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AB0456 Combination Leflunomide and Methotreaxate in Refractory RA: A Biologic-Sparing Approach
  1. K.R. Magomero,
  2. B. Hodkinson,
  3. M. Tikly
  1. Department of Medicine, Chris hani Baragwanath academic Hospital, University of the Witwatersrand, Johannesburg, South Africa


Background In resource-constrained settings where biologic agents are not widely available, there are limited therapeutic option for patients with rheumatoid arthritis (RA) refractory to triple disease modifying antirheumatic (DMARD) combination therapy

Objectives To evaluate the efficacy and safety of leflunomide with methotrexate (MTX/LEF) in refractory RA

Methods A retrospective record review of adult RA patients treated with MTX/LEF for ≥4 months at a tertiary hospital in South Africa between 2007 and 2013. Demographic details, adverse reactions, interruptions in therapy and the 3-variable 28 joint disease activity scores (DAS28-3) score were recorded at initiation of LEF/MTX therapy (DAS28-3B), after 4 and 12 months of treatment and at last visit (DAS28-3L).

Results In the 194 predominantly middle-aged female patients with established disease (93% female, mean (SD) age 40.1 (12.2) yrs, disease duration of 12.4 (8.2) and time on previous DMARDs of 7.0 (5.5) yrs. The mean (SD) DAS28-3B was 5.3 (1.0). Following initiation of MTX/LEF, 58.6% of patients achieved a good EULAR response at 4 months, improving to 62.3% by 12 months. In the 172 patients who continued therapy to last visit (a mean (SD) of 2.5 (1.6) yrs), the DAS28-3L had improved significantly to a mean (SD) of 3.6 (1.2), p<0.0001, with 93 patients (54.1%) achieving low disease activity or remission. Therapy was discontinued in 22 patients, for reasons including the wish to fall pregnant, human immunodeficiency virus (HIV) seroconversion, and poor adherence to treatment. Therapy was discontinued in a further 17 (8.8%) patients because of toxicity, and hepatotoxicity (n=3), intolerable gastrointestinal symptoms (n=3), and leucopaenia with septicaemia (n=3) were the most common problems. Two patients died while on LEF therapy and 19 (9.8%) patients were lost to follow up. Treatment was interrupted for more than one month in 153 (89.0%) of patients, most commonly due to inadequate pharmacy supplies of LEF. The significant predictors of a Eular good response to MTX/LEF was a DAS28-3B ≤5.5 (OR=5.1 (95% CI 2.7-9.6), p<0001), and uninterrupted therapy (OR=7.5 (95% CI 2.4-23.8, p=0.0002).

Conclusions The combination of LEF/MTX was effective in the majority of patients who failed other combination synthetic DMARDs, particularly in those with DAS28-B <5.5, and in those without interruptions to this therapy. These results are gratifying despite erratic pharmaceutical supplies of drugs. Fewer than 10% stopped therapy because of adverse effects, and the retention rate was 70%. In a setting where biologic DMARDs are not readily accessible, the combination of LEF/MTX is a cost-effective and relatively safe resource-sparing approach.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.5338

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