Adalimumab 40 mg every other week compared to placebo for fatigue in inflammatory bowel disease

Patient or population: participants with moderately‐to‐severely active disease
Setting: 92 centres in the United States, Europe, Canada, Australia and South Africa
Intervention: adalimumab 40 mg every other week
Comparison: placebo

Outcomes

Anticipated absolute effects^* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo

Risk with adalimumab 40 mg every other week

Fatigue
assessed with: FACIT‐Fatigue
follow‐up: 56 weeks

The mean fatigue score was 32.5

MD 4.3 higher
(1.75 higher to 6.85 higher)

‐

337
(1 RCT)

⊕⊕⊝⊝
LOW ¹

FACIT‐F scores ranged from 0 to 52, with higher scores indicating less fatigue.

Fatigue
assessed with: SF‐36 Vitality
follow‐up: 56 weeks

The mean fatigue score was 54.8

MD 2.8 higher
(5.1 lower to 10.7 higher)

‐

143
(1 RCT)

⊕⊕⊝⊝
LOW ²

SF‐36 vitality subscale scores ranged from 0 to 100, with higher scores indicating greater vitality (less fatigue).

Quality of life
assessed with: IBDQ
follow‐up: 56 weeks

The mean quality of life score was 172.9

MD 10.4 higher
(0.53 lower to 21.33 higher)

‐

145
(1 RCT)

⊕⊕⊝⊝
LOW ²

IBDQ scores ranged from 32 to 224, with higher scores indicating better quality of life.

Adverse events
assessed with: MedDRA
follow‐up: 56 weeks

847 per 1,000

888 per 1,000
(826 to 930)

OR 1.44
(0.86 to 2.41)

521
(1 RCT)

⊕⊕⊕⊝
MODERATE ³

Serious adverse events
assessed with: MedDRA
follow‐up: 56 weeks

153 per 1,000

92 per 1,000
(56 to 148)

OR 0.56
(0.33 to 0.96)

521
(1 RCT)

⊕⊕⊕⊝
MODERATE ³

Withdrawal due to adverse events
assessed with: MedDRA
follow‐up: 56 weeks

134 per 1,000

69 per 1,000
(39 to 119)

OR 0.48
(0.26 to 0.87)

521
(1 RCT)

⊕⊕⊕⊝
MODERATE ³

*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; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: 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: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Adalimumab 40 mg weekly compared to placebo for fatigue in inflammatory bowel disease

Patient or population: fatigue in inflammatory bowel disease
Setting: 92 centres in the United States, Europe, Canada, Australia and South Africa
Intervention: adalimumab 40 mg weekly
Comparison: placebo

Outcomes

Anticipated absolute effects^* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo

Risk with adalimumab 40 mg weekly

Fatigue
assessed with: FACIT‐Fatigue
follow‐up: 56 weeks

The mean fatigue score was 32.5

MD 2.5 higher
(0.26 lower to 5.26 higher)

‐

327
(1 RCT)

⊕⊕⊝⊝
LOW ¹

FACIT‐F scores ranged from 0 to 52 with higher scores indicating less fatigue.

Fatigue
assessed with: SF‐36 vitality
follow‐up: 56 weeks

The mean fatigue score was 54.8

MD 3.2 higher
(4.72 lower to 11.13 higher)

‐

145
(1 RCT)

⊕⊕⊝⊝
LOW ²

SF‐36 vitality subscale scores ranged from 0 to 100, with higher scores indicating greater vitality (less fatigue).

Quality of life
assessed with: IBDQ
follow‐up: 56 weeks

The mean quality of life score was 172.9

MD 9.4 higher
(1.63 lower to 20.43 higher)

‐

147
(1 RCT)

⊕⊕⊝⊝
LOW²

IBDQ scores ranged from 32 to 224, with higher scores indicating better quality of life.

Adverse events
assessed with: MedDRA
follow‐up: 56 weeks

847 per 1,000

856 per 1,000
(785 to 906)

OR 1.08
(0.66 to 1.75)

518
(1 RCT)

⊕⊕⊕⊝
MODERATE ³

Serious adverse events
assessed with: MedDRA
follow‐up: 56 weeks

153 per 1,000

81 per 1,000
(48 to 135)

OR 0.49
(0.28 to 0.86)

518
(1 RCT)

⊕⊕⊕⊝
MODERATE ³

Withdrawal due to adverse events
assessed with: MedDRA
follow‐up: 56 weeks

134 per 1,000

47 per 1,000
(24 to 88)

OR 0.33
(0.15 to 0.70)

518
(1 RCT)

