Oral 5‐ASA vs placebo for maintenance of remission in ulcerative colitis

Patient or population: people with quiescent UC
Settings: outpatient
Intervention: oral 5‐ASA
Comparison: placebo

Failure to maintain clinical or endoscopic remission

Follow‐up: 6–12 months

RR 0.68
(0.61 to 0.76)

1555
(8 studies)

⊕⊕⊕⊕
High

Clinical remission defined using the revised SDAI (rectal bleeding = 0, mucosal appearance ≤ 2).

Failure to adhere to study medication

Not reported.

Adverse events

Follow‐up: 6–12 months

RR 0.93
(0.73 to 1.18)

1132
(5 studies)

⊕⊕⊕⊝
Moderate^a

Common adverse events included headache, nausea, abdominal pain, dyspepsia, bloating, influenza syndrome, rhinitis, diarrhea, and nasopharyngitis.

Serious adverse events

Follow‐up: 6–12 months

RR 0.60

(0.19 to 1.84)

826

(3 studies)

⊕⊕⊝⊝
Low^b

Serious adverse events included UC aggravation, acute pancreatitis, moderate ventricular dysfunction, intestinal obstruction, and esophagitis.

Withdrawal due to adverse event

Follow‐up: 6–12 months

RR 1.22
(0.76 to 1.95)

1454
(7 studies)

⊕⊕⊕⊝
Moderate^c

Common adverse events leading to withdrawal included UC aggravation diarrhea, headache, and paresthesia.

Exclusion/withdrawal after entry

Follow‐up: 6–12 months

RR 1.13

(0.88 to 1.44)

1074

(5 studies)

⊕⊕⊕⊝
Moderate^d

—

*The basis for the assumed risk (e.g. the median control group risk across studies) come from control arm of meta‐analysis, based on included trials. The corresponding risk (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).

5‐ASA: 5‐aminosalicylic acid; CI: confidence interval; RR: risk ratio; SDAI: Sutherland Disease Activity Index; UC: ulcerative colitis.

GRADE Working Group grades of evidence
High certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low certainty: we are very uncertain about the estimate.

Oral 5‐ASA vs SASP for maintenance of remission in ulcerative colitis

Patient or population: people with quiescent ulcerative colitis
Settings: outpatient
Intervention: oral 5‐ASA
Comparison: SASP

Failure to maintain clinical or endoscopic remission

Follow‐up: 6–18 months

RR 1.14
(1.03 to 1.27)

1655
(12 studies)

⊕⊕⊕⊕
High

Clinical or endoscopic remission defined as the absence of colitis symptoms together with an absence of inflammation on sigmoidoscopy.

Failure to adhere to study medication

Not reported.

Adverse event

Follow‐up: 6–18 months

RR 1.07
(0.82 to 1.40)

1138
(7 studies)

⊕⊕⊕⊝
Moderate^a

Commonly reported adverse events in the SASP‐controlled trials included: headache, anorexia or appetite loss, nausea, vomiting, abdominal pain, dyspepsia, excessive flatus, bloating, urticaria, and rash.

Serious adverse events

Not reported.

Withdrawal due to adverse event

Follow‐up: 6–18 months

RR 1.27
(0.87 to 1.87)

1585
(10 studies)

⊕⊕⊕⊝
Moderate^b

Common adverse events leading to withdrawal included diarrhea, abdominal pain, indigestion, and rash.

Exclusion/withdrawal after entry

Follow‐up: 6–18 months

RR 1.30

(1.04 to 1.63)

1497

(9 studies)

⊕⊕⊕⊝
Moderate^c

—

*The basis for the assumed risk (e.g. the median control group risk across studies) come from control arm of meta‐analysis, based on included trials. The corresponding risk (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).

5‐ASA: 5‐aminosalicylic acid; CI: confidence interval; RR: risk ratio; SASP: sulfasalazine.

GRADE Working Group grades of evidence
High certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low certainty: we are very uncertain about the estimate.

Once‐daily dosing vs conventional dosing for maintenance of remission in ulcerative colitis

Patient or population: people with quiescent UC
Settings: outpatient
Intervention: OD oral 5‐ASA
Comparison: conventional dosing of 5‐ASA

Failure to maintain clinical or endoscopic remission

Follow‐up: 12–13 months

RR 0.94
(0.88 to 1.01)

3910
(10 studies)

⊕⊕⊕⊕
High

Clinical or endoscopic remission defined as a mucosal score of 0 or 1 (endoscopic remission), or a bloody stool score of 0 and an UC‐DAI < 2/Simple Clinical Colitis Activity Index score of ≤ 2 points (clinical remission).

