adverse events) for the completers.

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

CI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio; SAE: serious adverse events

Sensitivity analyses ‐ Interval plot. Network meta‐analysis results for primary outcomes (PASI 90 and serious adverse events) for all the interventions depending on the doses MTX ≥ 15/MTX other: methotrexate ≥ 15 mg per week/methotrexate < 15 mg per week; ALEFACEPT: alefacept all dosages; CICLO High: ciclosporin ≥ 3 mg/kg/day; ACI ≥ 35: acitretin ≥ 35 mg per day; FUM: fumaric acid esters all dosages; APRE 30: apremilast 30 mg twice daily; PONE 40: ponesimod 40 mg per day; TOFA 20: tofacitinib 20 mg per day; ETA 25/ETA 50: etanercept 25 mg twice a week/etanercept 50 mg twice a week; IFX: infliximab 5 mg/kg week O, 2, 4 every 6 weeks; ADA: adalimumab 80 mg Week 0, 40 mg Week 1 then 40 mg every other week; CERTO 200/400: certolizumab all dosages; USK 45: ustekinumab 45 mg; SECU 300/SECU other: secukinumab 300 mg every injection/secukinumab other dosages; IXE 200/IXE other: ixekizumab 200 mg per injection/ixekizumab other dosages; TILDRA 100/200: tildrakizumab all dosages; GUSEL 100: guselkumab 100 mg per injection; BRODA 210: brodalumab 210 mg per injectionCI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio; SAE: serious adverse events
Figuras y tablas -
Figure 29

Sensitivity analyses ‐ Interval plot. Network meta‐analysis results for primary outcomes (PASI 90 and serious adverse events) for all the interventions depending on the doses

MTX ≥ 15/MTX other: methotrexate ≥ 15 mg per week/methotrexate < 15 mg per week; ALEFACEPT: alefacept all dosages; CICLO High: ciclosporin ≥ 3 mg/kg/day; ACI ≥ 35: acitretin ≥ 35 mg per day; FUM: fumaric acid esters all dosages; APRE 30: apremilast 30 mg twice daily; PONE 40: ponesimod 40 mg per day; TOFA 20: tofacitinib 20 mg per day; ETA 25/ETA 50: etanercept 25 mg twice a week/etanercept 50 mg twice a week; IFX: infliximab 5 mg/kg week O, 2, 4 every 6 weeks; ADA: adalimumab 80 mg Week 0, 40 mg Week 1 then 40 mg every other week; CERTO 200/400: certolizumab all dosages; USK 45: ustekinumab 45 mg; SECU 300/SECU other: secukinumab 300 mg every injection/secukinumab other dosages; IXE 200/IXE other: ixekizumab 200 mg per injection/ixekizumab other dosages; TILDRA 100/200: tildrakizumab all dosages; GUSEL 100: guselkumab 100 mg per injection; BRODA 210: brodalumab 210 mg per injection

CI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio; SAE: serious adverse events

Sensitivity analyses ‐ Interval plot. Network meta‐analysis results for primary outcomes (PASI 90 and serious adverse events) for all the interventions excluding studies at high risk of bias. ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumabCI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio; SAE: serious adverse events
Figuras y tablas -
Figure 30

Sensitivity analyses ‐ Interval plot. Network meta‐analysis results for primary outcomes (PASI 90 and serious adverse events) for all the interventions excluding studies at high risk of bias.

ACI: acitretin; ADA: adalimumab; APRE: apremilast; BRODA: brodalumab; CERTO: certolizumab; CICLO: ciclosporin; ETA: etanercept; FUM: fumaric acid; IFX: infliximab; ITO: itolizumab; IXE: ixekizumab; GUSEL: guselkumab; MTX: methotrexate; PBO: placebo; PONE: ponesimod; SECU: secukinumab; TILDRA: tildrakizumab; TOFA: tofacitinib; USK: ustekinumab

CI: confidence interval; PASI: Psoriasis Area and Severity Index; RR: risk ratio; SAE: serious adverse events

Funnel plot for network meta‐analysis of all the outcomes AE: adverse event; lnRR: Mean effect size; PASI: Psoriasis Area and Severity Index; QoL: Specific quality of life scale; RR: Risk ratio; SAE: serious adverse events; SMD: standardised mean difference
Figuras y tablas -
Figure 31

Funnel plot for network meta‐analysis of all the outcomes

AE: adverse event; lnRR: Mean effect size; PASI: Psoriasis Area and Severity Index; QoL: Specific quality of life scale; RR: Risk ratio; SAE: serious adverse events; SMD: standardised mean difference

Study bias distribution for each primary outcome (PASI 90 and serious adverse events) The following graphs show how much information (i.e. the percentage contribution of each direct comparison in the network estimates) comes from low (green), unclear/moderate (yellow) and high (red) risk of bias studies. Here we have all drugs versus placebo as it is difficult to have all comparisons due to space limitations. To evaluate the direct comparisons we used the mean level of bias of the included studies in each comparison.We used the web application CINeMA (CINeMA 2017).The codes of the treatments are A = Placebo, B = Fumaric acid esters, C = Methotrexate, D = Acitretin, E = Alefacept, F = Ciclosporin, G = Infliximab, H = Adalimumab, I = Etanercept, J = Ustekinumab, K = Secukinumab, L = Ixekizumab, M = Brodalumab, N = Certolizumab, O = Apremilast, P = Tofacitinib, Q = Guselkumab, R = Tildrakizumab, S = Ponesimod, T = Itolizumab
Figuras y tablas -
Figure 32

Study bias distribution for each primary outcome (PASI 90 and serious adverse events)

The following graphs show how much information (i.e. the percentage contribution of each direct comparison in the network estimates) comes from low (green), unclear/moderate (yellow) and high (red) risk of bias studies. Here we have all drugs versus placebo as it is difficult to have all comparisons due to space limitations. To evaluate the direct comparisons we used the mean level of bias of the included studies in each comparison.

We used the web application CINeMA (CINeMA 2017).

The codes of the treatments are A = Placebo, B = Fumaric acid esters, C = Methotrexate, D = Acitretin, E = Alefacept, F = Ciclosporin, G = Infliximab, H = Adalimumab, I = Etanercept, J = Ustekinumab, K = Secukinumab, L = Ixekizumab, M = Brodalumab, N = Certolizumab, O = Apremilast, P = Tofacitinib, Q = Guselkumab, R = Tildrakizumab, S = Ponesimod, T = Itolizumab

Comparison 1 Primary outcome ‐ PASI 90, Outcome 1 Conventional systemic agents versus placebo.
Figuras y tablas -
Analysis 1.1

Comparison 1 Primary outcome ‐ PASI 90, Outcome 1 Conventional systemic agents versus placebo.

Comparison 1 Primary outcome ‐ PASI 90, Outcome 2 Conventional systemic 1 versus conventional systemic 2.
Figuras y tablas -
Analysis 1.2

Comparison 1 Primary outcome ‐ PASI 90, Outcome 2 Conventional systemic 1 versus conventional systemic 2.

Comparison 1 Primary outcome ‐ PASI 90, Outcome 3 Anti‐TNF alpha versus placebo.
Figuras y tablas -
Analysis 1.3

Comparison 1 Primary outcome ‐ PASI 90, Outcome 3 Anti‐TNF alpha versus placebo.

Comparison 1 Primary outcome ‐ PASI 90, Outcome 4 Ustekinumab versus placebo.
Figuras y tablas -
Analysis 1.4

Comparison 1 Primary outcome ‐ PASI 90, Outcome 4 Ustekinumab versus placebo.

Comparison 1 Primary outcome ‐ PASI 90, Outcome 5 Anti‐IL17 versus placebo.
Figuras y tablas -
Analysis 1.5

Comparison 1 Primary outcome ‐ PASI 90, Outcome 5 Anti‐IL17 versus placebo.

Comparison 1 Primary outcome ‐ PASI 90, Outcome 6 Anti‐IL23 versus placebo.
Figuras y tablas -
Analysis 1.6

Comparison 1 Primary outcome ‐ PASI 90, Outcome 6 Anti‐IL23 versus placebo.

Comparison 1 Primary outcome ‐ PASI 90, Outcome 7 Other biologics.
Figuras y tablas -
Analysis 1.7

Comparison 1 Primary outcome ‐ PASI 90, Outcome 7 Other biologics.

Comparison 1 Primary outcome ‐ PASI 90, Outcome 8 Biologic versus conventional systemic treatments.
Figuras y tablas -
Analysis 1.8

Comparison 1 Primary outcome ‐ PASI 90, Outcome 8 Biologic versus conventional systemic treatments.

Comparison 1 Primary outcome ‐ PASI 90, Outcome 9 Biologic 1 versus biologic 2.
Figuras y tablas -
Analysis 1.9

Comparison 1 Primary outcome ‐ PASI 90, Outcome 9 Biologic 1 versus biologic 2.

Comparison 1 Primary outcome ‐ PASI 90, Outcome 10 Small molecules versus placebo.
Figuras y tablas -
Analysis 1.10

Comparison 1 Primary outcome ‐ PASI 90, Outcome 10 Small molecules versus placebo.

Comparison 1 Primary outcome ‐ PASI 90, Outcome 11 Biologic versus small molecules.
Figuras y tablas -
Analysis 1.11

Comparison 1 Primary outcome ‐ PASI 90, Outcome 11 Biologic versus small molecules.

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 1 Conventional systemic agents versus placebo.
Figuras y tablas -
Analysis 2.1

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 1 Conventional systemic agents versus placebo.

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 2 Anti‐TNF alpha versus placebo.
Figuras y tablas -
Analysis 2.2

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 2 Anti‐TNF alpha versus placebo.

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 3 Ustekinumab versus placebo.
Figuras y tablas -
Analysis 2.3

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 3 Ustekinumab versus placebo.

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 4 Anti‐IL17 versus placebo.
Figuras y tablas -
Analysis 2.4

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 4 Anti‐IL17 versus placebo.

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 5 Anti‐IL23 versus placebo.
Figuras y tablas -
Analysis 2.5

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 5 Anti‐IL23 versus placebo.

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 6 Other biologics.
Figuras y tablas -
Analysis 2.6

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 6 Other biologics.

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 7 Biologic versus conventional systemic treatments.
Figuras y tablas -
Analysis 2.7

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 7 Biologic versus conventional systemic treatments.

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 8 Biologic 1 versus biologic 2.
Figuras y tablas -
Analysis 2.8

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 8 Biologic 1 versus biologic 2.

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 9 Small molecules versus placebo.
Figuras y tablas -
Analysis 2.9

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 9 Small molecules versus placebo.