⊕⊕⊕⊝
MODERATE ³

*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; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: 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: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Adalimumab maintenance compared to placebo for fatigue in inflammatory bowel disease

Patient or population: participants with moderately‐to‐severely active Crohn's disease
Setting: 92 centres in the United States, Europe, Canada, Australia and South Africa
Intervention: adalimumab maintenance
Comparison: placebo

Outcomes

Anticipated absolute effects^* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo

Risk with adalimumab maintenance

Fatigue
assessed with: SF‐36 Vitality
follow‐up: 56 weeks

The mean fatigue score was 54.8

MD 3 higher
(4.25 lower to 10.25 higher)

‐

246
(1 RCT)

⊕⊕⊝⊝
LOW ¹

SF‐36 vitality subscale scores ranged from 0 to 100, with higher scores indicating better vitality (less fatigue).

Quality of life
assessed with: SF‐36 Physical Component Summary
follow‐up: 56 weeks

The mean quality of life score was 47.7

MD 1.3 higher
(1.3 lower to 3.99 higher)

‐

240
(1 RCT)

⊕⊕⊝⊝
LOW ¹

SF‐36 physical component summary scores ranged from 0 to 100, with higher scores indicating better physical quality of life.

Quality of life
assessed with: SF‐36 Mental Component Summary
follow‐up: 56 weeks

The mean quality of life score was 48.1

MD 2.2 higher
(1.28 lower to 5.68 higher)

‐

240
(1 RCT)

⊕⊕⊝⊝
LOW ¹

The SF‐36 mental component summary scores ranged from 0 to 100, with higher scores indicating better mental quality of life.

Quality of life
assessed with: IBDQ
follow‐up: 56 weeks

The mean quality of life score was 172.9

MD 9.9 higher
(0.4 lower to 20.2 higher)

‐

250
(1 RCT)

⊕⊕⊝⊝
LOW ¹

IBDQ scores ranged from 32 to 224, with higher scores indicating better quality of life.

Adverse events
assessed with: MedDRA
follow‐up: 56 weeks

847 per 1,000

873 per 1,000
(817 to 913)

OR 1.24
(0.81 to 1.89)

521
(1 RCT)

⊕⊕⊕⊝
MODERATE ²

Serious adverse events
assessed with: MedDra
follow‐up: 56 weeks

153 per 1,000

88 per 1,000
(56 to 131)

OR 0.53
(0.33 to 0.83)

521
(1 RCT)

⊕⊕⊕⊝
MODERATE ²

Withdrawal due to adverse events
assessed with: MedDRA
follow‐up: 56 weeks

134 per 1,000

58 per 1,000
(36 to 93)

OR 0.40
(0.24 to 0.66)

521
(1 RCT)

⊕⊕⊕⊝
MODERATE ²

*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; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: 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: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

AndoSan compared to placebo for participants with mild‐to‐moderately active Crohn's disease

Patient or population: participants with mild‐to‐moderately active Crohn's disease
Setting: outpatients from a single centre in Oslo, Norway
Intervention: AndoSan
Comparison: placebo

Outcomes

Anticipated absolute effects^* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo

Risk with AndoSan

Fatigue
assessed with: Total Fatigue score
follow‐up: 21 days

The mean fatigue score was 16.13

MD 1.63 lower
(3.51 lower to 0.26 higher)

‐

100
(2 RCTs)

⊕⊕⊝⊝
LOW ^{1 2}

Total fatigue scores ranged from 0 to 33, with higher scores indicating greater fatigue.

Fatigue
assessed with: SF‐36 Vitality
follow‐up: 21 days

The mean fatigue score was 40.61

MD 3.68 higher
(1.64 lower to 9 higher)

‐

100
(2 RCTs)

⊕⊕⊝⊝
LOW ^{1 2}

SF‐36 vitality subscale scores ranged from 0 to 100, with higher scores indicating greater vitality (less fatigue).

Quality of life ‐ not measured

‐

‐

‐

‐

This outcome was not measured.

Adverse events ‐ not reported

‐

‐

‐

‐

This outcome was not reported.

Serious adverse events ‐ not reported

‐

‐

‐

‐

This outcome was not reported.

Withdrawal due to adverse events ‐ not reported

‐

‐

‐

‐

This outcome was not reported.

