Leflunomide monotherapy versus combination therapy with conventional synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis: a retrospective study

Abstract

Leflunomide (LEF) is a conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of rheumatoid arthritis. However, there are few reports on the comparison of efficacy between LEF alone and combined with other csDMARDs. Here, the efficacy and safety of LEF monotherapy (88) and combination (361) therapy groups were evaluated. After 3 months, there were no significant differences in 28-joint disease activity score (DAS28), health assessment questionnaire (HAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) between the monotherapy and combination groups (all P > 0.05). According to the European League Against Rheumatism (EULAR) response criteria, it was found that the DAS28 response rates were similar in the two groups (P > 0.05). Besides, the two groups presented similar safety profiles. Subgroup analysis found that there was no difference in efficacy among the three combined therapies (LEF + methotrexate (MTX), LEF + hydroxychloroquine (HCQ), and LEF + MTX + HCQ) and LEF monotherapy. Furthermore, when the dose of LEF was less than 40 mg/day, no significant difference in efficacy was observed between low and high doses. Overall, these results indicated that low dose LEF monotherapy was not inferior to the combination therapy. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovitis, and its primary clinical manifestations is symmetric arthritis affecting multiple joints. Inflammation and joint erosion cause physical function disorder, which severely reduces the quality of life. The global prevalence of RA is 0.5-1% 1,2 , the incidence of RA among females is 2 to 3 times than of males, and the incidence in females shows an increasing trend 3,4. Although multiple studies have reported that the occurrence of RA is related to environmental, hormonal and genetic factors 5-7 , the specific pathogenesis of RA remains unclear, which is difficult to achieve radical cure. The main goal of treating RA at present is to control and alleviate the disease. Currently, drugs for treating RA mainly include conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), targeted synthetic DMARDs (tsDMARDs), biological DMARDs (bDMARDs), biosimilar DMARDs (bsDMARDs), and glucocorticoids (GCs) 8. Economical and effective csDMARDs are the first treatment strategy recommended by the European League Against Rheumatism (EULAR) 8 , including leflunomide (LEF), methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SSZ), cyclosporine, azathioprine and gold salts. Among them, LEF was approved by the Food and Drug Administration for the treatment of RA in 1998 and plays a role in controlling and relieving the condition of the disease through acting on dihydroorotate

In-silico Prediction of Maximum Binding Affinity of Disease-Modifying Antirheumatic Drugs with Homo sapiens Acrosomal Protein SP-10

“…RA is a chronic and highly destructive autoimmune disease characterized by symmetrical joint pain and swelling [13,14]. Recent findings stated that DMARDs such as Hydroxychloroquine, Leflunomide, Methotrexate, Tofacitinib, Baricitinib, and Upadacitinib used in RA treatment also showed drastic effects on fertility [15][16][17][18][19][20][21][22][23][24][25][26][27]. However, a few clinical reviews and case studies support the side effects of DMARDs, and the interactions of these medicines with fertility-related biomolecules are not clearly understood.…”

Effect of Er Miao San on rheumatoid arthritis via the NF-κB signaling pathway: Based on network pharmacology and experimental validation

“…At present, the overall purpose of treatment for RA is to alleviate or signi cantly reduce the activity of the disease to prevent joint injury or disability 9 . Disease-modifying antirheumatic drugs (DMARDs) can be suppressed in patients with RA overactive immune function and in ammation, but the use of these drugs may result in a variety of adverse effects 10,11 . Given this, it is essential to explore drugs for the treatment of RA.…”

Comparative efficacy and safety of JAK inhibitors and leflunomide in rheumatoid arthritis: A protocol for systematic review and meta-analysis

“…Leflunomide (LEF) is one of the most commonly used disease-modifying anti-rheumatic drugs (DMARDs) for the treatment of RA in clinical practice, [ 7 – 8 ] and it was listed as one of the top three recommended treatments for rheumatoid arthritis by the American College of Rheumatology in 2008[9]. Because its early use can significantly improve the prognosis of patients with RA, LEF has been effectively used for early RA and has been shown to significantly inhibit disease as assessed progression by joint imaging.…”