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 10 Biologic versus small molecules.
Figuras y tablas -
Analysis 2.10

Comparison 2 Primary outcome ‐ serious adverse events, Outcome 10 Biologic versus small molecules.

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 1 Conventional systemic agents versus placebo.
Figuras y tablas -
Analysis 3.1

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 1 Conventional systemic agents versus placebo.

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 2 Conventional systemic 1 versus conventional systemic 2.
Figuras y tablas -
Analysis 3.2

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 2 Conventional systemic 1 versus conventional systemic 2.

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 3 Anti‐TNF alpha versus placebo.
Figuras y tablas -
Analysis 3.3

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 3 Anti‐TNF alpha versus placebo.

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 4 Ustekinumab versus placebo.
Figuras y tablas -
Analysis 3.4

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 4 Ustekinumab versus placebo.

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 5 Anti‐IL17 versus placebo.
Figuras y tablas -
Analysis 3.5

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 5 Anti‐IL17 versus placebo.

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 6 Anti‐IL23 versus placebo.
Figuras y tablas -
Analysis 3.6

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 6 Anti‐IL23 versus placebo.

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 7 Other biologics.
Figuras y tablas -
Analysis 3.7

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 7 Other biologics.

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 8 Biologic versus conventional systemic treatments.
Figuras y tablas -
Analysis 3.8

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 8 Biologic versus conventional systemic treatments.

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 9 Biologic 1 versus biologic 2.
Figuras y tablas -
Analysis 3.9

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 9 Biologic 1 versus biologic 2.

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 10 Small molecules versus placebo.
Figuras y tablas -
Analysis 3.10

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 10 Small molecules versus placebo.

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 11 Biologic versus small molecules.
Figuras y tablas -
Analysis 3.11

Comparison 3 Secondary outcome ‐ PASI 75, Outcome 11 Biologic versus small molecules.

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 1 Conventional systemic agents versus placebo.
Figuras y tablas -
Analysis 4.1

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 1 Conventional systemic agents versus placebo.

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 2 Conventional systemic 1 versus conventional systemic 2.
Figuras y tablas -
Analysis 4.2

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 2 Conventional systemic 1 versus conventional systemic 2.

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 3 Anti‐TNF alpha versus placebo.
Figuras y tablas -
Analysis 4.3

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 3 Anti‐TNF alpha versus placebo.

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 4 Ustekinumab versus placebo.
Figuras y tablas -
Analysis 4.4

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 4 Ustekinumab versus placebo.

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 5 Anti‐IL17 versus placebo.
Figuras y tablas -
Analysis 4.5

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 5 Anti‐IL17 versus placebo.

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 6 Anti‐IL23 versus placebo.
Figuras y tablas -
Analysis 4.6

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 6 Anti‐IL23 versus placebo.

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 7 Other biologics.
Figuras y tablas -
Analysis 4.7

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 7 Other biologics.

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 8 Biologic versus conventional systemic treatments.
Figuras y tablas -
Analysis 4.8

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 8 Biologic versus conventional systemic treatments.

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 9 Biologic 1 versus biologic 2.
Figuras y tablas -
Analysis 4.9

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 9 Biologic 1 versus biologic 2.

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 10 Small molecules versus placebo.
Figuras y tablas -
Analysis 4.10

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 10 Small molecules versus placebo.

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 11 Biologic versus small molecules.
Figuras y tablas -
Analysis 4.11

Comparison 4 Secondary outcome ‐ PGA 0/1, Outcome 11 Biologic versus small molecules.

Comparison 5 Secondary outcome ‐ quality of life, Outcome 1 Conventional systemic agents versus placebo.
Figuras y tablas -
Analysis 5.1

Comparison 5 Secondary outcome ‐ quality of life, Outcome 1 Conventional systemic agents versus placebo.

Comparison 5 Secondary outcome ‐ quality of life, Outcome 2 Anti‐TNF alpha versus placebo.
Figuras y tablas -
Analysis 5.2

Comparison 5 Secondary outcome ‐ quality of life, Outcome 2 Anti‐TNF alpha versus placebo.

Comparison 5 Secondary outcome ‐ quality of life, Outcome 3 Ustekinumab versus placebo.
Figuras y tablas -
Analysis 5.3

Comparison 5 Secondary outcome ‐ quality of life, Outcome 3 Ustekinumab versus placebo.

Comparison 5 Secondary outcome ‐ quality of life, Outcome 4 Anti‐IL17 versus placebo.
Figuras y tablas -
Analysis 5.4

Comparison 5 Secondary outcome ‐ quality of life, Outcome 4 Anti‐IL17 versus placebo.

Comparison 5 Secondary outcome ‐ quality of life, Outcome 5 Anti‐IL23 versus placebo.
Figuras y tablas -
Analysis 5.5

Comparison 5 Secondary outcome ‐ quality of life, Outcome 5 Anti‐IL23 versus placebo.

Comparison 5 Secondary outcome ‐ quality of life, Outcome 6 Other biologics.
Figuras y tablas -
Analysis 5.6

Comparison 5 Secondary outcome ‐ quality of life, Outcome 6 Other biologics.

Comparison 5 Secondary outcome ‐ quality of life, Outcome 7 Biologic versus conventional systemic treatments.
Figuras y tablas -
Analysis 5.7

Comparison 5 Secondary outcome ‐ quality of life, Outcome 7 Biologic versus conventional systemic treatments.

Comparison 5 Secondary outcome ‐ quality of life, Outcome 8 Biologic 1 versus biologic 2.
Figuras y tablas -
Analysis 5.8

Comparison 5 Secondary outcome ‐ quality of life, Outcome 8 Biologic 1 versus biologic 2.

Comparison 5 Secondary outcome ‐ quality of life, Outcome 9 Small molecules versus placebo.
Figuras y tablas -
Analysis 5.9

Comparison 5 Secondary outcome ‐ quality of life, Outcome 9 Small molecules versus placebo.

Comparison 5 Secondary outcome ‐ quality of life, Outcome 10 Biologic versus small molecules.
Figuras y tablas -
Analysis 5.10

Comparison 5 Secondary outcome ‐ quality of life, Outcome 10 Biologic versus small molecules.

Comparison 6 Secondary outcome ‐ adverse events, Outcome 1 Conventional systemic agents versus placebo.
Figuras y tablas -
Analysis 6.1

Comparison 6 Secondary outcome ‐ adverse events, Outcome 1 Conventional systemic agents versus placebo.

Comparison 6 Secondary outcome ‐ adverse events, Outcome 2 Conventional systemic 1 versus conventional systemic 2.
Figuras y tablas -
Analysis 6.2

Comparison 6 Secondary outcome ‐ adverse events, Outcome 2 Conventional systemic 1 versus conventional systemic 2.

Comparison 6 Secondary outcome ‐ adverse events, Outcome 3 Anti‐TNF alpha versus placebo.
Figuras y tablas -
Analysis 6.3

Comparison 6 Secondary outcome ‐ adverse events, Outcome 3 Anti‐TNF alpha versus placebo.

Comparison 6 Secondary outcome ‐ adverse events, Outcome 4 Ustekinumab versus placebo.
Figuras y tablas -
Analysis 6.4

Comparison 6 Secondary outcome ‐ adverse events, Outcome 4 Ustekinumab versus placebo.

Comparison 6 Secondary outcome ‐ adverse events, Outcome 5 Anti‐IL17 versus placebo.
Figuras y tablas -
Analysis 6.5

Comparison 6 Secondary outcome ‐ adverse events, Outcome 5 Anti‐IL17 versus placebo.

Comparison 6 Secondary outcome ‐ adverse events, Outcome 6 Anti‐IL23 versus placebo.
Figuras y tablas -
Analysis 6.6

Comparison 6 Secondary outcome ‐ adverse events, Outcome 6 Anti‐IL23 versus placebo.

Comparison 6 Secondary outcome ‐ adverse events, Outcome 7 Biologic versus conventional systemic treatments.
Figuras y tablas -
Analysis 6.7

Comparison 6 Secondary outcome ‐ adverse events, Outcome 7 Biologic versus conventional systemic treatments.

Comparison 6 Secondary outcome ‐ adverse events, Outcome 8 Biologic 1 versus biologic 2.
Figuras y tablas -
Analysis 6.8

Comparison 6 Secondary outcome ‐ adverse events, Outcome 8 Biologic 1 versus biologic 2.

Comparison 6 Secondary outcome ‐ adverse events, Outcome 9 Small molecules versus placebo.
Figuras y tablas -
Analysis 6.9

Comparison 6 Secondary outcome ‐ adverse events, Outcome 9 Small molecules versus placebo.

Comparison 6 Secondary outcome ‐ adverse events, Outcome 10 Biologic versus small molecules.
Figuras y tablas -
Analysis 6.10

Comparison 6 Secondary outcome ‐ adverse events, Outcome 10 Biologic versus small molecules.

Summary of findings for the main comparison. Any systemic treatment compared to placebo for chronic plaque psoriasis

Any systemic treatment compared to placebo for chronic plaque psoriasis (network meta‐analysis)

Patient or population: people with chronic plaque psoriasis
Intervention: any systemic treatment
Comparison: placebo

Setting: all the participants were recruited from a hospital setting

Timescale: 12 to 16 weeks after randomisation

Intervention

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

SUCRA

№ of participants
(studies)b

Certainty of the evidence
(GRADE)

Comments

Risk with placeboa

Risk with any systemic treatment

PASI 90

Ixekizumab

Moderate

RR 32.45
(23.61 to 44.60)

94.3

3268
(4 RCTs)

⊕⊕⊕⊕
High

15 per 1000

487 per 1000
(354 to 669)

Secukinumab

Moderate

RR 26.55
(20.32 to 34.69)

86.5

2707
(7 RCTs)

⊕⊕⊕⊕
High

15 per 1000

398 per 1000
(305 to 520)

Brodalumab

Moderate

RR 25.45
(18.74 to 34.57)

84.3

4109
(5 RCTs)

⊕⊕⊕⊝
Moderate

Reasons for downgrading by one level: three studies contributing to this estimate at high risk of bias in selective reporting domain

15 per 1000

382 per 1000
(281 to 520)

Guselkumab

Moderate

RR 21.03
(14.56 to 30.38)

77

1502
(3 RCTs)

⊕⊕⊕⊝
Moderate

Reasons for downgrading by one level: one study contributing to this estimate at high risk of bias in selective reporting domain

15 per 1000

315 per 1000
(218 to 456)