*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; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: 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: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Ferric maltol compared to placebo for participants in remission or mild‐to‐moderately active Crohn's disease

Patient or population: participants in remission or mild‐to‐moderately active Crohn's disease
Setting: outpatients from 4 centres in Austria, Germany, Hungary and the UK
Intervention: ferric maltol
Comparison: placebo

Outcomes

Anticipated absolute effects^* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with placebo

Risk with ferric maltol

Fatigue
assessed with: SF‐36 vitality
follow‐up: 12 weeks

The mean fatigue score was 53.23

MD 9.31 lower
(17.15 lower to 1.47 lower)

‐

118
(1 RCT)

⊕⊕⊝⊝
LOW ¹

SF‐36 vitality subscale scores ranged from 0 to 100, with higher scores indicating greater vitality (less fatigue).

Quality of life
assessed with: IBDQ
follow‐up: 12 weeks

The mean quality of life score was 176

MD 3.7 higher
(7.89 lower to 15.29 higher)

‐

120
(1 RCT)

⊕⊕⊝⊝
LOW ¹

IBDQ scores ranged from 32 to 224, with higher scores indicating better quality of life.

Adverse events
assessed with: MedDRA
follow‐up: 12 weeks

717 per 1,000

582 per 1,000
(397 to 749)

OR 0.55
(0.26 to 1.18)

120
(1 RCT)

⊕⊕⊝⊝
LOW ¹

Serious adverse events
assessed with: MedDRA
follow‐up: mean 12 weeks

33 per 1,000

33 per 1,000
(5 to 202)

OR 1.00
(0.14 to 7.34)

124
(1 RCT)

⊕⊕⊝⊝
LOW ¹

Withdrawal due to adverse events
assessed with: MedDRA
follow‐up: 12 weeks

83 per 1,000

133 per 1,000
(45 to 334)

OR 1.69
(0.52 to 5.51)

120
(1 RCT)

⊕⊕⊝⊝
LOW ¹

*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; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: 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: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Guided stress management compared to conventional medical treatment for participants with Crohn's disease in remission

Patient or population: participants with Crohn's disease in remission
Setting: outpatients from a single centre in Spain
Intervention: guided stress management
Comparison: conventional medical treatment

Outcomes

Anticipated absolute effects^* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with conventional medical treatment

Risk with guided stress management

Fatigue
assessed with: Average frequency of tiredness
follow‐up: 12 months

The mean fatigue score was 51.4

MD 0
(30.77 lower to 30.77 higher)

‐

30
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{1 2}

The average frequency of tiredness was calculated as the number of symptomatic days divided by total reported days x 100. Higher mean scores indicated higher average frequency of tiredness.

Fatigue
assessed with: Severity of tiredness
follow‐up: 12 months

The mean fatigue score was 1

MD 0.3 higher
(0.39 lower to 0.99 higher)

‐

30
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{1 2}

The severity of tiredness scores ranged from 0 to 3, with higher scores indicating greater severity of tiredness.

Quality of life ‐ not measured

‐

‐

‐

‐

This outcome was not measured.

Adverse events ‐ not measured

‐

‐

‐

‐

This outcome was not measured.

Serious adverse events ‐ not measured

‐

‐

‐

‐

This outcome was not measured.

Withdrawal due to adverse events ‐ not measured

‐

‐

‐

‐

This outcome was not measured.

*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; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: 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: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Self‐directed stress management compared to conventional medical treatment for participants with Crohn's disease in remission

Patient or population: participants with Crohn's disease in remission
Setting: outpatients from a single centre in Spain
Intervention: self‐directed stress management
Comparison: conventional medical treatment

Outcomes

Anticipated absolute effects^* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Risk with conventional medical treatment

Risk with self‐directed stress management

Fatigue
assessed with: Average frequency symptom (tiredness)
follow‐up: 12 months

The mean fatigue score was 51.4

MD 29.6 lower
(58.68 lower to 0.52 lower)

‐

30
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{1 2}

The average frequency symptom (tiredness) was calculated as the number of symptomatic days divided by the total reported days x 100. Higher scores indicated greater average frequency of tiredness.

Fatigue
assessed with: Severity of tiredness
follow‐up: 12 months

The mean fatigue score was 1

MD 0.3 lower
(0.98 lower to 0.38 higher)

‐

30
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{1 2}

Severity of tiredness scores ranged from 0 to 3, with higher scores indicating greater severity of tiredness.

Quality of life ‐ not measured

‐

‐

‐

‐

This outcome was not measured.

Adverse events ‐ not measured

‐

‐

‐

‐

This outcome was not measured.

Serious adverse events ‐ not measured

‐

‐

‐

‐

This outcome was not measured.

Withdrawal due to adverse events ‐ not measured

‐

‐

‐

‐

This outcome was not measured.

*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; RR: Risk ratio; OR: Odds ratio;

GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: 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: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect