Safety and Benefit–Risk Profile of Biologics and Oral Treatments for Moderate-to-Severe Plaque Psoriasis Journal of the American Academy of Dermatology

TAKE-HOME MESSAGE

• In this network meta-analysis of 59 randomized controlled trials of systemic treatments for moderate-to-severe psoriasis, the rates of adverse events (AEs) in short-term trials were lowest for tildrakizumab (46.0%), certolizumab (46.2%), and etanercept (49.1%). The rates of serious AEs were lowest for certolizumab (0.8%), risankizumab (1.2%) and etanercept (1.6%). The rates of AEs leading to discontinuation of treatment were lowest for risankizumab (0.5%), tildrakizumab (1.0%) and guselkumab (1.5%). Overall, risankizumab had the lowest rates of all outcomes and the most favorable benefit–risk profile. 

• Anti–IL-23 agents had the lowest rate of AEs and risankizumab was associated with the most favorable risk–benefit profile among patients with moderate-to-severe psoriasis treatments in clinical trials.

– Kelly B. Scarberry, MD

Written by

 

 

Lawrence J. GreenMD,FAAD

A network meta-analysis of between 45 and 52 phase II–IV studies of AEs, SAEs, and AEs leading to discontinuation in the first 12 to 16 weeks of therapy was performed comparing approved biologics, apremilast, and dimethyl fumarate (some studies did not report all the types of AEs analyzed). Further, a risk–benefit analysis comparing PASI 90 with the same risks as just mentioned was also performed; 6 to 7 studies met the authors criteria for a "long-term" (up to 13 months of therapy) meta-analysis of AEs, SAEs, and AEs leading to discontinuation and a similar risk–benefit analysis. In general, all biologics performed well with regard to risks and benefit–risk ratio. Tildrakizumab, certolizumab, and risankizumab were all associated with statistically significantly lower odds of experiencing any AEs compared with other biologics and the two oral agents. The treatments associated with the lowest rates of SAEs were certolizumab, risankizumab, and etanercept. Risankizumab was associated with statistically significantly lower odds of AEs leading to treatment discontinuation compared with other biologics and the two oral agents. Evaluating the long-term data, risankizumab and then guselkumab had a higher benefit–risk ratio than anti–IL-17s and TNF inhibitors.

As the authors mention, comparing different studies performed at different times over about a 25-year period, with different patient populations, and where safety measurements were taken at different time endpoints are limiting factors in interpretation of this meta-analysis. Comparison of specific AEs such as infection or malignancy was not possible in the meta-analysis. In addition, AEs, SAEs, and AEs leading to discontinuation are not always study medication–related, so analyzing them without knowing the relationship to the study medication is another limiting factor. Although it does not affect the interpretation/analysis of data or study conclusions, it is noteworthy that the study sponsor is the manufacturer of risankizumab.

Abstract 

BACKGROUND

The comparative safety and benefit-risk profiles of moderate-to-severe psoriasis treatments have not been well studied.

OBJECTIVE

To compare the short-term (12-16 weeks) and long-term (48-56 weeks) safety and benefit-risk profiles of moderate-to-severe psoriasis treatments.

METHODS

A systematic literature review of Phase II-IV randomized controlled trials (RCTs) of moderate-to-severe psoriasis treatments was conducted (cut-off: 07/01/2020). Any adverse events (AE), any serious AE (SAE), and AEs leading to treatment discontinuation were compared with Bayesian network meta-analyses (NMAs).

RESULTS

52 and 7 RCTs were included in the short- and long-term NMAs. In the short term, the rates of any AEs were lowest for tildrakizumab (posterior median: 46.0%), certolizumab (46.2%), and etanercept (49.1%). The rates of any SAE were lowest for certolizumab (0.8%), risankizumab (1.2%), and etanercept (1.6%). The rates of AEs leading to treatment discontinuation were lowest for risankizumab (0.5%), tildrakizumab (1.0%), and guselkumab (1.5%). In the long term, risankizumab had the lowest rates of all three outcomes (67.5%, 4.4% and 1.0%, respectively) and the most favorable benefit-risk profile.

LIMITATIONS

The results may not be generalizable to real world populations.

CONCLUSIONS

Anti-IL-23 agents were associated with low rates of safety events. Risankizumab had the most favorable benefit-risk profile in the long term.

Journal of the American Academy of Dermatology

Comparative Safety and Benefit-Risk Profile of Biologics and Oral Treatments for Moderate-to-Severe Plaque Psoriasis: A Network Meta-Analysis of Clinical Trial Data

J Am Acad Dermatol 2021 Feb 22;[EPub Ahead of Print], NH Shear, KA Betts, AM Soliman, A Joshi, Y Wang, J Zhao, P Gisondi, R Sinvhal, AW Armstrong 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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