Certolizumab

Moderate

RR 24.58
(3.46 to 174.73)

75.7

176
(1 RCT)

⊕⊕⊕⊝
Moderate

Downgraded one level due to imprecision: wide CIs

15 per 1000

369 per 1000
(52 to 1000)

Ustekinumab

Moderate

RR 19.91
(15.11 to 26.23)

72.6

3832
(7 RCTs)

⊕⊕⊕⊕
High

15 per 1000

299 per 1000
(227 to 393)

Tildrakizumab

Moderate

RR 15.63
(2.22 to 110.07)

63.6

355
(1 RCT)

⊕⊕⊝⊝
Low

Downgraded one level due to risk of bias and one level due to imprecision. The single study contributing to this estimate at unclear risk of bias in both blinding domains; wide CIs

15 per 1000

234 per 1000
(33 to 1000)

Adalimumab

Moderate

RR 14.87
(10.45 to 21.14)

63.1

3199
(8 RCTs)

⊕⊕⊕⊝
Moderate

Downgraded one level due to inconsistency ‐ inconsistent loops of evidence

15 per 1000

223 per 1000
(157 to 317)

Itolizumab

Moderate

RR 12.26
(0.76 to 198.53)

56

225
(1 RCT)

⊕⊕⊝⊝
Low

Downgraded one level due to imprecision (wide CIs) and one level due to risk of bias (moderate risk using credibility of evidence)

15 per 1000

184 per 1000
(12 to 1000)

Infliximab

Moderate

RR 11.18
(5.67 to 22.04)

53.2

(0 RCTs)

⊕⊝⊝⊝
Very low

Downgraded one level due to risk of bias (credibility of risk), one level due to imprecision (wide CIs) and one level due to inconsistency (inconsistent loop of evidence)

15 per 1000

168 per 1000
(85 to 331)

Etanercept

Moderate

RR 10.79
(8.47 to 13.73)

52.6

4954
(12 RCTs)

⊕⊕⊕⊝
Moderate

Downgraded one level due to inconsistency (global inconsistency ‐ side‐splitting approach)

15 per 1000

162 per 1000
(127 to 206)

Tofacitinib

Moderate

RR 8.50
(6.23 to 11.60)

42.5

2826
(4 RCTs)

⊕⊕⊝⊝
Low

Downgraded one level due to risk of bias: two studies at high risk of bias in incomplete outcome data domain; and downgraded one level due to inconsistency (global approach)

15 per 1000

128 per 1 000
(93 to 174)

Apremilast

Moderate

RR 7.66
(4.30 to 13.66)

39.7

1775
(4 RCTs)

⊕⊕⊕⊝
Moderate

Downgraded one level due to risk of bias: one study had a slight risk of bias in selective reporting domain

15 per 1000

115 per 1000
(65 to 205)

Ponesimod

Moderate

RR 6.60
(1.63 to 26.67)

37.3

326
(1 RCT)

⊕⊕⊕⊝
Moderate

Downgraded one level due to imprecision: wide CIs

15 per 1000

99 per 1000
(24 to 400)

Alefacept

Moderate

RR 4.39
(1.38 to 13.94)

25.3

(0 RCTs)

⊕⊝⊝⊝
Very low

Downgraded two levels due to risk of bias and a further one level due to imprecision ‐ study indirectly contributing to the estimates at high risk of bias in selective reporting domain; wide CIs

15 per 1000

66 per 1000
(21 to 209)

Fumaric acid esters (FAEs)

Moderate

RR 4.09
(1.88 to 8.88)

21.9

704
(1 RCT)

⊕⊝⊝⊝
Very low

Downgraded two levels due to risk of bias, and one level due to imprecision ‐ the studies indirectly contributing to this estimate at high risk of bias in blinding domain; wide CIs

15 per 1000

61 per 1000
(28 to 133)

Ciclosporin

Moderate

RR 3.99
(1.81 to 8.78)

21.3

(0 RCTs)

⊕⊝⊝⊝
Very low

Downgraded two levels due to risk of bias, and a further one level due to imprecision ‐ the single study indirectly contributing to this estimate at high risk of bias in blinding; wide CIs

15 per 1000

60 per 1000
(27 to 132)

Methotrexate

Moderate

RR 3.61
(2.01 to 6.48)

20.2

282
(2 RCTs)

⊕⊕⊕⊝
Moderate

Downgraded one level due to inconsistency (inconsistent loop of evidence)

15 per 1000

59 per 1000
(32 to 106)

Acitretin

Moderate

RR 0.98
(0.06 to 17.24)

9.9

(0 RCTs)

⊕⊝⊝⊝
Very low

Downgraded two levels due to risk of bias and a further one level due to imprecision. The single study contributing to this estimate at high risk of bias in incomplete outcome data and blinding domains; wide CIs

15 per 1000

15 per 1000
(1 to 259)

Serious adverse events

Methotrexate

Moderate

RR 0.23
(0.05 to 0.99)

90.7

282
(2 RCTs)

⊕⊕⊕⊝
Moderate

Downgraded one level due to imprecision (wide CIs)

17 per 1000

4 per 1000
(1 to 17)

Ciclosporin

Moderate

RR 0.23
(0.01 to 5.10)

78.2

(0 RCTs)

⊕⊝⊝⊝
Very low

Downgraded two levels due to risk of bias (credibility of evidence), and one level due to imprecision (wide CIs)

17 per 1000

4 per 1000
(0 to 87)

Certolizumab

Moderate

RR 0.49
(0.10 to 2.36)

70.9

176
(1 RCT)

⊕⊕⊕⊝
Moderate

Downgraded one level due to imprecision (wide CIs)

17 per 1000

8 per 1000
(2 to 40)

Infliximab

Moderate

RR 0.56
(0.10 to 3.00)

64.4

(0 RCTs)

⊕⊝⊝⊝
Very low

Downgraded two levels due to risk of bias, and one level due to imprecision: credibility of evidence; wide CIs

17 per 1000

10 per 1000
(2 to 51)

Alefacept

Moderate

RR 0.72
(0.34 to 1.55)

62.6

736
(2 RCTs)

⊕⊕⊝⊝
Low

Downgraded one level due to risk of bias (credibility of evidence), and one level due to imprecision (wide CIs)

17 per 1000

12 per 1000
(6 to 26)

Fumaric acid esters (FAEs)

Moderate

RR 0.77
(0.30 to 2.00)

57.7

704
(1 RCT)

⊕⊝⊝⊝
Very low

Downgraded by one level due to risk of bias and one level due to imprecision: credibility of evidence; wide CIs

17 per 1000

13 per 1000
(5 to 34)

Apremilast

Moderate

RR 0.84
(0.47 to 1.51)

54.7

2036
(5 RCTs)

⊕⊕⊝⊝
Low

Downgraded one level due to risk of bias and one level due to imprecision: credibility of evidence and wide CIs

17 per 1000

14 per 1000
(8 to 26)

Ustekinumab

Moderate

RR 0.89
(0.57 to 1.39)

52

4154
(8 RCTs)

⊕⊕⊝⊝
Low

Downgraded one level due to risk of bias and one level due to imprecision ‐ credibility of evidence; wide CIs

17 per 1000

15 per 1000
(10 to 24)

Acitretin

Moderate

RR 0.99
(0.02 to 49.37)

46.9

(0 RCTs)

⊕⊝⊝⊝
Very low

Downgraded by two levels due to risk of bias and one level due to imprecision: credibility of evidence; wide CIs

17 per 1000

17 per 1000
(0 to 839)

Tofacitinib

Moderate

RR 0.98
(0.55 to 1.76)

44

2838
(5 RCTs)

⊕⊕⊕⊝
Moderate

Downgraded one level due to imprecision (wide CIs)

17 per 1000

17 per 1000
(9 to 30)

Etanercept

Moderate

RR 0.99
(0.65 to 1.51)

43.6

3783
(11 RCTs)

⊕⊕⊕⊝
Moderate

Downgraded one level due to imprecision (CIs including one)

17 per 1000

17 per  1000
(11 to 26)

Guselkumab

Moderate

RR 1.00
(0.49 to 2.04)

42.6

1502
(3 RCTs)

⊕⊕⊝⊝
Low

Downgraded one level due to risk of bias (credibility of evidence), and one level due to imprecision (CIs including one)

15 per 1000

15 per 1000
(7 to 31)

Adalimumab

Moderate

RR 1.02
(0.61 to 1.73)

40.4

3199
(8 RCTs)

⊕⊕⊕⊝
Moderate

Downgraded one level due to imprecision (CIs including one)

18 per 1000

19 per 1000
(11 to 31)

Brodalumab

Moderate

RR 1.04
(0.62 to 1.73)

39.8

4109
(5 RCTs)

⊕⊕⊝⊝
Low

Downgraded one level due to risk of bias (credibility of evidence) and one level due to imprecision (CIs including 1)

17 per 1000

18 per 1000
(11 to 30)

Tildrakizumab

Moderate

RR 1.36
(0.07 to 24.94)

37.8

355
(1 RCT)

⊕⊕⊝⊝
Low

Downgraded one level due to risk of bias (credibility of evidence) and one level due to imprecision (CIs including 1)

0 per 1000

0 per 1000
(0 to 0)

Ixekizumab

Moderate

RR 1.12
(0.66 to 1.90)

33.7

3268
(4 RCTs)

⊕⊕⊕⊝
Moderate

Downgraded one level due to imprecision (CIs including one)

15 per 1000

16 per 1000
(10 to 28)

Secukinumab

Moderate

RR 1.19
(0.69 to 2.03)

29.9

2707
(7 RCTs)

⊕⊕⊕⊝
Moderate

Downgraded one level due to imprecision (CIs including one)

10 per 1000

12 per 1000
(7 to 20)

Ponesimod

Moderate

RR 2.59
(0.34 to 19.85)

18.1

326
(1 RCT)

⊕⊕⊕⊝
Moderate

Downgraded one level due to imprecision (CIs including one)

15 per 1000

39 per 1000
(5 to 296)

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: confidence interval; PASIc: Psoriasis Area and Severity Index; RR: risk ratio; SUCRAd: Surface Under the Cumulative Ranking

GRADE Working Group grades of evidence
High certainty/quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty/quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low certainty/quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty/quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

a 'Risk with placebo' is the median placebo‐group risk value in the included studies for the assumed risk with placebo.
b 'Number of studies (participants)' is from the direct comparisons.

c The Psoriasis Area and Severity Index combines the assessment of the severity of lesions and the area affected into a single score in the range of 0 (no disease) to 72 (maximal disease); PASI 90: 90% improvement in the PASI.

d SUCRA was expressed as a percentage between 0 (when a treatment is certain to be the worst) to 100% (when a treatment is certain to be the best).

