Background/Purpose:

Best treatment of Rheumatoid Arthritis (RA) requires to begin early, with a tight control, including nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, disease-modifying antirheumatic drugs (DMARDs) and biologic therapies (BT).

High cost limits use of BT, especially in the low-middle income countries. In this setting, a common therapeutic strategy is the use of combination therapy (CT) with methotrexate (MTX) plus leflunomide (LEF). There is not too much information about the efficacy of this CT, and there are some concerns about its safety. Our purpose was to assess the safety of CT in our RA patients.

Methods:

An observational, retrospective study in adult RA patients controlled in our center was conducted. Patients with prescription of MTX plus LEF by June 2016 in pharmacy records were included. We found 253 cases, and randomly 127 were selected for review of clinical records. Five patients with incomplete information were excluded.

Demographic, underlying diseases, time and dose in RA medications, adverse events (AE) and clinical activity data were collected.

Results:

In 121 patients included, 95.9% were females. The mean age was 60.6 (31-86) years. Only 5 of them (4.1%) had pre-existing liver disease, all with fatty liver disease. None of the patients reports alcohol use. Active smoking was reported in 28 cases (23.1%). Continuous use of NSAIDs was documented in 11 patients (9.1%).

Average dose of MTX was 18.6 (7.5-25) mg/wk, with oral route being the most frequent (77.7%). Average dose of LEF was 19.75 (10-20) mg/d, initial loading dose was not used.

In 101 (83.5%) patients CT was retained, with a mean duration therapy of 70.0 (17-162) months. In 20 patients (16.5%) CT was discontinued, with mean time to discontinuation of 49.9 (2-180) months. Kaplan-Meier analysis of survival in CT showed more than 85% of patients still on CT after 5 years.

AE were reported in 31 patients (25.6%), with estimated rate of 4.37 x 100 person-year. Most of them (62.1%) were mild and resolved by reducing doses of one CT drug. AE presented in nine patients lead to a suspension of CT, one of these was considered as serious adverse event (SAE): pulmonary tuberculosis. We didn’t find association between dose of MTX and the risk of adverse effects (p = 0.6).

In the beginning of CT, 90.9% of patients used prednisone, with an average dose of 7.1 mg/d. With CT use, the average dose was significantly reduced to 4.9 mg/d (p <0.0001).

In 7 cases (5.8%) a BT was initiated because of the persistent high clinical activity RA. All of them suspended CT, continuing with only MTX or LEF.

In 60 of 101 patients remaining on CT, clinical activity of RA was registered by DAS 28 during follow-up. In 50% of them remission or low activity was achieved.

Conclusion:

In this group of Chilean RA patients, the MTX plus LEF CT show to be safe, with a good survival rate.

AE were observed in the 25% of the patients on CT, and most of them resolved with the reduction of the dose of MTX or LEF. Frequency of SAE was very low.

A half of the patients who remained on CT, and evaluated with DAS 28 during follow up achieved remission or low RA activity, with a significant steroid-sparing effect.

CT is a reasonable therapeutic alternative when there is a limited access to the BT.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/safety-of-methotrexate-and-leflunomide-combination-therapy-in-the-treatment-of-rheumatoid-arthritis/