Minocycline and doxycycline therapy in community patients with rheumatoid arthritis: Prescribing patterns, patient-level determinants of use, and patient-reported side effects

Introduction: Minocycline and doxycycline are safe and moderately effective disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of early, DMARD-naïve rheumatoid arthritis (RA), although little is known about their use outside clinical trials. We characterize the use of minocycline and doxycycline in community-dwelling RA patients by examining associated prescribing patterns, patient-level determinants of use, and side-effect profiles. Methods: We studied 15,716 patients with RA observed between 1998 and 2009 while participating in a long-term US observational study. Results: Minocycline or doxycycline was prescribed by 18% of rheumatologists (interquartile range one to two patients per physician) to 9% of RA patients. Significant differences between minocycline-treated and doxycyclinetreated patients and nontreated patients included age (58.4 years vs. 59.8 years), RA duration (14.8 years vs. 13.7 years), Caucasian race (93.7% vs. 89.7%), lifetime DMARDs and biologics (3.3 vs. 2.5), prednisone use (40.1% vs. 35.3%), and Medical Outcomes Study 36-Item Short Form Survey physical component summary score (35.0 vs. 36.4). In multivariable Cox regression, patients initiating minocycline or doxycycline had increased disease activity, more comorbidities, and a greater number of prior nonbiologic DMARDs. Side effects were reported by 17.8% of minocycline users and 11.8% of doxycycline users. Skin complaints accounted for 54% of minocycline patientreported side effects. The most commonly effected organ systems for doxycycline were gastrointestinal (35.4%) and skin (33.7%). Approximately 75% of side effects were of mild or moderate severity. Conclusions: Rheumatologists have not embraced minocycline or doxycycline as primary treatment options for RA and reserve their use primarily in patients with long-standing, refractory disease. These drugs are generally well tolerated, with skin complaints, nausea, and dizziness being the most common patient-reported side effects.