Figuras y tablas -
Summary of findings for the main comparison. Any systemic treatment compared to placebo for chronic plaque psoriasis
Table 1. Glossary

Term

Definition

Antagonist

A substance that interferes with or inhibits the physiological action of another.

Antigen

A molecule capable of inducing an immune respons

Anti‐TNF alpha

A pharmaceutical drug that suppresses the physiologic response to tumor necorsis factor (TNF)

Biological agent

Therapeutic agents consisting of immune molecules such as soluble receptors, recombinant cytokines, and monoclonal antibodies that target effector molecules or cells of the immune system

CD6

Cluster of differentiation (CD) 6 is a protein encoded by the CD6 gene

Cheilitis

An inflammation of the lips

Chimeric protein

A chimeric protein can be made by combining two different genes

Complex cyclophilin‐ciclosporin

Cyclophilins are a family of proteins that bind to ciclosporin, an immunosuppressant agent

Creatinine

A compound that is produced by metabolism of creatine and excreted in the urine

Cyclic adenosine monophosphate

It is a second messenger important in many biological processes

Cytokines

Small proteins produced by a broad range of cells that are important in cell signaling; they are immunomodulating agents

Dendritic cells

Antigen‐presenting cells of the immune system

Dermis

It is a layer of the skin

Epitope

It is a part of an antigen

Erythematous

Redness of the skin

Folic acid

B vitamin

Humanised antibody

Antibodies from non‐human species whose protein sequences have been modified to increase their similarity to antibody variants produced naturally in humans

IL‐17A

A pro‐inflammatory cytokine

IL‐23R

A cytokine receptor

Immune‐mediated

A group of diseases that are characterised by common inflammatory pathways leading to inflammation, and which may result from a dysregulation of the normal immune response

Immunogenicity

This is the ability of a particular substance, such as an antigen or epitope, to provoke an immune response in the body of a human or animal

Immunoglobulin 1 Fc

An antibody

Interferon (IFN)‐c

A protein released by cells, usually in response to a pathogen

Interleukin

A kind of cytokine

Janus kinase (JAK) inhibitors

A pharmaceutical drug that inhibits the activity of one or more of the Janus kinase family of enzymes

Keratinocytes

Epidermal cells that constitute 95% of the epidermis

Lymphocyte

A subtype of a white blood cell

Lymphoid organ

Part of the body that defends the body against invading pathogens that cause infections or the spread of tumours

Metalloproteinases

A protease enzyme

Monoclonal antibodies

Antibodies that are made by identical immune cells that are all clones of a unique parent cell

Murine sequence

Mouse genomic sequencing

Neutrophils

Type of white blood cell involved in the innate immune system

p40

Subunit beta of interleukin 12 and 23

Periumbilical

Around the navel

Pharmacological treatments

Drugs

Phase I

First‐in‐man studies

Phase II

Studies to assess how well the drug works, as well as to continue phase I safety assessments in a larger group of volunteers and participants

Phase III

Randomised controlled multicenter trials on large patient groups and are aimed at being the definitive assessment of how effective the drug is

Phase IV

Post‐marketing trials involve the safety surveillance

Phosphodiesterase 4 inhibitors

A pharmaceutical drug used to block the degradative action of phosphodiesterase 4

Progressive multifocal leukoencephalopathy

A rare viral neurological disease characterised by progressive damage of the white matter of the brain at multiple locations

Receptor

A protein molecule that receives chemical signals from outside a cell

Small molecules

Chemically manufactured molecules (or SMOLs for short)

Sphingosine 1‐phosphate receptor agonists

A class of protein‐coupled receptors that are targets of the lipid signalling molecule Sphingosine‐1‐phosphate

T cells/CD4 T cells

A type of white blood cell that is of key importance to the immune system

Th1 and Tc1 cells

A type of T cell

Th17 and Tc17 cells

A type of T cell

TNF‐alpha

A protein that is part of the inflammatory response

Tumour necrosis factor antagonists

Class of biological agents

Umbilic

Navel

Xerosis

Dry skin

Figuras y tablas -
Table 1. Glossary
Table 2. Investigators contacted

Contact

Requested Information

Contacted

Reply (last check 1/03/2017)

Missing data

Akcali 2014

Prof. Akcali

Outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

8 and 21 November 2016

No response

Al‐Hamamy 2014

Prof. Al‐Hamamy

Outcomes: PASI 75, PGA 0/1, QoL scale, AEs & SAEs

8 and 21 November 2016

No response

Asahina 2010

Prof. Asahina

Outcome: PASI 90

8 November 2016

Asahina 2010 detailed report

Asahina 2016

Prof. Asahina Pfizer

Outcomes: AEs & SAEs

3 and 12 January 2017

Additional data to the publication not provided

Asawanonda 2006

Prof. Asawanonda

Outcomes: PASI 75, PGA 0/1, AEs & SAEs

21 November 2016

15 December 2016

Asawanonda 2006 sent detailed report for PASI 75 and AEs. PGA was not collected during this study.

Bissonnette 2015

Prof. Bisonnette Innovaderm Recherches Inc.

Outcomes: PASI 90, PGA 0/1, AEs

8 and 21 November 2016

Additional data to the publication not provided

Blauvelt FEATURE, 2015

Dr Blauvelt

Novartis

Outcome: QoL scale

8 and 21 November 2016

Additional data to the publication not provided

Caproni 2009

Prof. Fabri

Outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

8 and 21 November 2016

Caproni 2009 sent detailed report for PASI 90 and SAEs. Other outcomes (PGA, QoL and AEs) not collected during this study.

Dogra 2013

Prof. Dogra

Outcomes: PGA 0/1, QoL scale, AEs & SAEs

8 and 21 November 2016

No response

Dogra 2012

Prof. Dogra

Outcomes: PGA 0/1, QoL scale, AEs & SAEs

8 November 2016

PGA & QoL scale not collected during this study. AEs & SAEs not provided per arm

Fallah Arani 2011

Dr Fallah Arani

Outcomes: PASI 90, PGA 0/1 and QoL scale

8 and 21 November 2016

Outcomes not collected during this study

Flytström 2008

Prof. Flytstrom

Outcomes: PGA 0/1

12 and 19 January 2017

Additional data to the publication not provided

Gisondi 2008

Prof. Gisondi

Outcomes: PASI 90, PGA 0/1, QoL scale, AEs & SAEs

8 November 2016

Gisondi 2008 sent detailed report for the requested outcomes except for QoL (not assessed during the study)

Gordon 2006

Prof. Gordon

Outcomes: PGA0/1, AEs

3 and 12 January 2017

No response

Gottlieb 2012

Prof. Gottlieb

Abbvie

Outcomes: PASI 90 & QoL scale

8 November 2016

Gottlieb 2012 sent detailed report for the requested outcomes

Gottlieb 2011

Prof. Gottlieb

Amgen

Outcomes: PASI 90, PGA 0/1, QoL scale, AEs & SAEs

8 November 2016

Gottlieb 2011 sent detailed report for the requested outcomes

Griffiths ACCEPT, 2010

Prof. Griffiths

Janssen

Outcome: QoL scale

16 December 2016

QoL was not collected during this study

Jacobe 2008

Prof. Jacobe

Outcomes: PASI 90, PGA 0/1, QoL scale, AEs & SAEs

8 and 20 November 2016

No response

Krueger 2016

Pfizer

Outcomes: PASI 90, QoL scale

3 and 12 January 2017

No response

Krupashankar 2014

Prof. Ganapathi

R&D, Biocon Research Limited

Outcomes: QoL scale, AEs & SAEs

8 and 21 November 2016

Krupashandar sent detailed report for the requested outcomes, however AEs and SAEs were only available for the entire trial and not at the time of the major outcome assessment

Lebwohl AMAGINE‐2, 2015

Prof. Lebwohl

Valeant Pharmaceuticals NA LLC

Outcomes: PASI 90 & QoL scale

8 and 21 November 2016

Lebwohl AMAGINE‐2, 2015 sent detailed report for PASI 90, individual scores and median difference from baseline of QoL were not available

Lebwohl AMAGINE‐3, 2015

Prof. Lebwohl

Valeant Pharmaceuticals NA LLC

Outcomes: PASI 90 & QoL scale

8 and 21 November 2016

Lebwohl AMAGINE‐3, 2015 sent detailed report for PASI 90, individual scores and median difference from baseline of QoL were not available

