Table 2.
Summary of findings: fumaric acid esters (FAEs) vs. methotrexate (MTX). Patient or population: psoriasis in adults. Setting: departments of dermatology, Rotterdam and Eindhoven, the Netherlands. Intervention: FAE 720 mg (after week 9, following the standard progressive dosage regimen). Comparison: oral MTX 15 mg weekly (following gradual dose increments)
| Outcomes | Anticipated absolute effects (95% CI)a | Relative effect (95% CI) | No. of participants (studies) | Quality of evidence (GRADE)b | Comments | |
|---|---|---|---|---|---|---|
| Risk with MTX | Risk with FAE | |||||
| PASI score; scale range from 0 to 72 (higher score indicates more severe psoriasis) | Mean PASI score was 6·7 | Mean PASI score in the intervention group was 3·8 more (0·68–6·92 more) | – | 51 (1 RCT) | ⨁◯◯◯; VERY LOWc , d , e | PASI score was measured at week 12. The study reported no significant difference between FAEs and MTX based on mean change from baseline |
| AEs leading to treatment discontinuation | Moderate | RR 0·19 (0·02–1·53) | 51 (1 RCT) | ⨁◯◯◯; VERY LOWc , d , e | Based on a small sample size (FAE 26, MTX 25). The main reasons were elevated liver enzymes with MTX and diarrhoea with FAEs. No serious AEs occurred in either group | |
| 20 per 100 | 4 per 100 (0–31) | |||||
| Quality of life: not measured | See comment | See comment | Not estimable | – | – | Quality of life was not assessed |
| Common nuisance AEs (not leading to treatment discontinuation) | Moderate | RR 0·89 (0·77–1·03) | 54 (1 RCT) | ⨁◯◯◯; VERY LOWc , d , e | Only flushing was significantly more reported with FAEs. Occurrences of other AEs including laboratory findings were not significantly different | |
| 100 per 100 | 89 per 100 (77–100) | |||||
| PASI 50 | Moderate | RR 0·71 (0·41–1·22) | 51 (1 RCT) | ⨁◯◯◯; VERY LOWc , d , e | Based on a small sample size (MTX 25, FAE 26) | |
| 60 per 100 | 43 per 100 (25–73) | |||||
| PASI 75 | Moderate | RR 0·80 (0·28–2·29) | 51 (1 RCT) | ⨁◯◯◯; VERY LOWc , d , e | Based on a small sample size (MTX 25, FAE 26) | |
| 24 per 100 | 19 per 100 (7–55) | |||||
| PASI 90 | Moderate | RR 0·48 (0·05–4·98) | 51 (1 RCT) | ⨁◯◯◯; VERY LOWc , d , e | Based on a small sample size (MTX 25, FAE 26) | |
| 8 per 100 | 4 per 100 (0–40) | |||||
AE, adverse effect; CI, confidence interval; PASI, Psoriasis Area and Severity Index; PASI 50, ≥ 50% improvement in PASI; RCT, randomized controlled trial; RR, risk ratio. aThe risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). bGRADE Working Group grades of evidence. High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate 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 quality: Our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of the effect. cDowngraded one level due to limitations in design; highest dose of MTX given was 15 mg per week while the maximum dose of FAEs was given. dDowngraded one level due to limitations in design; open‐label design (high risk of performance and detection bias). eDowngraded one level due to imprecision; small sample size.