Key messages
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Background
Psoriasis is an immune-mediated disease with skin or joint manifestations, or both, and has a significant impact on quality of life. Although there is currently no cure for psoriasis, there are various treatment strategies that allow you to maintain control of the signs and symptoms of the disease. The relative beneficial effect of these treatments is still unclear due to the limited number of trials that directly compare them, so it was decided to perform a network meta-analysis.
Goals
To compare the benefits and harms of nonbiological systemic agents, small molecules, and biological treatments in people with moderate to severe psoriasis using a network meta-analysis, and to establish a classification of these treatments based on their benefits and harms.
Search methods
For this update of this ongoing systematic review, the following databases were searched monthly until October 2022: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase.
Selection criteria
Randomized controlled trials (RCTs) of systemic treatments in adults over 18 years of age with moderate to severe plaque psoriasis, at any stage of treatment, compared with placebo or another active drug. The main outcomes were: proportion of participants achieving lesion-free or almost lesion-free skin, that is, at least a Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) in the induction phase (eight to 24 weeks after randomization).
Data collection and analysis
Study selection, data extraction, risk of bias assessment and analyzes were performed in duplicate. Data were summarized using network meta-analysis (MAR) and paired meta-analysis to compare treatments and classify them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs).
The certainty of the MAR evidence for the two main outcomes and all comparisons was considered very low, low, moderate or high, according to CINeMA. When data were unclear or missing, study authors were contacted.
The area under the cumulative classification curve (SUCRA) was used to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety).
Main results
This update included 12 additional studies, increasing the total number of included studies to 179 and the number of randomized participants to 62,339, 67.1% men, primarily recruited from hospitals. The mean age was 44.6 years, the mean PASI score at baseline was 20.4 (range: 9.5 to 39).
Most studies were placebo-controlled (56%). A total of 20 treatments were evaluated. The majority (152) of the trials were multicentre (two at 231 centres). One third of the studies (65/179) had a high risk of bias; 24, an uncertain risk and the majority (90) a low risk. The majority of studies (138/179) reported receiving funding from a pharmaceutical company and 24 studies did not report a funding source.
Class-level network meta-analysis showed that all interventions (non-biological systemic drugs, small molecules, and biologic treatments) had a higher percentage of patients achieving PASI 90 compared to placebo.
Treatment with an IL 17 inhibitor (anti‐IL 17) showed a higher percentage of patients achieving PASI score 90 compared to all interventions. Biological treatments that inhibit IL 17, IL 12/23, IL 23 and TNF alpha showed a higher percentage of patients achieving a PASI 90 than non-biological systemic drugs.
To achieve PASI 90, the most effective drugs compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio [RR] 49.16, 95% CI 20.49 to 117.95), bimekizumab (RR 27.86, 95% CI 23.56 to 32.94), ixekizumab (RR 27.35, 95% CI 23.15 to 32.29 ) , RR 26.16, 95% CI: 22.03 to 31.07). The clinical effectiveness of these drugs was similar when compared to each other.
Bimekizumab and ixekizumab were significantly more likely to achieve PASI 90 than secukinumab. Bimekizumab, ixekizumab, and Risankizumab were significantly more likely to achieve PASI 90 than brodalumab and guselkumab. Infliximab, anti‐IL 17 drugs (bimekizumab, ixekizumab, secukinumab, and brodalumab), and anti‐IL 23 drugs except tildrakizumab were significantly more likely to achieve a PASI 90 than ustekinumab, three anti‐TNF alfa agents, and deucravacitinib. Ustekinumab was superior to certolizumab. Adalimumab, tildrakizumab and ustekinumab were superior to etanercept. No significant differences were observed between apremilast and two non-biological drugs: cyclosporine and methotrexate.
No significant differences were found between any of the interventions and placebo in the risk of serious adverse events (SAEs). The risk of SAEs was significantly lower in participants receiving methotrexate compared to most interventions. However, the SAE analyzes were based on a very small number of events with low to moderate certainty evidence for all comparisons. Therefore, the findings should be considered with caution.
Regarding the other efficacy outcomes (PASI 75 and Physician Global Assessment [PGA] 0/1), the results were very similar to the results for the PASI 90. Information on quality of life was often poorly provided and there were none in the case of several of the interventions.
Authors’ conclusions
This review shows that, compared with placebo, the biologics infliximab, bimekizumab, ixekizumab and Risankizumab were the most effective treatments in achieving a PASI score 90 in people with moderate to severe psoriasis based on high-certainty evidence.
This network meta-analysis (MAR) evidence is limited to induction treatment (outcomes measured from eight to 24 weeks after randomization) and is not sufficient to evaluate longer-term outcomes in this chronic disease. Furthermore, few studies were found for some of the interventions, and the young age (mean 44.6 years) and high level of disease severity (PASI 20.4 at baseline) may not be characteristic of the patients. attended to in daily clinical practice.
No significant differences were found between the interventions evaluated and placebo in terms of SAEs and the evidence on the safety of most interventions was of very low to moderate quality.
More randomized trials are needed that directly compare active agents and include systematic subgroup analyzes (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of the treatments included in this review, an evaluation of non-randomized studies is needed.
Editorial note : This is an ongoing systematic review. Continuous systematic reviews offer a new approach to updating reviews, in which the review is continually updated, incorporating new relevant evidence as it becomes available. Check the current status of this review in the Cochrane Database of Systematic Reviews.