Leonardi 2012

Prof. Leonardi

Outcomes: QoL scale & AEs

8 and 21 November 2016

No response

Mahajan 2010

Prof. Kaur

Outcomes: PASI 90, PGA 0/1, QoL scale, AEs & SAEs

8 and 21 November 2016

No response

Menter REVEAL, 2008

Prof. Menter

Outcome: PGA 0/1

8 and 21 November 2016

No response

Menter EXPRESS‐II, 2007

Prof. Menter

Outcome: PGA 0/1

8 and 21 November 2016

No response

Mrowietz BRIDGE, 2016

Prof. Mrowietz

Outcome: QoL scale

3 and 12 January 2017

Additional data to the publication not provided

Ortonne 2013

Prof. Paul

Novartis

Outcome: PASI 90

3 January 2017

Additional data to the publication not provided

Papp 2013a

Prof. Papp

Outcome: QoL scale

22 November 2016 13 December 2016

Additional data to the publication not provided

Papp AMAGINE‐1, 2016

Prof. Papp

Outcome: QoL scale

22 November 2016 13 December 2016

Additional data to the publication not provided

Papp 2005

Prof. Papp

Outcome: QoL scale, AEs & SAEs

22 November 2016 13 December 2016

Additional data to the publication not provided

Papp 2012a

Prof. Papp

Outcome: QoL scale

22 November 2016 13 December 2016

Additional data to the publication not provided

Papp 2013b

Prof. Papp

Outcome: PASI 90, PGA0/1, QoL scale

3 January 2017

Additional data to the publication not provided

Paul JUNCTURE, 2015

Prof. Paul

Novartis

Outcome: QoL scale

15 December 2016, 2 January 2017

Additional data to the publication not provided

Reich 2015

Prof. Reich

Novartis

Outcomes: PGA 0/1 & QoL scale

8 November 2016, 16 December 2016

Additional data to the publication not provided

Reich LIBERATE, 2017

Prof. Reich PelotonAdvantage

Outcome: QoL scale

4 January 2017

Additional data to the publication not provided

Rich 2013

Prof. Rich

Outcome: QoL scale

22 November 2016, 13 December 2016

No response

Sterry PRESTA, 2010

Prof. Sterry

Outcomes: PASI 90 & QoL scale

8 and 21 November 2016

No response

Strober 2011

Prof. Strober

Abbvie

Outcome: QoL scale

8 November 2016

Strober sent detailed report for the requested outcomes

Thaci CLEAR, 2015

Prof. Thaçi

Novartis

Outcome: QoL scale

8 and 21 November 2016

Additional data to the publication not provided

Torii 2010

Prof. Torii

Outcomes: PASI 90 & PGA0/1

21 November 2016

Torii sent detailed report for the requested outcomes

Tyring 2006

Prof. Tyring

Outcomes: PGA 0/1 & QoL scale

8 and 21 November 2016

No response

Van Bezooijen 2016

Dr van Bezooijen

Outcomes: PASI 90, adverse effects

4 and 12 January 2017

Additional data to the publication not provided

Van de Kerkhof 2008

Prof. van der Kherkhof Pfizer

Outcome: AEs

8 and 21 November 2016

Additional data to the publication not provided

Yan 2011

No contact

Outcomes: AEs and SAEs

No

Authors' email not found

Zhu LOTUS, 2013

No contact

Outcome: PASI 90

No

Authors' email not found

Awaiting classification studies

Elewski 2016

Prof. Elewski Abbvie

Study's protocol and outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

3 and 12 January 2017

Will be included when published

Khatri 2016

Prof. Khattri

Study's protocol and outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

3 and 12 January 2017

No response

Lee 2016

Prof. Lee

Study's protocol and outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

3 and 12 January 2017

No response

Reich 2016

Prof. Reich

Study's protocol and outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

3 January 2017

Will be included when published

Chow 2015

Prof. Chow

outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

8 November 2016, 16 December 2016

No response

Gurel 2015

Prof. Gurel

Study's protocol and outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

17 and 24 January 2017

Gurel 2015 sent detailed report for the requested outcomes. Finally Gurel study was classified in the included studies section.

Han 2007

No contact

Outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

No

Authors' email not found

NCT01988103

Dr Nogarales, MD Celgene Corporation

Asking for study protocol and efficacy/safety results

12 and 19 January 2017

Email response: "Thank you very much for your email and your interest in our study in Japanese subjects. May I please enquire as to the planned timing for publication for your meta‐analysis as we have just recently submitted our primary manuscript?" Will be included when published

NCT02248792

Prof. Krishna

Asking for study protocol and efficacy/safety results

5 and 12 January 2017

No response

DRKS00000716

Prof. Jacobi

Asking for study protocol and efficacy/safety results

12 and 19 January 2017

No response

CTRI/2015/05/005830

Prof. Shah

Asking for study protocol and efficacy/safety results

12 and 19 January 2017

Abstracts

Yilmaz 2002

Prof. Yilmaz

Outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

16 December 2016

Yilmaz 2002 sent detailed report for the requested outcomes. Finally Yilmaz 2002 study was classified in the included studies section.

Mrowietz 2005

Prof. Mrowietz

Study's protocol and outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

16 December 2016, 3 January 2017

Additional data to the publication not provided. Finally Mrowietz study was classified in the awaiting classification section.

Reich 2004

Prof. Reich

Study's protocol and outcomes: PASI 90, PASI 75, PGA 0/1, QoL scale, AEs & SAEs

16 December 2016

Additional data to the publication not provided. Finally Reich 2004 study was classified in the awaiting classification section.

Ongoing studies

NCT01558310

Dr Yamauchi Dr Patnaik, Director, Clinical Science Institute

Asking for study protocol and efficacy/safety results

5 January 2017

Email response: Dear Dr Sbidian,
Thank you for your kind email, forwarded to me by Dr Paul Yamauchi, MD,PhD. Our " Study to Evaluate the Effectiveness of STELARA ™ (USTEKINUMAB) in the Treatment of Scalp Psoriasis (NCT 01558310)” completed enrolment in December 2016 and the last subject will complete in December 2017, as such we do not have the final data analysis. What is you absolute cut‐ off for publication data ? Would an interim analysis report be acceptable ? Best regards, Rickie Patnaik Director, Clinical Science Institute

Will be included when published

EUCTR2013‐004918‐18‐NL

Prof. Spuls

Asking for study protocol and efficacy/safety results

5 January 2017

Email response "The study is currently ongoing and has not yet been analysed. Therefore, we are not able to provide data on efficacy or safety.
We can provide you with the study protocol. Will this be helpful?
Kind regards, Phyllis Spuls and Celine Busard "

Will be included when published

AE: adverse events; PASI: Psoriasis Area and Severity Index; PGA: Physician Global Assessment; QoL: quality of life; SAE: serious adverse events

Figuras y tablas -
Table 2. Investigators contacted
Table 3. Direct and indirect evidences and network meta‐analysis results summary table for PASI 90 at 12 to 16 weeks

Network meta‐analysis

Direct evidence

Indirect evidence

Comparisons*

RR

LCI

UCI

RR

LCI

UCI

RR

LCI

UCI

FAEs vs placebo

4.09

1.88

8.88

4.47

1.97

10.14

1.86

0.16

21.16

Methotrexate vs placebo

3.91

2.16

7.08

1.53

0.66

3.53

17.16

5.69

51.75

Adalimumab vs placebo

14.87

10.45

21.14

14.42

10.08

20.64

108.8

2.24

5287.86

Etanercept vs placebo

10.79

8.47

13.73

10.62

7.52

15.01

11.21

7.26

17.32

Ustekinumab vs placebo

19.91

15.11

26.23

22.7

15.46

33.34

17.91

12.71

25.24

Secukinumab vs placebo

26.55

20.32

34.69

24.53

14.93

40.32

28.25

19.1

41.78

Ixekizumab vs placebo

32.45

23.61

44.60

39.46

20.64

75.44

24.51

10.05

59.77

Brodalumab vs placebo

25.45

18.74

34.57

26.58

16.65

42.41

23.74

10.09

55.86

Apremilast vs placebo

7.66

4.30

13.66

6.72

3.07

14.69

10.83

2.43

48.31

Tofacitinib vs placebo

8.50

6.23

11.60

6.3

4.14

9.56

17.91

8.3

38.62

Guselkumab vs placebo

21.03

14.56

30.38

26.1

14.71

46.3

12.7

4.28

37.69

Methotrexate vs FAEs

0.96

0.38

2.44

2

0.19

21.03

0.83

0.3

2.32

Alefacept vs methotrexate

1.12

0.42

3.02

1.12

0.42

3.02

Ciclosporin vs methotrexate

1.02

0.60

1.73

1.02

0.6

1.73

Infliximab vs methotrexate

2.86

2.06

3.97

2.86

2.06

3.97

Adalimumab vs methotrexate

3.80

2.26

6.39

3.35

2.02

5.57

13.2

3.4

51.32

Etanercept vs acitretin

11.00

0.63

191.47

11

0.63

191.47

Guselkumab vs adalimumab

1.41

1.21

1.65

1.4

1.18

1.66

2.88

0.68

12.21

Ustekinumab vs etanercept

1.85

1.50

2.27

1.8

1.27

2.55

1.95

1.37

2.77

Secukinumab vs etanercept

2.46

2.01

3.02

2.33

1.66

3.28

2.62

1.82

3.77

Ixekizumab vs etanercept

3.01

2.46

3.68

2.93

2.44

3.53

5.73

2.07

15.85

Apremilast vs etanercept

0.71

0.40

1.25

0.72

0.36

1.45

0.69

0.26

1.81

Tofacitinib vs etanercept

0.79

0.59

1.06

0.88

0.73

1.08

0.49

0.3

0.81

Secukinumab vs ustekinumab

1.33

1.11

1.61

1.38

1.03

1.84

1.19

0.79

1.81

Brodalumab vs ustekinumab

1.28

1.10

1.48

1.27

1.1

1.46

1.64

0.69

3.89

FAES: fumaric acid esters; LCI: low confidence interval; RR: risk ratio; UCI: upper confidence interval; vs: versus,

*The comparisons listed in this table were included in at least one direct‐evidence analysis.

Figuras y tablas -
Table 3. Direct and indirect evidences and network meta‐analysis results summary table for PASI 90 at 12 to 16 weeks
Table 4. Ranking findings for all outcomes at class level

Class‐level
interventions

SUCRA
PASI 90

Rank
PASI 90

SUCRA
SAE

Rank
SAE

SUCRA
PASI 75

Rank
PASI 75

SUCRA
AE

Rank
AE

SUCRA
PGA

Rank
PGA

SUCRA
QoL

Rank
QoL

Anti‐IL12/23

85.7

2

53.9

3

85.0

2

57.0

3

83.8

2

75.7

3

Anti‐IL17

100.0

1

21.0

8

99.6

1

14.1

6

99.9

1

95.4

1

Anti‐IL23

71.3

3

39.6

5

72.2

3

78.7

2

73.1

3

83.4

2

Anti‐TNF alpha

56.4

4

39.2

6

57.4

4

47.5

5

57.5

4

58.4

4

Other biologics

26.3

6

68.2

2

17.0

7

_

_

16.6

7

15.5

7

Small molecules

41.5

5

45.4

4

42.7

5

7.9

7

42.0

5

40.4

5

Conventional systemic

treatments

18.7

7

94.8

1

26.0

6

50.8

4

27.1

6

30.8

6

Placebo

0

8

38.0

7

0

8

94.0

1

0

8

0.4

8

AE: adverse events; FAEs: fumaric acid esters; PGA: Physician Global Assessment; QoL: Specific quality of life scale; SAE: serious adverse events

Figuras y tablas -
Table 4. Ranking findings for all outcomes at class level
Table 5. Ranking findings for all outcomes at drug level

