More SAEs With Biologic Agents vs Placebo in Treatment of Psoriasis

The exclusion of patients with worsening psoriasis from meta-analyses of trials that examine biologic therapies for type-plaque psoriasis reveal that serious adverse events (SAEs) are higher with biologic therapies than placebo, which suggest that findings from many meta-analyses do not reflect the real-world safety of biologic agents for psoriasis. This is according to a study research published in the British Journal of Dermatology.

In this study, researchers from France analyzed 51 randomized clinical trials in the Living Network Cochrane Review that compared a biologic therapy to placebo in patients with moderate to severe plaque psoriasis who required systemic treatment (N=24,820).

Trials included in this analysis included ≥1 anti-tumor necrosis factor (TNF) alpha arm, 1 anti-interleukin (IL)-17 arm, 1 anti-IL-23 arm, and 1 anti-IL-12/23 arm. The primary outcome of the analysis included the number of SAEs with biologic agents vs placebo after cases of psoriasis worsening were excluded. An additional secondary outcome included the number of adverse events (AEs) of special interest.

The mean age of the overall population was 45 years, and the mean baseline PASI score was 20.5. A higher percentage of patients included in all 51 trial were men compared with women (69% vs 31%, respectively). Approximately 25% (n=6287) of the population were randomly assigned to a placebo group.

In the analysis that included cases of psoriasis worsening, there was no statistically significant difference between biologic therapies and placebo in terms of the risk for occurrence SAEs (risk ratio [RR], 1.09; 95% CI, 0.88-1.36; P =.43). When the investigators excluded cases of psoriasis worsening, however, biologicl therapy was associated with a significantly higher risk for SAEs (RR, 1.30; 95% CI, 1.02-1.65; P =.03).

Separated by drug classes, the analysis revealed RRs of 1.68 (95% CI, 1.11-2.54; P =.01) for anti-TNF-alpha, 1.28 (95% CI, 0.88-1.85; P =.20) for anti-IL-17, 0.95 (95% CI 0.59-1.52; P =.83) for anti-IL-23, and 1.18 (95% CI 0.72-1.94; P =.51) for anti-IL-12/23. The small number of AEs of special interest in these analyses prevented the researchers from examining this outcome.

According to the investigators, the reporting of psoriasis worsening has changed over time, which made indirect comparisons not possible by network meta-analysis.

Based on these findings, the investigators added that “the results for SAEs overall and SAEs excluding disease worsening should be presented in the results of RCTs and so in systematic reviews and meta-analyses.”


Afach S, Chaimani A, Evrenoglou T, et al. Meta-analysis results do not reflect the real safety of biologics in psoriasis [published online May 23, 2020]. Br J Dermatol. doi: 10.1111/bjd.19244