The Efficacy and Safety of Mainstream Medications for Patients With cDMARD-Naïve Rheumatoid Arthritis: A Network Meta-Analysis

Abstract

Background: The mainstream medications for rheumatoid arthritis (RA) include conventional disease-modifying antirheumatic drugs (cDMARDs), which mostly are methotrexate (MTX), and biologic agents such as adalimumab (ADA), certolizumab (CZP), etanercept (ETN), golimumab (GOL), infliximab (IFX), and tocilizumab (TCZ). This network meta-analysis was aimed at evaluating the efficacy and safety of the medications above and interventions combining cDMARDs and biologic agents for patients with RA.Methods: PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched systematically for eligible randomized controlled trials (RCTs). Outcomes concerning efficacy and safety were evaluated utilizing odds ratios (ORs) and 95% credible intervals (CrI). The outcomes of efficacy would be evaluated through remission and American College of Rheumatology (ACR) scores. The surface under the cumulative ranking curve (SUCRA) was calculated to rank each treatment on each index.Results: A total of 20 RCTs with 9,047 patients were included, and the efficacy and safety of the concerning interventions for RA were evaluated. Compared with cDMARDs alone, TCZ+MTX, ETN+MTX, IFX+MTX, TCZ, and ADA+MTX showed significant statistical advantage on ACR20, ACR50, and ACR70. Apart from that, as for remission, TCZ+MTX, IFX+MTX, TCZ, and CZP+MTX performed better compared to cDMARDs alone. The SUCRA ranking also indicated that TCZ+MTX was the intervention with best ranking in the entire four efficacy indexes followed by ETX+MTX and IFX+MTX. However, there was no obvious difference among these medications compared with cDMARDs when it comes to safety, which need more specific studies on that.Conclusion: TCZ+MTX was potentially the most recommended combination of medications for RA due to its good performance in all outcomes of efficacy. ETX+MTX and IFX+MTX, which also performed well, could be introduced as alternative treatments. However, considering the adverse events, the treatments concerning should be introduced with caution.

Differential long-term retention of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis by age group from the FIRST registry

“…In this study, the retention rate of TCZ was high in all age groups, particularly in patients aged <65 years, and remained high in those aged ≥65 years. In a meta-analysis of studies on RA, TCZ and MTX combination was identi ed as the best intervention [37]. TCZ showed higher retention rates than TNFi and ABA in other studies [38,39], which supports the results of this study.…”

Two-year cost-effectiveness of different COBRA-like intensive remission induction schemes in early rheumatoid arthritis: a piggyback study on the pragmatic randomised controlled CareRA trial

“…Despite the fact that several trials and meta-analyses have demonstrated that efficacy outcomes improve when using tumour necrosis factor inhibitor (TNFi) bDMARDs as first-line treatment41 42 they have poor cost-effectiveness profiles 43 44. One of the challenges with these earlier analyses is that prices from before the approval of biosimilar TNFis were used for cost-effectiveness calculations.…”

Long-term efficacy and cost-effectiveness of infliximab as first-line treatment in rheumatoid arthritis: systematic review and meta-analysis

“…While the benefit of immediate infliximab in preventing joint damage has been shown over other treatment strategies [15,34], radiographic progression was out of the scope of this review. Several other recent meta-analyses have compared the combination of biologic agents plus MTX over csDMARDs in early MTX-naïve RA [3, [17][18][19]64] [17] included 20 RCTs in the analysis of ACR20, ACR50 and ACR70 endpoints. In one of the five included infliximab studies, all patients received three months of MTX induction therapy before randomization [17].…”

“…Several other recent meta-analyses have compared the combination of biologic agents plus MTX over csDMARDs in early MTX-naïve RA [3, [17][18][19]64] [17] included 20 RCTs in the analysis of ACR20, ACR50 and ACR70 endpoints. In one of the five included infliximab studies, all patients received three months of MTX induction therapy before randomization [17]. Stevenson et al [64] in a comprehensive HTA report commissioned by NICE, synthesized month 6 ACR and EULAR response outcomes for seven biological drugs, including two infliximab trials.…”

“…Indeed, several bDMARDs, including infliximab and other TNFis, have now been approved for the first-line treatment of patients with severe, active and progressive disease that has not been treated with MTX or other csDMARDs [16]. Recent meta-analyses have demonstrated the short-term benefits of biologic agents over csDMARDs in early, MTX/csDMARD-naïve RA, suggesting that more patients may achieve remission with first-line biological therapy than with csDMARDs [3, [17][18][19]. However, the selection of studies in these meta-analyses were diverse and sometimes incomplete [3, 17,18].…”