Drug

SUCRA
PASI 90

Rank
PASI 90

SUCRA
SAE

Rank
SAE

SUCRA
PASI 75

Rank
PASI 75

SUCRA
AE

Rank
AE

SUCRA
PGA

Rank
PGA

SUCRA
QoL

Rank
QoL

Acitretin

9.9

19

46.9

9

26.0

15

Adalimumab

63.1

8

40.4

14

60.2

9

70.1

5

56.9

8

57.6

7

Alefacept

25.3

15

62.6

5

12.6

18

13.1

18

15.9

13

Apremilast

39.7

13

54.7

7

33.2

14

14.3

16

27.9

14

28.6

10

Brodalumab

84.3

3

39.8

15

82.1

3

46.4

9

84.0

5

52.3

8

Certolizumab

75.7

5

70.9

3

71.6

6

78.0

4

90.1

1

Ciclosporin

21.3

17

78.2

2

33.2

13

36.8

12

24.0

16

Etanercept

52.6

11

43.6

11

57.7

10

45.9

10

51.7

10

67.6

5

FAEs

21.9

16

57.7

6

11.1

19

17.8

15

15.4

17

Guselkumab

77.0

4

42.6

12

71.6

7

78.2

3

67.5

7

84.3

2

Infliximab

53.2

10

64.4

4

48.0

11

40.1

11

52.4

9

Itolizumab

56.0

9

71.6

8

29.4

13

16.0

12

Ixekizumab

94.3

1

33.7

17

91.8

1

18.1

14

85.9

3

99.2

1

Methotrexate

20.2

18

90.7

1

21.3

16

68.4

6

24.9

15

31.5

9

Placebo

2.9

20

42.0

13

0.0

20

88.0

1

0.3

19

1.2

14

Ponesimod

37.3

14

18.1

19

21.3

17

14.0

17

48.7

11

28.1

11

Secukinumab

86.5

2

29.9

18

86.7

2

36.3

13

84.4

4

Tildrakizumab

63.6

7

37.8

16

78.3

4

86.1

2

86.3

2

74.9

4

Tofacitinib

42.5

12

44.0

10

46.2

12

47.3

8

36.6

12

65.1

6

Ustekinumab

72.6

6

52.0

8

75.2

5

64.3

7

70.4

6

77.4

3

AE: adverse events; FAEs: fumaric acid esters; PASI: Psoriasis Area and Severity Index; PGA: Physician Global Assessment; QoL: specific quality of life scale; SAE: serious adverse events; SUCRA: Surface Under the Cumulative Ranking

Figuras y tablas -
Table 5. Ranking findings for all outcomes at drug level
Table 6. Total number of serious adverse events during the induction phase at class‐level and most severe types

Number of randomised participants

Number of serious adverse events

Number of serious infections

Number of malignancies

Number of MACE

Drug

Placebo

Drug

Placebo

Drug

Placebo

Drug

Placebo

Drug

Placebo

Conventional systemic agents

767

220

19

10

0

0

0

0

0

0

Anti‐TNF

4508

2640

85

44

21

9

20

7

6

2

Anti‐IL12/23

2547

1607

38

23

7

5

4

1

4

3

Anti‐IL17

7551

2533

149

36

47

7

21

2

19

3

Anti‐IL23

1347

510

23

7

4

1

0

0

1

0

Other biologics

509

227

15

10

2

1

Small molecules

3920

1280

89

28

15

5

14

0

5

1

MACE: Major adverse cardiac events

Figuras y tablas -
Table 6. Total number of serious adverse events during the induction phase at class‐level and most severe types
Table 7. Direct and indirect evidence and network meta‐analysis results summary table for serious adverse events at 12 to 16 weeks

Network meta‐analysis

Direct evidence

Indirect evidence

Comparisons*

RR

LCI

UCI

RR

LCI

UCI

RR

LCI

UCI

FAEs vs placebo

0.77

0.30

1.99

0.83

0.31

2.21

0.19

0

12.57

Methotrexate vs placebo

0.23

0.05

0.99

0.16

0.03

0.86

0.68

0.04

11.67

Adalimumab vs placebo

1.02

0.61

1.73

1.05

0.62

1.78

0.07

0

26.92

Etanercept vs placebo

0.99

0.65

1.51

1.09

0.65

1.84

0.76

0.31

1.89

Ustekinumab vs placebo

0.89

0.57

1.39

0.74

0.44

1.26

1.36

0.61

2.99

Secukinumab vs placebo

1.19

0.69

2.03

1.61

0.78

3.33

0.75

0.3

1.87

Ixekizumab vs placebo

1.12

0.66

1.90

1.16

0.62

2.16

0.97

0.18

5.12

Brodalumab vs placebo

1.04

0.62

1.73

0.92

0.53

1.62

2.77

0.38

20.28

Apremilast vs placebo

0.84

0.47

1.52

0.78

0.42

1.44

4.33

0.09

201.27

Tofacitinib vs placebo

0.98

0.55

1.76

1.05

0.53

2.06

0.67

0.08

5.35

Guselkumab vs placebo

1.00

0.49

2.04

1.21

0.51

2.85

0.52

0.08

3.41

Methotrexate vs FAEs

0.30

0.06

1.59

1

0.02

48.83

0.23

0.04

1.45

Ciclosporin vs methotrexate

0.98

0.06

15.38

0.98

0.06

15.38

Infliximab vs methotrexate

2.41

1.04

5.59

2.41

1.04

5.59

Adalimumab vs methotrexate

4.43

0.99

19.81

2.24

0.21

23.56

6.68

1.04

42.76

Etanercept vs acitretin

1.00

0.02

48.82

1

0.02

48.83

Guselkumab vs adalimumab

0.98

0.51

1.88

0.89

0.44

1.79

2.07

0.26

16.45

Ustekinumab vs etanercept

0.90

0.52

1.57

1.25

0.38

4.11

0.83

0.44

1.54

Secukinumab vs etanercept

1.20

0.66

2.19

1.17

0.45

3.04

1.22

0.56

2.65

Ixekizumab vs etanercept

1.14

0.66

1.94

1.02

0.53

1.95

1.47

0.53

4.09

Apremilast vs etanercept

0.85

0.42

1.72

2.69

0.41

17.5

0.7

0.33

1.5

Tofacitinib vs etanercept

0.99

0.53

1.87

0.87

0.35

2.19

1.12

0.47

2.7

Secukinumab vs ustekinumab

1.33

0.74

2.38

1.01

0.42

2.39

1.68

0.77

3.68

Brodalumab vs ustekinumab

1.16

0.64

2.11

1.32

0.59

2.98

0.95

0.33

2.71

FAES: fumaric acid esters; LCI: low confidence interval; RR: risk ratio; UCI: upper confidence interval

*The comparisons listed in this table were included in at least one direct‐evidence analysis.

Figuras y tablas -
Table 7. Direct and indirect evidence and network meta‐analysis results summary table for serious adverse events at 12 to 16 weeks
Comparison 1. Primary outcome ‐ PASI 90

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Conventional systemic agents versus placebo Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Methotrexate

2

282

Risk Ratio (M‐H, Random, 95% CI)

2.60 [0.26, 25.90]

1.2 Fumaric acid esters

1

704

Risk Ratio (M‐H, Random, 95% CI)

4.47 [2.01, 9.95]

2 Conventional systemic 1 versus conventional systemic 2 Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Ciclosporin versus methotrexate

2

172

Risk Ratio (M‐H, Random, 95% CI)

1.18 [0.47, 2.98]

2.2 Methotrexate versus fumaric acid esters

1

60

Risk Ratio (M‐H, Random, 95% CI)

2.0 [0.19, 20.90]

3 Anti‐TNF alpha versus placebo Show forest plot

21

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

3.1 Etanercept versus placebo

12

4954

Risk Ratio (M‐H, Random, 95% CI)

11.17 [7.66, 16.28]

3.2 Adalimumab versus placebo

8

3199

Risk Ratio (M‐H, Random, 95% CI)

14.86 [8.93, 24.73]

3.3 Certolizumab versus placebo

1

176

Risk Ratio (M‐H, Random, 95% CI)

24.58 [3.48, 173.49]

4 Ustekinumab versus placebo Show forest plot

7

3832

Risk Ratio (M‐H, Random, 95% CI)

22.59 [14.74, 34.64]

5 Anti‐IL17 versus placebo Show forest plot

16

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Secukinumab versus placebo

7

2707

Risk Ratio (M‐H, Random, 95% CI)

26.52 [14.91, 47.17]

5.2 Ixekizumab versus placebo

4

3268

Risk Ratio (M‐H, Random, 95% CI)

53.85 [15.34, 189.07]

5.3 Brodalumab versus placebo

5

4109

Risk Ratio (M‐H, Random, 95% CI)

26.33 [16.77, 41.33]

6 Anti‐IL23 versus placebo Show forest plot

4

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6.1 Guselkumab versus placebo

3

1502

Risk Ratio (M‐H, Random, 95% CI)

24.87 [14.20, 43.55]

6.2 Tildrakizumab versus placebo

1

355

Risk Ratio (M‐H, Random, 95% CI)

15.63 [2.24, 109.29]

7 Other biologics Show forest plot

1

225

Risk Ratio (M‐H, Random, 95% CI)

12.26 [0.76, 197.54]

7.1 Itolizumab versus placebo

1

225

Risk Ratio (M‐H, Random, 95% CI)

12.26 [0.76, 197.54]

8 Biologic versus conventional systemic treatments Show forest plot

4

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

8.1 Etanercept versus acitretin

1

60

Risk Ratio (M‐H, Random, 95% CI)

11.00 [0.64, 190.53]

8.2 Infliximab versus methotrexate

1

868

Risk Ratio (M‐H, Random, 95% CI)

2.86 [2.15, 3.80]

8.3 Adalimumab versus methotrexate

1

218

Risk Ratio (M‐H, Random, 95% CI)

3.73 [2.25, 6.19]

8.4 Alefacept versus methotrexate

1

212

Risk Ratio (M‐H, Random, 95% CI)

1.12 [0.42, 2.98]

9 Biologic 1 versus biologic 2 Show forest plot

10

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

9.1 Ustekinumab versus Etanercept

1

903

Risk Ratio (M‐H, Random, 95% CI)

1.80 [1.45, 2.24]

9.2 Secukinumab versus etanercept

1

980

Risk Ratio (M‐H, Random, 95% CI)

2.32 [1.85, 2.92]

9.3 Ixekizumab versus etanercept

2

2209

Risk Ratio (M‐H, Random, 95% CI)

2.98 [2.24, 3.98]

9.4 Secukinumab versus ustekinumab

1

676

Risk Ratio (M‐H, Random, 95% CI)

1.38 [1.23, 1.53]

9.5 Brodalumab versus ustekinumab

2

3088

Risk Ratio (M‐H, Random, 95% CI)

1.27 [1.16, 1.39]

9.6 Guselkumab versus adalimumab

3

1658

Risk Ratio (M‐H, Random, 95% CI)

1.41 [1.25, 1.60]

10 Small molecules versus placebo Show forest plot

9

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

10.1 Apremilast versus placebo

4

1775

Risk Ratio (M‐H, Random, 95% CI)

6.78 [3.03, 15.17]

10.2 Tofacitinib versus placebo

4

2826

Risk Ratio (M‐H, Random, 95% CI)

