Time to Onset of Action for Biologics and Targeted Treatments in Psoriasis: Systematic Targeted Literature Review and Network Meta-Analysis

For some patients with plaque psoriasis (PsO), a rapid response (i.e. short interval to time to onset of action [TOA]) is desired. The primary objective was to determine average time to achieve a Psoriasis Area and Severity Index (PASI) 90 response (50% of patients) for individual biologics or targeted therapies. Secondary outcomes included the average time to achieve a PASI 75 response (50% of patients), as well as PASI 90 and PASI 75 responses over the first 16 weeks of therapy. A systematic targeted literature review was conducted to identify phase III and IV randomised, double-blinded trials according to pre-specified eligibility criteria that investigated interleukin (IL)-12/23 inhibitors, IL-17 inhibitors, IL-23 inhibitors, Janus kinase (JAK) inhibitors, and phosphodiesterase (PDE) inhibitors. Using proportions of patients achieving PASI 90 or 75 responses over 16 weeks, network meta-analyses were conducted to estimate response over time. This was presented as curves, and TOA was summarized as median time to reach the 50th percentile. Forty-five trials were included in the main analyses. The IL-17 inhibitors bimekizumab, ixekizumab, brodalumab, and secukinumab 300 mg were estimated to provide the earliest onset of PASI 90 response at approximately 6 to 8 weeks. This was followed by the IL-23 inhibitors risankizumab and guselkumab at approximately 9–10 weeks, and the IL-12/23 inhibitor at 11–12 weeks. Although wide and overlapping credible intervals and similar point estimates were observed, these results suggest onset of action does not vary greatly across biologics in these classes. Onset of PASI 90 response could not be estimated by the model for tildrakizumab, and JAK and PDE4 inhibitors. Onset of PASI 75 response showed similar trends to PASI 90 response. IL-17 inhibitors, followed by IL-23 inhibitors, have the most rapid TOA among PsO biologics evaluated; any differences in onset of action between specific agents within the same drug class are not statistically or clinically significant. These analyses will allow clinicians to make more informed treatment decisions for their patients. Moderate-to-severe plaque psoriasis is a chronic condition that affects approximately 125 million people worldwide. The skin lesions in plaque psoriasis are red, scaly, and often itchy. In addition, patients with plaque psoriasis may have reduced quality of life. As an increasing number of treatments have become available for managing plaque psoriasis, determining the most appropriate therapy for individual patients can be complex. When making treatment decisions, clinicians consider several factors, including how long it will take for a patient to see clinical benefit from a treatment, otherwise known as time to onset of action. The time to onset of action of a treatment is determined by analysing changes in Psoriasis Area and Severity Index (PASI), a commonly used tool to assess the severity of psoriasis, over time. Commonly assessed outcomes in psoriasis clinical trials include a 90% and a 75% reduction in PASI scores (i.e. PASI 90 and PASI 75, respectively). We aimed to assess the average time to onset of action of various psoriasis treatments using data reported from 45 clinical trials. The proportion of patients achieving a PASI 75 or 90 response by week 16 was used in the analysis. Interleukin-17 inhibitors, followed by interleukin-23 inhibitors, generally had the fastest time to onset of action with respect to PASI response, while interleukin-12/23 inhibitors, followed by Janus kinase and phosphodiesterase 4 inhibitors, were slower.

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