Comparative efficacy and safety of Janus kinase inhibitors and biological disease-modifying antirheumatic drugs in rheumatoid arthritis: a systematic review and network meta-analysis

Abstract

Objective: To evaluate the comparative efficacy and safety of Janus kinase (JAK) inhibitors and biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) and an inadequate response to at least one disease-modifying antirheumatic drug (DMARD). Methods: PubMed, Embase, Cochrane library and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to April 2020. The active drugs included three JAK inhibitors and eight bDMARDs while the control drugs included placebo or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Outcomes include American College of Rheumatology 20% response (ACR20), Disease Activity Score in 28 joints (DAS28), Health Assessment Questionnaire–Disability Index (HAQ-DI) and discontinuations for adverse events (AEs). We estimated summary odds ratios (ORs) and weighted mean differences (WMDs) using network meta-analysis with random effects. Results: Eighty-eight RCTs with 31,566 patients were included. All JAK inhibitors and bDMARDs were more effective than placebo in ACR20 (ORs ranging between 3.05 and 5.61), DAS28 (WMDs ranging between −1.91 and −0.80) and HAQ-DI (WMDs ranging between −0.34 and −0.21). Tocilizumab, certolizumab pegol and upadacitinib showed relatively good efficacy in these three outcomes according to their relative ranking. Notably, tocilizumab was more effective than other active drugs in DAS28 (WMDs ranging between −1.11 and −0.49). Compared with the lower recommended doses, increasing the doses of JAK inhibitors (baricitinib 4 mg versus 2 mg, tofacitinib 10 mg versus 5 mg and upadacitinib 30 mg versus 15 mg) cannot provide significant additional benefits. In terms of discontinuations for AEs, all active drugs showed no significant difference compared with placebo except certolizumab pegol [OR 1.65, 95% credible interval (CrI) 1.06–2.61] and rituximab (3.17, 1.11–10.80). Conclusions: Tocilizumab, certolizumab pegol and upadacitinib may have relatively good efficacy in patients with RA after treatment failure with csDMARDs. RA patients taking a JAK inhibitor may have a preference for a lower recommended dose.

Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients

“…Importantly, the proportion of patients reaching remission assessed using the DAS28-CRP was significantly higher in the JAK group than in the case of bDMARDs, which is consistent with the findings of a previous meta-analysis demonstrating the superiority of upadacitinib compared to adalimumab [100]. However, no statistically significant differences were found in remission rates according to the DAS28-ESR, SDAI, and CDAI.…”

“…Previously, no other meta-analysis examined the effect of JAK inhibitors on PROs, however, some studies included outcomes regarding life quality. One analysis included an improvement in the HAQ-DI and found JAK inhibitors overall as effective as bDMARDs, except for tofacitinib 10 mg showing significant advantage compared to adalimumab and baricitinib 2 mg performing slightly worse than bDMARDs [100]. In our analysis, the different JAK inhibitors were pooled into one group and significant differences between JAK inhibitors versus bDMARDs were not observed either.…”

The role of upadacitinib in the treatment of moderate-to-severe active rheumatoid arthritis

“…In a recent systematic review and network meta-analysis (NMA), comparative efficacy and safety of JAK inhibitors and most of the available bDMARDs were evaluated in RA patients with an inadequate response to at least one DMARD. 27 ACR20, DAS28, and HAQ-DI were used as efficacy outcomes and discontinuations due to AEs for safety. Upadacitinib, tocilizumab, and certolizumab pegol showed relatively good efficacy in these three efficacy outcomes and increasing the doses of JAK inhibitors (baricitinib 4 mg versus 2 mg, tofacitinib 10 mg versus 5 mg, and upadacitinib 30 mg versus 15 mg) did not appear to provide significant additional benefits.…”

Transdermal delivery of inflammatory factors regulated drugs for rheumatoid arthritis

“…The results of in vitro permeation experiments demonstrated that the cumulative permeation and the permeation rates of SIN-MN were 5.31 times and 5.06 times that of sinomenine gel (SIN-G) respectively. Transdermal pharmacokinetic studies in mice showed that the area under the curve (AUC) 0-800 min of the skin and blood of the SIN-MN group were 1.43 times and 1.63 times higher than that of the SIN-G group, indicating that SIN-MN has the ability to enhance the transdermal absorption of the drug (Shu et al., 2020 ).…”