6.80 [3.86, 11.99]

10.3 Ponesimod versus placebo

1

326

Risk Ratio (M‐H, Random, 95% CI)

6.60 [1.65, 26.41]

11 Biologic versus small molecules Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

11.1 Etanercept versus Tofacitinib

1

998

Risk Ratio (M‐H, Random, 95% CI)

1.13 [0.93, 1.38]

11.2 Etanercept versus apremilast

1

166

Risk Ratio (M‐H, Random, 95% CI)

1.42 [0.72, 2.78]

Figuras y tablas -
Comparison 1. Primary outcome ‐ PASI 90
Comparison 2. Primary outcome ‐ serious adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Conventional systemic agents versus placebo Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Methotrexate

2

283

Risk Ratio (M‐H, Random, 95% CI)

0.16 [0.03, 0.88]

1.2 Fumaric acid esters

1

704

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.31, 2.21]

2 Anti‐TNF alpha versus placebo Show forest plot

20

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Etanercept versus placebo

11

3783

Risk Ratio (M‐H, Random, 95% CI)

1.06 [0.61, 1.83]

2.2 Adalimumab versus placebo

8

3199

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.60, 1.73]

2.3 Certolizumab versus placebo

1

176

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.10, 2.36]

3 Ustekinumab versus placebo Show forest plot

8

4154

Risk Ratio (M‐H, Random, 95% CI)

0.89 [0.50, 1.58]

4 Anti‐IL17 versus placebo Show forest plot

16

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4.1 Secukinumab versus placebo

7

2707

Risk Ratio (M‐H, Random, 95% CI)

1.67 [0.79, 3.53]

4.2 Ixekizumab versus placebo

4

3268

Risk Ratio (M‐H, Random, 95% CI)

1.23 [0.65, 2.32]

4.3 Brodalumab versus placebo

5

4109

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.52, 1.61]

5 Anti‐IL23 versus placebo Show forest plot

4

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Guselkumab versus placebo

3

1502

Risk Ratio (M‐H, Random, 95% CI)

1.21 [0.51, 2.85]

5.2 Tildrakizumab versus placebo

1

355

Risk Ratio (M‐H, Random, 95% CI)

1.36 [0.07, 24.94]

6 Other biologics Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6.1 Alefacept versus placebo

2

736

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.34, 1.62]

7 Biologic versus conventional systemic treatments Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

7.1 Etanercept versus acitretin

1

60

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Infliximab versus methotrexate

1

868

Risk Ratio (M‐H, Random, 95% CI)

2.41 [1.04, 5.59]

7.3 Adalimumab versus methotrexate

1

218

Risk Ratio (M‐H, Random, 95% CI)

2.04 [0.19, 22.14]

8 Biologic 1 versus biologic 2 Show forest plot

10

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

8.1 Ustekinumab versus etanercept

1

903

Risk Ratio (M‐H, Random, 95% CI)

1.25 [0.38, 4.11]

8.2 Secukinumab versus etanercept

1

980

Risk Ratio (M‐H, Random, 95% CI)

1.08 [0.41, 2.82]

8.3 Ixekizumab versus etanercept

2

2209

Risk Ratio (M‐H, Random, 95% CI)

1.07 [0.55, 2.06]

8.4 Secukinumab versus ustekinumab

1

676

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.42, 2.39]

8.5 Brodalumab versus ustekinumab

2

3088

Risk Ratio (M‐H, Random, 95% CI)

1.51 [0.64, 3.56]

8.6 Guselkumab versus adalimumab

3

1658

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.44, 1.82]

9 Small molecules versus placebo Show forest plot

11

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

9.1 Apremilast versus placebo

5

2036

Risk Ratio (M‐H, Random, 95% CI)

0.79 [0.41, 1.49]

9.2 Tofacitinib versus placebo

5

2838

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.53, 2.06]

9.3 Ponesimod versus placebo

1

326

Risk Ratio (M‐H, Random, 95% CI)

2.59 [0.34, 19.85]

10 Biologic versus small molecules Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

10.1 Etanercept versus tofacitinib

1

998

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.46, 2.89]

10.2 Etanercept versus apremilast

1

166

Risk Ratio (M‐H, Random, 95% CI)

0.33 [0.04, 3.14]

Figuras y tablas -
Comparison 2. Primary outcome ‐ serious adverse events
Comparison 3. Secondary outcome ‐ PASI 75

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Conventional systemic agents versus placebo Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Methotrexate

2

283

Risk Ratio (M‐H, Random, 95% CI)

2.36 [1.19, 4.68]

1.2 Fumaric acid esters

1

704

Risk Ratio (M‐H, Random, 95% CI)

2.56 [1.68, 3.89]

2 Conventional systemic 1 versus conventional systemic 2 Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Ciclosporin versus methotrexate

2

172

Risk Ratio (M‐H, Random, 95% CI)

1.37 [0.84, 2.23]

2.2 Methotrexate versus fumaric acid esters

1

60

Risk Ratio (M‐H, Random, 95% CI)

1.2 [0.41, 3.51]

3 Anti‐TNF alpha versus placebo Show forest plot

22

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

3.1 Etanercept versus placebo

13

5066

Risk Ratio (M‐H, Random, 95% CI)

8.55 [6.94, 10.52]

3.2 Adalimumab versus placebo

8

3199

Risk Ratio (M‐H, Random, 95% CI)

9.08 [6.52, 12.65]

3.3 Certolizumab versus placebo

1

176

Risk Ratio (M‐H, Random, 95% CI)

11.31 [4.37, 29.24]

4 Ustekinumab versus placebo Show forest plot

8

4154

Risk Ratio (M‐H, Random, 95% CI)

12.41 [8.69, 17.71]

5 Anti‐IL17 versus placebo Show forest plot

16

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Secukinumab versus placebo

7

2707

Risk Ratio (M‐H, Random, 95% CI)

15.70 [11.27, 21.87]

5.2 Ixekizumab versus placebo

4

3268

Risk Ratio (M‐H, Random, 95% CI)

17.44 [10.45, 29.10]

5.3 Brodalumab versus placebo

5

4109

Risk Ratio (M‐H, Random, 95% CI)

12.80 [8.46, 19.36]

6 Anti‐IL23 versus placebo Show forest plot

4

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6.1 Guselkumab versus Placebo

3

1502

Risk Ratio (M‐H, Random, 95% CI)

12.28 [8.79, 17.17]

6.2 Tildrakizumab versus placebo

1

355

Risk Ratio (M‐H, Random, 95% CI)

14.51 [3.73, 56.45]

7 Other biologics Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

7.1 Alefacept versus placebo

2

736

Risk Ratio (M‐H, Random, 95% CI)

2.95 [1.76, 4.94]

7.2 Itolizumab versus placebo

1

225

Risk Ratio (M‐H, Random, 95% CI)

13.23 [1.88, 92.93]

8 Biologic versus conventional systemic treatments Show forest plot

4

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

8.1 Etanercept versus acitretin

1

60

Risk Ratio (M‐H, Random, 95% CI)

2.13 [1.09, 4.16]

8.2 Alefacept versus methotrexate

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.46, 1.21]

8.3 Infliximab versus methotrexate

1

868

Risk Ratio (M‐H, Random, 95% CI)

1.86 [1.58, 2.19]

8.4 Adalimumab versus methotrexate

1

218

Risk Ratio (M‐H, Random, 95% CI)

2.25 [1.72, 2.94]

9 Biologic 1 versus biologic 2 Show forest plot

10

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

9.1 Ustekinumab versus etanercept

1

903

Risk Ratio (M‐H, Random, 95% CI)

1.26 [1.13, 1.40]

9.2 Secukinumab versus etanercept

1

980

Risk Ratio (M‐H, Random, 95% CI)

1.64 [1.44, 1.88]

9.3 Ixekizumab versus etanercept

2

2209

Risk Ratio (M‐H, Random, 95% CI)

1.79 [1.43, 2.24]

9.4 Secukinumab versus ustekinumab

1

676

Risk Ratio (M‐H, Random, 95% CI)

1.13 [1.06, 1.20]

9.5 Brodalumab versus ustekinumab

2

3088

Risk Ratio (M‐H, Random, 95% CI)

1.10 [1.04, 1.17]

9.6 Guselkumab versus adalimumab

3

1658

Risk Ratio (M‐H, Random, 95% CI)

1.21 [1.13, 1.30]

10 Small molecules versus placebo Show forest plot

11

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

10.1 Apremilast versus placebo

5

2036

Risk Ratio (M‐H, Random, 95% CI)

3.88 [2.42, 6.22]

10.2 Tofacitinib versus placebo

5

2838

Risk Ratio (M‐H, Random, 95% CI)

6.41 [3.84, 10.71]

10.3 Ponesimod versus placebo

1

326

Risk Ratio (M‐H, Random, 95% CI)

3.51 [1.88, 6.53]

11 Biologic versus small molecules Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

11.1 Etanercept versus Tofacitinib

1

998

Risk Ratio (M‐H, Random, 95% CI)

1.14 [1.02, 1.28]

11.2 Etanercept versus apremilast

1

166

Risk Ratio (M‐H, Random, 95% CI)

1.21 [0.86, 1.71]

Figuras y tablas -
Comparison 3. Secondary outcome ‐ PASI 75
Comparison 4. Secondary outcome ‐ PGA 0/1

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Conventional systemic agents versus placebo Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Methotrexate

2

283

Risk Ratio (M‐H, Random, 95% CI)

2.94 [1.47, 5.89]

1.2 Fumaric acid esters

1

704

Risk Ratio (M‐H, Random, 95% CI)

2.73 [1.72, 4.32]

2 Conventional systemic 1 versus conventional systemic 2 Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Ciclosporin versus methotrexate

1

88

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.47, 1.46]

3 Anti‐TNF alpha versus placebo Show forest plot

19

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

3.1 Etanercept versus placebo

11

4334

Risk Ratio (M‐H, Random, 95% CI)

7.77 [5.98, 10.10]

3.2 Adalimumab versus placebo

7

3051

Risk Ratio (M‐H, Random, 95% CI)

8.38 [6.28, 11.18]

3.3 Certolizumab versus placebo

1

176

Risk Ratio (M‐H, Random, 95% CI)

35.88 [5.11, 251.73]

4 Ustekinumab versus placebo Show forest plot

8

4154

Risk Ratio (M‐H, Random, 95% CI)

11.33 [7.38, 17.39]

5 Anti‐IL17 versus placebo Show forest plot

15

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Secukinumab versus placebo

6

2607

Risk Ratio (M‐H, Random, 95% CI)

