(34) Jak Inhibitors for Atopic Dermatitis: A Network Meta-Analysis of Adverse Events

Saturday, August 27, 2022

8:00 AM – 6:00 PM CEST

Location: Hall C

Publication Number: 708

Presenting Author(s)

Ana Penedones, PhD
– University of Coimbra, School of Pharmacy, Coimbra, Portugal

Co-Author(s)

Carlos Alves, PharmD, PhD
– University of Coimbra, School of Pharmacy, Coimbra, Coimbra, Portugal
Diogo Mendes
– University of Coimbra, Faculty of Pharmacy, Coimbra, Portugal
Francisco Batel Marques
– University of Coimbra, Faculty of Pharmacy, Coimbra, Portugal

Background: Atopic dermatitis is an inflammatory, chronic, relapsing, skin disease characterized by pruritus and eczematous lesions. The JAK inhibitors demonstrated to be efficacious in treating atopic dermatitis, but it is relevant to understand if there are significant differences between the safety profile of these drugs.

Objectives: This network meta-analysis is aimed at comparing the relative safety of the different JAK inhibitors in patients with atopic dermatitis.

Methods: Medline, EMBASE and clinicaltrials.gov were searched from its inception until February 17, 2022, for phase II or III, randomized controlled trials (RCTs) which have been designed to evaluate the efficacy and safety of JAK Inhibitors in patients with atopic dermatitis. The outcomes assessed were the risk of serious adverse events and adverse events leading to treatment discontinuation. For each outcome, treatments were ranked according to the probability of being the best (safest) alternative. Statistical analyses were conducted using WinBUGS version 1.4.3..

Results: A total of 28 RCTs retrieved from 25 publications were included. Compared with delgocitinib, baricitinib (Odds Ratio [OR] 3,69, 95% credible interval [CrI] 1,18 – 10,77), abrocitinib (OR 3.64, 95% CrI 1.15 - 10.54) and upadacitinib (OR 3.43, 95% CrI 1.06 - 10.11) increase the risk of serious adverse events. Delgocitinib was found to be the safest treatment, followed by tofacitinib and dupilumab. Regarding adverse events leading to treatment discontinuation, baricitinib (OR 6.47, 95% CrI 1.61 - 22.00), abrocitinib (OR 6.72, 95% CrI 1.71 - 22.38) and upadacitinib (OR 5.92, 95% CrI 1.47 - 20.15) presented an increased risk when compared with ruxolitinib. Identical results were found when delgocitinib was compared with baricitinib (OR 4.58, 95% CrI 1.26 - 14.97), abrocitinib (OR 4.76, 95% CrI 1.35 - 14.93) and upadacitinib (OR 4.18, 95% CrI 1.16 - 13.67). Ruxolitinib was found to be the safest treatment, followed by delgocitinib and tofacitinib.

Conclusions: The results suggest delgocitinib and ruxolitinib are the safest JAK inhibitors for patients with atopic dermatitis. Nevertheless, postmarketing pharmacovigilance evidence will be useful to confirm these findings.