Background/Purpose:  There is a high risk of developing adverse drug reactions (ADR) in rheumatology due, mainly, to the Disease Modifying Drugs (DMARD) used. After more than twenty years using DMARD, is widely known their efficacy in rheumatoid arthritis (RA), but it is necessary to increase our knowledge of its ADR, especially those that lead to discontinuation in real life. The purpuse of our study was to describe the incidence rate and characteristics of moderate and severe ADR to DMARD in patients with RA.

Methods:  Observational longitudinal study was conducted. Recent onset RA patients diagnosed between April 15^th 2007 and 31^st December 2010 followed in outpatient clinic at Hospital Clinico San Carlos until December 31^st2015, which used any DMARD treatment were included. Primary outcome: development of an ADR that required discontinuation of the DMARD (moderate: discontinuation of the drug; severe: discontinuation and hospitalization or death as a result of the ADR). Incidence rates of discontinuation (IR) per 100 patient-years were estimated using survival techniques with their respective 95% confidence interval [CI].

Results:  We included 293 courses of DMARD treatment in 97 patients (815 patient-years). Of these, 78% were women with a mean age at diagnosis of 55.6 ± 15 years. The median time to the start of the first DMARD was 0[0-41] days. 11.5% were taking biological DMARDs, 60.75% were using combined therapy and 86% were taking corticoids. Treatment was suspended due to ADRs in 110 cases (IR: 13.5 [11.2 -16.3]), being gastrointestinal the most frequent cause (21.4%), followed by infections (15.2%). The IR of moderate ADR was 11.2[9.2-13.8], being 11.1[8-15] for monotherapy regimen and 11.4 [8.8-14.9] for combined therapy. The IR of discontinuation related to synthetic and biological DMARDs was 13.2 [0.9-16.2] and 15.6 [8.6-28.2] respectively. The crude IR of discontinuation for moderate ADRs was higher for Gold (IR: 19.5[11.5-32.9]) and Leflunomide (IR: 20.5[10.7-39.5]) being 7.14 [4.8-10.4] for Methotrexate (MTX). 17.5% of the ADR were severe (n=20) with an IR of 2.5[1.6-3.8] being infections the most frequent cause (65%) followed by cancer (20%), gastrointestinal (10%) and exitus (n=1). The crude IR of discontinuation for severe ADRs was higher for biological DMARDs (IR: 4.2[1.3-13.2]) than for synthetic DMARDs (2.28 [1.4-3.6]). The crude IR of discontinuation for severe ADRs was the lowest for Antimalarials (IR: 1.5[0.5-4.8]) and MTX (IR: 1.3[0.5-3.1]. Regarding types of regimen, the IR of severe ADR on monotherapy was 1.5 [0.6-3.5], and with combined therapy was 3.1[1.8-5.1], being higher when we looked at triple therapy (IR: 4.5 [2.4-8.3]).

Conclusion: This study describes the incidence of ADRs occurred in RA patients taking DMARDs in real life conditions. The IR of ADR estimated was 13.5% patient-years, being 2.5% patient-years for severe ones. MTX was the drug with the lowest IR of ADRs. Regarding severe ADRs caution might be taken for those patients on triple therapy.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/adverse-drug-reactions-due-to-disease-modifying-drugs-in-patients-with-rheumatoid-arthritis/