Background/Purpose: In rheumatology, we are aware of the possibility to develop adverse drug reactions (ADR) to the widely used Disease Modifying Drugs (DMARD). We are certain of the efficacy of the DMARD in the treatment of rheumatoid arthritis (RA) and we know their safety profile in clinical trials. However, it is necessary to increase our knowledge of their ADR, especially those that lead to discontinuation, in real life conditions. Purpose: to describe the incidence and characteristics of moderate ADR (MADR) to DMARD in patients with incident RA as well as the factors related to their development.

Methods: Observational longitudinal study. Patients: all recent onset RA diagnosed between April 15^th 2007 and December 31^st 2014 followed in outpatient clinic at Hospital Clínico San Carlos until December 31^st 2016, which used any DMARD (synthetic and biologic). Primary outcome: development of a MADR (discontinuation of the DMARD due to the ADR). Incidence rates of discontinuation (IR) per 100 patient-years were estimated using survival techniques with their respective 95% confidence interval [CI]. Comparisons between associated factors were run by Cox bivariate and multivariate regression models. Results were expressed by hazard ratio (HR) and [CI].

Results:

We included 2388 courses of DMARD treatment in 814 patients (3706.14 patient-years). 77.52% were women with a mean age at diagnosis of 57.53±15.50 years. From the courses of DMARD, 13.74% were biologicals (72.04% anti-TNF) and 60% were used in monotherapy. There were 591 ADR in 335 patients, 90.52% of them moderate. Gastrointestinal was the most frequent cause of MADR (31.96%), followed by hepatic (10.15%). IR are shown in table 1. We performed a multivariate analysis (table 2) adjusted by ESR at the beginning of each drug. We repeated the model changing the reference category of DMARD: Golimumab (HR: 2.21, p=0.010), Leflunomide (HR: 1.84, p=0.000), Sulfasalazine (HR: 1.47, p=0.012), Chloroquine (HR: 1.37, p=0.004) and Hidroxichloroquine (HR: 0.77, p=0.030); the rest of DMARD did not achieve statistical significance in the models performed.

Conclusion: The IR of MADR estimated was 14.4%, being gastrointestinal the main cause. We found differences in discontinuation rates among DMARD due to MADR, with Golimumab, Leflunomide, Sulfasalazine and Chloroquine being the drugs with the highest risk. Methotrexate and Hidroxichloroquine are a protective factor for the development of MADR. Caution should be taken in patients of female gender, with positive rheumatoid factor, receiving combined therapy, higher dose of corticoids and with certain comorbidities.

« Back to 2018 ACR/ARHP Annual Meeting

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