Background/Purpose:  In patients with rheumatoid arthritis (RA), in whom methotrexate (MTX) is not inducing remission or at least low disease activity, or is not tolerated, leflunomide is one conventional synthetic DMARD option that is still commonly used in some countries. We thus investigated whether real life patients with RA benefit from instituting leflunomide after methotrexate.

Methods:   The clinical data of all RA patients who had at least once received leflunomide, and who agreed to the pseudonymized analysis of their data (approved by the local ethics committee), were analyzed from the time of leflunomide initiation on to the time of stopping leflunomide or the last visit in 2015, which ever came first.

Results:   144 RA patients treated with leflunomide were identified. Of these, 86 received leflunomide after MTX had failed as a first line DMARD, and 8 received leflunomide as a first line DMARD. 50 patients had another first line therapy. Of the first line leflunomide patients 3 (38%) were still on leflunomide at the last visit, as compared to 6 of the 43 patients (14%) who were switched from MTX to leflunomide, and 0 of the 27 patients in whom leflunomide was added to MTX (p<0.01 vs 1^st line leflunomide). For leflunomide monotherapy, 29% and 19% were still on the drug after 24 and 48 months, respectively, as compared to 14 and 0% under the combination with MTX. Of all patients who started leflunomide, remission (at least low disease activity) as per CDAI (≤2.8 (≤10)) was reached by 23% (57%) 3 months, 20% (40%) 6 months, and 16% (34%) one year after initiating leflunomide monotherapy, with corresponding percentages of patients of 39% switched to other approaches at six months and of 60% switched at one year. Under the combination of leflunomide and MTX, remission (at least low disease activity) was seen in 18% (53%) at 3 months, 20% (37%) at 6 months, and 8% (20%) at one year, and 55% and 71% had switched to other modes of action at six months and one year, respectively. Gastrointestinal and mucocutaneous adverse events and hypertension were common, and 4 our patients experienced serious bacterial infections.

Conclusion:   While leflunomide may be a longer term option for a subgroup of RA patients with contraindications to MTX or after MTX failure, only a third of patients had acceptable disease control after one year under leflunomide monotherapy, and one in five under leflunomide combined with MTX. These results are supportive of the EULAR recommendations that patients should be switched to a second conventional DMARD in the absence of predictors of bad outcome only. If leflunomide is initiated, the patients need to be followed closely for potential secondary loss of efficacy. 

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/in-real-life-rheumatoid-arthritis-patients-leflunomide-has-limited-impact-as-a-second-line-dmard-after-methotrexate/