Safety and efficacy of hydroxychloroquine as maintenance therapy for rheumatoid arthritis after combination therapy with methotrexate and hydroxychloroquine.

OBJECTIVE: To evaluate the ability of hydroxychloroquine sulfate (HCQ) to extend the response to combination therapy with HCQ and methotrexate (MTX) and the safety of longterm HCQ maintenance therapy in patients with active rheumatoid arthritis (RA). METHODS: Two-part study consisting of an open label segment evaluating combination HCQ/MTX therapy followed by a double blind segment evaluating maintenance therapy for a total of 60 weeks. First, all patients were treated with HCQ 400 mg/day and MTX 7.5 to 15 mg/week for 24 weeks. Then, responders were randomized into 3 groups: (1) HCQ with MTX as needed for disease flare (n = 40), (2) HCQ 400 mg/day (n = 41), or (3) placebo with MTX as needed for disease flare (n = 40), each for 36 weeks. RESULTS: Clinical disease and laboratory variables improved significantly during initial combination therapy with HCQ and MTX. After MTX withdrawal, HCQ-containing maintenance regimens delayed the onset of disease flare (p = 0.023). There were no unexpected adverse events at any time or between-group differences in the distribution of adverse events during the double blind segment. CONCLUSION: Combination of HCQ and MTX appeared to be effective and well tolerated for 24 weeks. After withdrawal of MTX, HCQ extended the response seen with combination therapy and was well tolerated for 36 weeks. Initial therapy with HCQ and MTX, followed by maintenance HCQ, may be a useful alternative for the treatment of RA.

Light and electron microscopic studies on the synovial membrane in Reiter's syndrome. Immunocytochemical identification of chlamydial antigen in patients with early disease.

Studies by light microscopy on synovium obtained from 11 patients with Reiter's syndrome during the first month of an episode showed proliferation of synovial lining cells, polymorphonuclear neutrophils among the synovial lining cells, increased surface fibrin, and vascular congestion. Biopsy specimens taken later showed vascular congestion and still proliferated synovial lining cells, fewer polymorphonuclear neutrophils in some, and a tendency toward increased infiltration with lymphocytes and plasma cells. Electron microscopy of samples from 8 patients during the first month of disease activity showed occlusion of vessels by platelets in 4, and fibrin or dense granular material in the vessel walls in 4. Five of the patients with arthritis of less than 4 weeks duration had unidentified intracellular and extracellular particles; some of these were highly suggestive of Chlamydia. No such particles were noted in samples from patients with more chronic cases. Using an antibody to Chlamydia trachomatis and the peroxidase-antiperoxidase technique, immunocytochemistry showed reaction product in synovial macrophages in 2 patients with arthritis of less than 4 weeks duration, but not in the 1 patient studied who had more chronic disease. These studies provide support for dramatic synovial vascular injury consistent with that caused by endotoxin and the presence of chlamydial antigen in synovial macrophages, at least in the early phases of synovitis.