Network Meta-Analysis Validates the Use of Methotrexate in RA Compared With Other Treatments

Results from a meta-analysis reinforced the use of methotrexate as the primary reference conventional synthetic disease-modifying antirheumatic drug (csDMARD) in the treatment of rheumatoid arthritis (RA), according to a recent study published in JAMA Network Open.

Meta-analysis concept | Image credit: Planet Studio - stock.adobe.com

Treatment approaches in RA have made significant advances in the last century since the use of gold and glucocorticoids (GC) were introduced in 1932 and 1942, respectively. Since 2000 in particular, the use of csDMARDs, targeted DMARDs (tDMARDS), biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) have become more common.

As the treatment paradigm has shifted in RA, the authors of the present study point to a network meta-analysis (NMA) conducted in 2020. This analysis included over 35 NMAs conducted on outcomes related to tDMARDs; however, no NMAs were conducted on csDMARDs despite 70% of patients with RA receiving these drugs as a part of their treatment plan. A more holistic understanding of the impacts of various RA medications could be useful considering evidence suggests the combination of multiple csDMARDs is similarly effective to tDMARDs. To expand on the knowledge surrounding treatment outcomes in RA, researchers conducted a NMA on randomized control trials (RCTs) to investigate outcomes related to the use of multiple csDMARDs and GC.

They included RCTs that assigned patients with RA to either a placebo, GC, csDMARD, or a pharmacologic non–disease-modifying comparator with at least 1 reported outcome on tender joint count (TJC), swollen joint count (SWJ), erythrocyte sedimentation rate (ESR), or C-reactive protein (CRP) levels. Data and articles were gathered through searches in MEDLINE, ClincialTrials.gov, Cochrane Central, and Embase.

A total of 13,260 patients with RA were identified throughout 132 RTCs, which included 29 interventions among 275 treatment groups. On average, patients in these studies were 53 years of age and 71% of patients were female. Furthermore, patients experienced a mean duration of RA of 79 months and had average activity scores of 6.3 (measured according to the 28-joint Disease Activity Scale [DAS28]). Additionally, average baseline ESR, SJC, TJC, and rates of rheumatoid factor (RF) positivity registered at 51.6 mm/h, 15.8 joints, 18.6 joints, and 77%.

In the NMA, methotrexate was the most thoroughly evaluated csDMARD that demonstrated the most reliable treatment outcomes. Oral methotrexate, compared with placebos, was linked to an overall reduction in TJC by 5.18 joints. Glucocorticoids, among the other drugs assessed, were linked to similar or lower reports of TJC (–2.54 joints) compared with methotrexate; however, cyclophosphamide demonstrated slightly higher TJC benefits (improvement of 6.08 joints). Methotrexate was noted as favorable compared with sulfasalazine, D-penicillamine, chloroquine, peroral gold, levamisole, azathioprine, and GC.

Among the limitations mentioned in this study, the authors addressed potential bias that can exist these studies, insufficient reporting, and the fact that they did not make any comparisons to antibiotic treatments. However, despite these hinderances, they have a strong belief in the strength of the studies they analyzed. Their results did not justify the reintroduction of previously used drugs such as levamisole, azathioprine, gold, D-penicillamine, or cyclophosphamide, but their findings further validated the use of methotrexate as the primary reference csDMARD in the treatment of RA.

Reference

Guski LS, Jürgens G, Pedder H, et al. Monotreatment with conventional antirheumatic drugs or glucocorticoids in rheumatoid arthritis: a network meta-analysis. JAMA Netw Open. 2023 Oct 2;6(10):e2335950. doi:10.1001/jamanetworkopen.2023.35950