Failure to adhere to study medication regimen

Follow‐up: 6–13 months

RR 1.18
(0.72 to 1.93)

2306
(9 studies)

⊕⊕⊕⊝
Moderate^a

Adherence to medication regimen calculated using objective data (pill count or pharmacy data) in 6/9 studies in the analysis. 2 studies used participant self‐report to calculate adherence and 1 study did not describe how adherence was assessed.

Adverse event

Follow‐up: 6–13 months

RR 0.98
(0.92 to 1.04)

3497
(8 studies)

⊕⊕⊕⊕
High

Common adverse events included flatulence, dyspepsia, abdominal pain, nausea, diarrhea, headache, nasopharyngitis, inflammation of the upper respiratory tract, gastroenteritis. dental caries, and worsening of UC.

Serious adverse events

Follow‐up: 6–13 months

RR 1.20

(0.77 to 1.87)

3196

(7 studies)

⊕⊕⊕⊝
Moderate^b

Serious adverse events included UC aggravation, acute pancreatitis, anal fistula, pneumonia, melena, nephrolithiasis, and hypersensitivity pneumonitis.

Withdrawal due to adverse events

Follow‐up: 6–13 months

RR 1.18
(0.74 to 1.89)

4340
(8 studies)

⊕⊝⊝⊝
Very low^c,d

Adverse events leading to withdrawal included UC aggravation, flatulence, nausea, and abdominal distension.

Exclusion/withdrawal after entry

Follow‐up: 6–13 months

RR 0.99

(0.85 to 1.15)

3737

(7 studies)

⊕⊕⊕⊕
High

—

*The basis for the assumed risk (e.g. the median control group risk across studies) come from control arm of meta‐analysis, based on included trials. The corresponding risk (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).

5‐ASA: 5‐aminosalicylic acid; CI: confidence interval; OD: once daily; RR: risk ratio; SDAI: Sutherland Disease Activity Index; UC: ulcerative colitis; UC‐DAI: Ulcerative Colitis Disease Activity Index.

GRADE Working Group grades of evidence
High certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low certainty: we are very uncertain about the estimate.

Oral 5‐ASA vs comparator 5‐ASA formulation for maintenance of remission in ulcerative colitis

Patient or population: people with quiescent UC
Settings: outpatient
Intervention: oral 5‐ASA (balsalazide, Pentasa and olsalazine)
Comparison: comparator oral 5‐ASA (Asacol and Salofalk)

Failure to maintain clinical or endoscopic remission

Follow‐up: 6–18 months

RR 1.08
(0.91 to 1.28)

707
(6 studies)

⊕⊕⊝⊝
Low^a,b

Clinical or endoscopic remission was defined as either the Harvey Bradshaw Index (score < 3) and by a sigmoidoscopy (score 0–1) or the absence of symptoms or the presence of only mild symptoms.

Failure to adhere to study medication regimen

Not reported.

Adverse event

Follow‐up: 6–12 months

RR 0.94
(0.83 to 1.07)

357
(4 studies)

⊕⊕⊝⊝
Low^c,d

Common adverse events included dyspepsia, abdominal pain, nausea, distension, diarrhea, headache, nasopharyngitis or respiratory infections, influenza‐like disorder, and rash.

Serious adverse events

Follow‐up: 12 months

RR 0.56

(0.14 to 2.22)

95

(1 study)

⊕⊕⊝⊝
Low^e

Serious adverse events reported included urinary tract infection, severe complication of UC, cardiac arrest, ischemic heart, fracture of the scaphoid, and spigelian hernia.

Withdrawal due to adverse events

Follow‐up: 6–12 months

RR 1.25
(0.0.56 to 2.78)

457
(5 studies)

⊕⊝⊝⊝
Verylow^f,g

Common adverse events leading to withdrawal included headache, lethargy, hypertension, malaise, and abdominal pain.

Exclusion/withdrawal after entry

Follow‐up: 6–12 months

RR 1.23

(0.90 to 1.70)

457

(5 studies)

⊕⊕⊕⊝
Moderate^h

—

*The basis for the assumed risk (e.g. the median control group risk across studies) come from control arm of meta‐analysis, based on included trials. The corresponding risk (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).

5‐ASA: 5‐aminosalicylic acid; CI: confidence interval; OD: once daily; RR: risk ratio; SDAI: Sutherland Disease Activity Index; UC: ulcerative colitis.

GRADE Working Group grades of evidence
High certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low certainty: we are very uncertain about the estimate.