Minocycline in the treatment of rheumatoid arthritis : relationship of serum concentrations to efficacy

Objective. To assess the relationships between serum concentrations of minocycline and clinical efficacy and toxicity during the treatment of patients with rheumatoid arthritis (RA) with minocycline. Results. Forty patients with active RA were administered minocycline (maximal oral dose 100 mg twice a day) for 26 weeks. At 3 time points during the treatment, serum samples were collected for measurement of minocycline activity using a microbiological assay. An analysis of variance was performed to estimate an extrapolated concentration at time=0 (C 0 ) for each patient separately and this value of C 0 was regarded to be proportional to the average serum concentration in each patient. The relation between C 0 and clinical response and between C 0 and the occurrence of adverse effects was evaluated. Results. Minocycline was detected in 96 serum samples from 37 patients. Eighty-two percent of the variance in serum concentrations was accounted for by a model incorporating patient, dose, and time effects. A weak correlation between C 0 and clinical response, as expressed by a Ritchie articular index and number of swollen joints, was demonstrated. No correlation was seen between C 0 and toxicity, including gastrointestinal or vestibular adverse effects. Conclusion. Results suggest a relationship between the serum concentrations of minocycline and the clinical response, including Ritchie articular index and number of swollen joints, in the treatment of patients with RA. No relationship was seen between the serum concentrations of minocycline and its toxicity