Table 1.
Summary of findings: fumaric acid esters (FAEs) vs. placebo. Patient or population: psoriasis in adults. Setting: two reports from the Netherlands, one from Poland and two international multicentre studies. Intervention: FAE. Comparison: placebo
| Outcomes | Anticipated absolute effects (95% CI)a | Relative effect (95% CI) | No. of participants (studies) | Quality of evidence (GRADE)b | Comments | |
|---|---|---|---|---|---|---|
| Risk with placebo | Risk with FAEs | |||||
| PASI score; scale range from 0 to 72 (higher score indicates more severe psoriasis) | PASI score reduced from a mean of 21·57 to 10·77 (FAE) and remained constant (placebo) (1 study, 99 participants, P < 0·001); median reduction of 71% (FAE) and 6% (placebo) (1 study, 144 participants, P < 0·001); median reduction of 67·8% (FAE) and 10·2% (placebo) (1 study, 175 participants, P < 0·001) | 418 (3 RCTs) | ⨁⨁◯◯; LOWc , d | All three studies reported significant benefit with FAEs, at week 12 (one study) and week 16 (two studies), but data could not be pooled in a meta‐analysis due to different ways of PASI score reporting | ||
| AEs leading to treatment discontinuation | Two participants withdrew from the FAE group (n = 13) compared with no dropouts in the placebo group (n = 14) (RR 5·36, 95% CI 0·28–102·12) | 27 (1 RCT) | ⨁◯◯◯; VERY LOWe , f | Outcome reported at week 16. Unclear whether any of the reported AEs were ‘serious’ | ||
| QoL assessed with Skindex‐29 (range 0–100; higher scores indicate lower level of QoL) | Mean scores reduced from 54·7 at baseline to 27·0 at week 16 in the FAE group (n = 105) and from 54·0 to 51·1 in the placebo group (n = 70) (P < 0·001) | 175 (1 RCT) | ⨁⨁◯◯; LOWc , g | The reporting abstract did not provide the statistical values needed to calculate the mean difference with 95% CI | ||
| Common nuisance AEs (not leading to treatment discontinuation) | Moderate | RR 4·72 (2·45–9·08) | 99 (1 RCT) | ⨁⨁⨁◯; MODERATEc | Most commonly stomach ache or cramps, diarrhoea and flushing | |
| 16 per 100 | 76 per 100 (39–100) | |||||
| PASI 50 | Moderate | RR 4·55 (2·80–7·40) | 247 (2 RCTs) | ⨁⨁◯◯; LOWc , g | The meta‐analysis included participants who received dimethylfumarate 720 mg | |
| 14 per 100 | 64 per 100 (39–100) | |||||
| PASI 75 | PASI 75 was attained by 39% of participants in the FAE group (n = 105) and 1% of those on placebo (n = 70) (1 study, week 16); and by 42% on FAE (n = 36) compared with 11% on placebo (n = 36) (1 study, week 12) | 247 (2 RCTs) | ⨁⨁◯◯; LOWc , g | Reported to be a statistically significant difference but data not pooled because of significant heterogeneity (I 2 = 77%) | ||
| PASI 90 (not measured) | See comment | See comment | Not estimable | – | – | Not measured in the included studies |
AE, adverse effect; CI, confidence interval; PASI, Psoriasis Area and Severity Index; PASI 50, ≥ 50% improvement in PASI; QoL, quality of Life; 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 limitations in design; high risk of performance and detection bias. dDowngraded one level due to risk of publication bias; data obtained from abstract(s), full report(s) not available. eDowngraded one level due to indirectness; the study was designed for psoriatic arthritis where all participants also had psoriasis, so may not be directly applicable to those with moderate‐to‐severe psoriasis. fDowngraded two levels for imprecision; small sample size and very wide CIs that included the possibility of an effect in either direction (crosses line of no effect). gDowngraded one level due to risk of bias; insufficient reporting.