Background: Currently, conventional synthetic DMARDs (csDMARDs) are the most commonly prescribed drugs as first-line treatment for peripheral arthritis. In resource-constrained settings where biologic agents are not widely available, there are limited therapeutic options for patients with rheumatoid arthritis (RA) and seronegative inflammatory arthropathies refractory to other csDMARD therapies. Hence, in our practice, we are inclined to use combination of potent DMARDs after MTX failure, prior to considering biologic therapies. We believe that combination of DMARDs, especially combining MTX and Leflunomide (LEF) provides a potent and valuable low-cost treatment option. Efficacy of MTX and LEF is very well established, but there have been lot of concern as regards their combination use due to potential risk of hepatotoxicity.

Objectives: We aimed to review our inflammatory arthropathies cohort data especially examining the safety, efficacy and drug retention of the combination usage of MTX and Leflunomide. We addressed this question using real-world data from the PRIME registry.

Methods: This was a cross-sectional study conducted using data collected at the time of patient enrolment in the PRIME registry. The PRIME Registry is a large, independent, prospective, observational cohort initiated in October 2019 that comprises patients diagnosed with RA, SLE, PsA or AS by a rheumatologist, and is being actively followed up. IRB approval and informed consent was obtained. A number of clinical variables were recorded. Detailed history was gathered from every patient regarding their present and past medications usage. Questions were asked directly about the usage or otherwise of all available DMARDs and biologics. The duration of usage, any adverse events, or the reasons for discontinuation were recorded. Evaluation of disease activity and severity was made as per internationally agreed definitions.

Results: The data of 766 inflammatory arthritis patients (RA=663, PsA=103) was reviewed. Among them, 241 patients (RA=196, PsA=45) were using combination therapy of MTX and LEF (combo MTX+LEF) with mean age 42.3±6 years; 42% male]. These patients had failed MTX or LEF monotherapy. Among these 241 patients, 49 patients were also on concomitant hydroxychloroquine therapy. It was noted that median drug retention of combo MTX+LEF therapy has been 9.5 months (IQR 6-16). Regarding any adverse events of combo MTX+LEF therapy, hepatotoxicity (ALT ≤3 times the upper limit of normal) was noted among 15 (6.2%) patients, hepatotoxicity (ALT ≥3 times the upper limit of normal) was noted among 8 (3.3%) patients, and troublesome gastrointestinal upset (nausea, or vomiting, or diarrhoea) in 3 (1.2%). Overall, only 13 (5.4%) patients had to discontinue this combo MTX+LEF therapy due to adverse events. Disease activity among combo MTX+LEF users was as follows: 64% (n=29) of PsA patients had achieved MDA; 42% (n=83) of RA cohort were in DAS28 remission, 46% (n=91) of RA patients were having DAS low disease activity.

Conclusion: Combination of MTX and LEF was well tolerated and had good drug retention time, with 94.6% of patients having ongoing treatment to date. In low-income countries, where bDMARD availability is limited, financial arguments significantly influence decision making process, and our data provides initial evidence that MTX and LEF combination therapy could be an effective treatment option.

Disclosure of Interests: Muhammad Haroon Speakers bureau: Roche, Novartis, Grant/research support from: Abbvie, Pfizer, Arfa Ashraf: None declared, Hafiza Javeria Shaheen: None declared, Sadia Asif: None declared, Shabnam Batool: None declared, Farzana Hashmi: None declared, Saadat Ullah: None declared