Efficacy and safety of JAK inhibitors in the treatment of psoriasis and psoriatic arthritis: a systematic review and meta-analysis

Abstract

Background JAK inhibitors are a relatively new class of medications that may be useful in the treatment of moderate-to-severe psoriasis and psoriatic arthritis (PsA). The objective of this study was to determine the efficacy of several JAK inhibitors in treating psoriasis and PsA and examine safety concerns. Methods MEDLINE, Cochrane and EMBASE were searched for randomized controlled trials and observational studies comparing any JAK inhibitor to placebo. The primary outcomes were a 75% improvement in the Psoriasis Area and Severity Index (PASI75) and a 20% improvement in the American College of Rheumatology composite score (ACR20). A secondary outcome was the proportion of patients achieving a “0” or “1” on the static Physician Global Assessment scale. Odds ratios were used to compare the proportion of patients reaching these targets in the max dose intervention group vs. the placebo group. A random effects model was used to account for heterogeneity. Results In total, 15 RCTs were included in the study and no observational studies. This encompassed 6757 patients in total. When the results were combined, the calculated odds ratio for PASI75 amongst tofacitinib vs. placebo was OR 14.35 [95%CI 7.65, 26.90], for PASI75 amongst non-tofacitinib JAK inhibitors vs. placebo it was OR 6.42 [95%CI 4.89, 8.43], for ACR20 amongst all JAK inhibitors versus placebo was OR 5.87 [95%CI 4.39, 7.85]. There was no significant difference in prevalence of serious adverse events between intervention and control in any of these studies. Conclusion JAK inhibitors show promise for safely treating moderate-to-severe psoriasis and psoriatic arthritis.

Comparing Meta-Analyses with ChatGPT in the Evaluation of the Effectiveness and Tolerance of Systemic Therapies in Moderate-to-Severe Plaque Psoriasis

“…We identified 28 MAs/NMAs published between January 2021 and May 2023, investigating and comparing the effect of systemic therapies for moderate-to-severe adult plaque psoriasis [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. A total of 10 analyses were excluded for the following reasons: insufficient information on the compared therapies in the abstract, the absence of the full text [ 28 , 29 , 30 ], the full text being in a language other than English [ 31 ], being a comparison to a placebo [ 32 , 33 , 34 , 35 , 36 ], or the absence of a direct comparison between therapies [ 37 ]. Two older versions or corrections of older MAs were also excluded [ 38 , 39 ] ( Figure 1 ).…”

Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice

“…Data from our preclinical studies suggest that there is modulation of the adaptive immune cell repertoire, but whether this is a persistent effect remains to be tested. The application of JAK and TYK2 inhibitors in other autoimmune conditions suggests chronic dosing would likely be necessary (78,79). Notwithstanding these unresolved questions, our results underscore the diverse and beneficial effects of TYK2 inhibition at the level of the β cell and the immune system in pre-clinical models of T1D, strongly supporting the rationale for testing these agents as a novel therapy to preserve β cells in T1D.…”

“…Data from our preclinical studies suggest that there is modulation of the adaptive immune cell repertoire, but whether this is a persistent effect remains to be tested. The application of JAK and TYK2 inhibitors in other autoimmune conditions suggests chronic dosing would likely be necessary (78,79).…”

Pityriasis rubra pilaris partially responsive to treatment with upadacitinib: A case report

“…The use of JAK inhibitors has not been investigated in the management of PRP. However, there is increasing evidence, including randomized, double-blinded, and placebo-controlled clinical trials, supporting the use of JAK inhibitors in other inflammatory dermatoses such as atopic dermatitis and psoriasis, [14][15][16] which share many clinical and histological features with PRP. Pro-inflammatory cytokines involved in the pathogenesis of psoriasis and atopic dermatitis, such as IL-12/IL-23 and IL-4/IL-13/IL-31, respectively, act via JAK/ STAT signaling pathways.…”