17.16 [7.48, 39.36]

5.2 Ixekizumab versus placebo

4

3268

Risk Ratio (M‐H, Random, 95% CI)

17.46 [9.87, 30.90]

5.3 Brodalumab versus placebo

5

4109

Risk Ratio (M‐H, Random, 95% CI)

18.78 [13.29, 26.55]

6 Anti‐IL23 versus placebo Show forest plot

4

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6.1 Guselkumab versus placebo

3

1502

Risk Ratio (M‐H, Random, 95% CI)

10.59 [7.73, 14.51]

6.2 Tildrakizumab versus placebo

1

355

Risk Ratio (M‐H, Random, 95% CI)

27.54 [3.95, 191.78]

7 Other biologics Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

7.1 Alefacept versus placebo

1

507

Risk Ratio (M‐H, Random, 95% CI)

2.54 [1.22, 5.29]

7.2 Itolizumab versus placebo

1

225

Risk Ratio (M‐H, Random, 95% CI)

3.78 [0.94, 15.17]

8 Biologic versus conventional systemic treatments Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

8.1 Alefacept versus methotrexate

1

212

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.37, 1.29]

8.2 Infliximab versus methotrexate

1

868

Risk Ratio (M‐H, Random, 95% CI)

1.99 [1.67, 2.37]

8.3 Adalimumab versus methotrexate

1

218

Risk Ratio (M‐H, Random, 95% CI)

2.44 [1.79, 3.32]

9 Biologic 1 versus biologic 2 Show forest plot

10

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

9.1 Ustekinumab versus etanercept

1

903

Risk Ratio (M‐H, Random, 95% CI)

1.40 [1.24, 1.58]

9.2 Secukinumab versus etanercept

1

980

Risk Ratio (M‐H, Random, 95% CI)

2.09 [1.73, 2.53]

9.3 Ixekizumab versus etanercept

2

2209

Risk Ratio (M‐H, Random, 95% CI)

2.01 [1.74, 2.31]

9.4 Secukinumab versus ustekinumab

1

676

Risk Ratio (M‐H, Random, 95% CI)

1.23 [1.13, 1.35]

9.5 Brodalumab versus ustekinumab

2

3088

Risk Ratio (M‐H, Random, 95% CI)

1.17 [1.07, 1.27]

9.6 Guselkumab versus adalimumab

3

1658

Risk Ratio (M‐H, Random, 95% CI)

1.24 [1.17, 1.32]

10 Small molecules versus placebo Show forest plot

10

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

10.1 Apremilast versus placebo

4

1776

Risk Ratio (M‐H, Random, 95% CI)

3.88 [2.04, 7.38]

10.2 Tofacitinib versus placebo

5

2838

Risk Ratio (M‐H, Random, 95% CI)

4.48 [3.51, 5.71]

10.3 Ponesimod versus placebo

1

326

Risk Ratio (M‐H, Random, 95% CI)

6.73 [2.19, 20.64]

11 Biologic versus small molecules Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

11.1 Etanercept versus tofacitinib

1

998

Risk Ratio (M‐H, Random, 95% CI)

1.15 [1.04, 1.27]

11.2 Etanercept versus apremilast

1

166

Risk Ratio (M‐H, Random, 95% CI)

1.33 [0.78, 2.27]

Figuras y tablas -
Comparison 4. Secondary outcome ‐ PGA 0/1
Comparison 5. Secondary outcome ‐ quality of life

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Conventional systemic agents versus placebo Show forest plot

2

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

1.1 Methotrexate

2

283

Std. Mean Difference (IV, Random, 95% CI)

‐0.67 [‐1.40, 0.06]

2 Anti‐TNF alpha versus placebo Show forest plot

14

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

2.1 Etanercept versus placebo

7

2779

Std. Mean Difference (IV, Random, 95% CI)

‐1.10 [‐1.37, ‐0.83]

2.2 Adalimumab versus placebo

7

2774

Std. Mean Difference (IV, Random, 95% CI)

‐1.02 [‐1.16, ‐0.88]

3 Ustekinumab versus placebo Show forest plot

6

2917

Std. Mean Difference (IV, Random, 95% CI)

‐1.21 [‐1.39, ‐1.03]

4 Anti‐IL17 versus placebo Show forest plot

5

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

4.1 Ixekizumab versus placebo

3

3126

Std. Mean Difference (IV, Random, 95% CI)

‐1.76 [‐2.09, ‐1.43]

4.2 Brodalumab versus placebo

2

349

Std. Mean Difference (IV, Random, 95% CI)

‐0.96 [‐1.44, ‐0.47]

5 Anti‐IL23 versus placebo Show forest plot

3

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

5.1 Guselkumab versus placebo

2

1252

Std. Mean Difference (IV, Random, 95% CI)

‐1.39 [‐1.63, ‐1.14]

5.2 Tildrakizumab versus placebo

1

355

Std. Mean Difference (IV, Random, 95% CI)

‐1.23 [‐1.55, ‐0.91]

6 Other biologics Show forest plot

2

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

6.1 Alefacept versus placebo

1

229

Std. Mean Difference (IV, Random, 95% CI)

‐0.32 [‐0.62, ‐0.02]

6.2 Itolizumab versus placebo

1

225

Std. Mean Difference (IV, Random, 95% CI)

‐0.34 [‐0.68, ‐0.01]

7 Biologic versus conventional systemic treatments Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

7.1 Alefacept versus methotrexate

1

212

Mean Difference (IV, Fixed, 95% CI)

1.31 [‐0.28, 2.90]

7.2 Adalimumab versus methotrexate

1

218

Mean Difference (IV, Fixed, 95% CI)

‐3.40 [‐5.75, ‐1.05]

8 Biologic 1 versus biologic 2 Show forest plot

4

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

8.1 Ixekizumab versus etanercept

2

2209

Mean Difference (IV, Fixed, 95% CI)

‐1.99 [‐2.39, ‐1.59]

8.2 Guselkumab versus adalimumab

2

1407

Mean Difference (IV, Fixed, 95% CI)

‐1.73 [‐2.50, ‐0.97]

9 Small molecules versus placebo Show forest plot

7

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

9.1 Apremilast versus placebo

3

1609

Std. Mean Difference (IV, Random, 95% CI)

‐0.62 [‐0.77, ‐0.47]

9.2 Tofacitinib versus placebo

3

2629

Std. Mean Difference (IV, Random, 95% CI)

‐1.09 [‐1.28, ‐0.89]

9.3 Ponesimod versus placebo

1

326

Std. Mean Difference (IV, Random, 95% CI)

‐0.58 [‐0.86, ‐0.31]

10 Biologic versus small molecules Show forest plot

1

Std. Mean Difference (IV, Random, 95% CI)

Subtotals only

10.1 Etanercept versus Tofacitinib

1

998

Std. Mean Difference (IV, Random, 95% CI)

‐0.06 [‐0.19, 0.07]

Figuras y tablas -
Comparison 5. Secondary outcome ‐ quality of life
Comparison 6. Secondary outcome ‐ adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Conventional systemic agents versus placebo Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Methotrexate

2

283

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.81, 1.10]

1.2 Fumaric acid esters

1

704

Risk Ratio (M‐H, Random, 95% CI)

1.40 [1.22, 1.62]

2 Conventional systemic 1 versus conventional systemic 2 Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Ciclosporin versus methotrexate

2

172

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.90, 1.34]

2.2 Methotrexate versus fumaric acid esters

1

60

Risk Ratio (M‐H, Random, 95% CI)

1.13 [0.91, 1.39]

3 Anti‐TNF alpha versus placebo Show forest plot

17

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

3.1 Etanercept versus placebo

9

3529

Risk Ratio (M‐H, Random, 95% CI)

1.12 [1.05, 1.20]

3.2 Adalimumab versus placebo

7

3051

Risk Ratio (M‐H, Random, 95% CI)

1.06 [1.00, 1.13]

3.3 Certolizumab versus placebo

1

176

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.81, 1.22]

4 Ustekinumab versus placebo Show forest plot

8

4154

Risk Ratio (M‐H, Random, 95% CI)

1.06 [1.00, 1.13]

5 Anti‐IL17 versus placebo Show forest plot

16

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Secukinumab versus placebo

7

2707

Risk Ratio (M‐H, Random, 95% CI)

1.15 [1.02, 1.29]

5.2 Ixekizumab versus placebo

4

3268

Risk Ratio (M‐H, Random, 95% CI)

1.24 [1.07, 1.45]

5.3 Brodalumab versus placebo

5

4109

Risk Ratio (M‐H, Random, 95% CI)

1.15 [1.00, 1.32]

6 Anti‐IL23 versus placebo Show forest plot

4

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

6.1 Guselkumab versus placebo

3

1502

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.92, 1.16]

6.2 Tildrakizumab versus placebo

1

355

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.76, 1.18]

7 Biologic versus conventional systemic treatments Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

7.1 Infliximab versus methotrexate

1

868

Risk Ratio (M‐H, Random, 95% CI)

1.08 [0.97, 1.20]

7.2 Adalimumab versus methotrexate

1

218

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.78, 1.05]

8 Biologic 1 versus biologic 2 Show forest plot

10

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

8.1 Ustekinumab versus etanercept

1

903

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.89, 1.06]

8.2 Secukinumab versus etanercept

1

980

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.89, 1.12]

8.3 Ixekizumab versus etanercept

2

2209

Risk Ratio (M‐H, Random, 95% CI)

1.06 [0.97, 1.15]

8.4 Secukinumab versus ustekinumab

1

676

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.98, 1.25]

8.5 Brodalumab versus ustekinumab

2

3088

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.93, 1.09]

8.6 Guselkumab versus adalimumab

3

1658

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.88, 1.07]

9 Small molecules versus placebo Show forest plot

10

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

9.1 Apremilast versus placebo

5

2036

Risk Ratio (M‐H, Random, 95% CI)

1.22 [1.07, 1.38]

9.2 Tofacitinib versus placebo

4

2641

Risk Ratio (M‐H, Random, 95% CI)

1.14 [1.03, 1.25]

9.3 Ponesimod versus placebo

1

326

Risk Ratio (M‐H, Random, 95% CI)

1.31 [1.02, 1.68]

10 Biologic versus small molecules Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

10.1 Etanercept versus tofacitinib

1

998

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.89, 1.12]

10.2 Etanercept versus apremilast

1

166

Risk Ratio (M‐H, Random, 95% CI)

1.32 [1.03, 1.69]

Figuras y tablas -
Comparison 6. Secondary outcome ‐ adverse events