Treatment of Early RA with Minocycline - The O'Dell Study

The newest minocycline-RA study by James R. O'Dell, M.D. et al appeared in the May 1997 issue of Arthritis & Rheumatism. Like the studies which preceded it, this study found minocycline a safe and effective treatment for RA. There are some significant differences, however, between this study and other studies of this decade.

The study was placebo-controlled and double-blind, as were the other studies, and also required a 50% improvement in study parameters. NSAIDs were permitted during the trial at a constant dosage; steroids were not allowed.

It was different in that duration of disease was <1 year with a mean patient age of 41 in the minocycline group and 48 in the placebo group. The blinded portion of treatment was 3 months. If no improvement was seen by then, the patient was dropped from the blinded portion. Regardless of response, treatment was stopped in all patients after 6 months. They were then followed in an open portion for 6 months (9 months for the failures at 3 months). If the patient receiving minocycline flared during the open portion, minocycline was restarted. The treating physician was free to use whatever therapy was deemed most appropriate during the open portion.

None of the minocycline patients withdrew because of toxicity, and none reported dizziness that precluded continuation of the protocol.

Of the patients in the minocycline group, 18 out of 23 (65%) had improved by 50% after 3 months and maintained that improvement at the end of the 6 month period, with 5 out of the 18 achieving remission after 1 year. Only 3 out of 23 (13%) placebo patients showed >50% improvement after three months, and only one achieved a remission within the 1 year time frame. Patients in the minocycline group tended to have clinical improvement in all seven efficacy measures: the degree of improvement in morning stiffness, patient global status, physician global status, ESR, total joint score, tender joint score, and swollen joint score. "The within-group changes between baseline and follow-up for all of the efficacy parameters were significant in the minocycline group while the placebo group re-flected no statistically significant changes."

Data from out study and others suggest that maximum benefit of minocycline does not occur until after 1 year of therapy. Therefore, we almost certainly lost patients (27) before they had a maximal response to treatment.

There are various properties of tetracyclines which may play a part in patient response: inhibition of metallo-proteinases, inhibition of tumor necrosis factor, and antibacterial effects. Two currently well-accepted DMARDs, gold and sulfasalazine, were initially used for their antimicrobial properties. Therefore it is clearly possible that an infectious agent will be shown to play a role in the pathogenesis of RA.

We believe our results are even more remarkable because our study design almost certainly decreased the chances of finding a positive effect.

The presently available data on minocycline therapy in RA suggest that such treatment may be considered along with DMARDs such as methotrexate, sulfasalazine, gold salts, and hydroxychloroquine.

FC Breedveld

Be sure to read the editorial by the Hamilton, Ontario group (especially the 1st 2 paragraphs) in the June 1997 J of Rheum on pages 1023-1027, and the following editorial by James O'Dell, M.D. on pages 1028-1030.