Key messages
- After six months of treatment, medicines called 'biologics' seem to work best to clear patches of psoriasis on the skin.
- Longer studies are needed to assess the benefits and potential harms of longer treatment with medicines that are injected or taken by mouth to treat psoriasis.
- More studies are needed that compare these types of medicines directly against each other.
What is psoriasis?
Psoriasis is an immune condition that affects the skin and, sometimes, the joints. Psoriasis speeds up the production of new skin cells, which build up to form raised patches on the skin known as 'plaques'. Plaques can also be flaky, scaly, itchy, and appear red on white skin, and as darker patches on darker skin tones. Plaque psoriasis is the most common form of psoriasis.
How is psoriasis treated?
Treatments for psoriasis depend on how bad the symptoms are. Around 10% to 20% of people with moderate or severe psoriasis will need to take medicines that affect their immune system, to help control the psoriasis. These medicines are called systemic treatments, because they affect the whole body. These are usually taken by mouth (orally) or injected.
Why did we do this Cochrane Review?
There are three different types of systemic medicines to treat psoriasis:
- 'biologics' – proteins, such as antibodies, that target interleukins and cytokines (parts of the immune system that affect how cells behave);
- small molecules – organic compounds that affect immune cells (examples include apremilast); and
- non-biologic medicines – medicines that have been in use for a long time to treat psoriasis, such as methotrexate, ciclosporin, and retinoids.
We wanted to find out about the benefits and potential harms of taking systemic medicines to treat psoriasis, and to see if some medicines work better than others.
What did we do?
We searched for studies that tested systemic medicines to treat plaque psoriasis.
How up to date is this review?
We included evidence up to October 2022.
What did we find?
We found 179 studies, including 12 new studies since our last search (October 2022). The studies tested 20 different medicines, covering 62,339 adults with psoriasis (average age 44.6 years) and lasted from two to six months. Of 149 studies that reported their source of funding, a pharmaceutical company provided funding for 138 studies and 11 were funded by non-commercial organisations or academic institutions.
Most studies compared the systemic medicine against a placebo (a 'dummy' treatment that does not contain any medicine but looks identical to the medicine being tested). They used a common measurement scale called the PASI (Psoriasis Area and Severity Index) to compare how well each medicine cleared psoriasis plaques from the skin, looking for a 90% improvement (called 'PASI 90'). Few studies reported on participants' well-being.
We compared all the medicines with each other using a mathematical method called a network meta-analysis.
What are the main results of our review?
All the medicines tested worked better than a placebo to treat psoriasis (measured as a 90% improvement in PASI).
Biologic medicines (that targeted interleukins 17, 23 and 12/23, and the cytokine TNF-alpha) treated psoriasis better than the non-biologic medicines.
Compared with placebo, four biologic medicines worked best to treat psoriasis, with little difference between them:
- infliximab (targets TNF-alpha);
- ixekizumab and bimekizumab (targets interleukin-17); and
- risankizumab (targets interleukin-23).
We found no significant difference in the numbers of serious unwanted events for all systemic medicines tested when compared with a placebo. However, the studies did not consistently report results about safety, such as serious unwanted events. We therefore could not create a reliable risk profile of systemic medicines.
Limitations of the evidence
We are confident in our results for the four biologic medicines (infliximab, ixekizumab, bimekizumab, and risankizumab) that worked best to treat psoriasis. We are less confident in our results for serious unwanted events, because of the low number of unwanted events reported.
We are also less confident in the results for the non-biologic medicines because of concerns about how some of the studies were conducted. Further research is likely to change these results.
We did not find many studies for some of the 20 medicines included in our review. Participants in the studies often had severe psoriasis at the start of the study, so our results may not be useful for people whose psoriasis is less severe. Our findings relate only to treatment with systemic medicines for up to six months at most.
Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence.
This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies 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 typical of patients seen in daily clinical practice.
We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was very low to moderate quality.
More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies is needed.
Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.
Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis.
To compare the benefits and harms of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their benefits and harms.
For this update of the living systematic review, we updated our searches of the following databases monthly to October 2022: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase.
Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation).
We conducted duplicate study selection, data extraction, risk of bias assessment, and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs).
We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing.
We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety).
This update includes an additional 12 studies, taking the total number of included studies to 179, and randomised participants to 62,339, 67.1% men, mainly recruited from hospitals. Average age was 44.6 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (56%). We assessed a total of 20 treatments. Most (152) trials were multicentric (two to 231 centres). One-third of the studies (65/179) had high risk of bias, 24 unclear risk, and most (90) low risk. Most studies (138/179) declared funding by a pharmaceutical company, and 24 studies did not report a funding source.
Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents.
For reaching PASI 90, the most effective drugs when 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), risankizumab (RR 26.16, 95% CI 22.03 to 31.07). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab and ixekizumab were significantly more likely to reach PASI 90 than secukinumab. Bimekizumab, ixekizumab, and risankizumab were significantly more likely to reach PASI 90 than brodalumab and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab, and brodalumab), and anti-IL23 drugs except tildrakizumab were significantly more likely to reach PASI 90 than ustekinumab, three anti-TNF alpha agents, and deucravacitinib. Ustekinumab was superior to certolizumab. Adalimumab, tildrakizumab, and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate.
We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with very low- to moderate-certainty evidence for all the comparisons. The findings therefore have to be viewed with caution.
For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions.