Pilot Clinical Trial of Intravenous Doxycycline Versus Placebo for Rheumatoid Arthritis

STANLEY PILLEMER, PERCIO GULKO, SOPHIE LIGIER, CHERYL YARBORO, MARK GOURLEY, RAPHAELA GOLDBACH-MANSKY, RICHARD SIEGEL, ROSEMARIE HIRSCH, FRANK PUCINO, BARBARA TILLEY, and RONALD L. WILDER

ABSTRACT.

Objective. To screen for potential efficacy and assess the feasibility of intravenous (IV) doxycycline as a treatment for rheumatoid arthritis (RA).

Methods. The study was a (stratified, block) randomized, double blind, 12 week, pilot trial of IV doxycycline 300 mg/day versus identical appearing IV placebo given over 2 h for 14 days. The primary comparison was to a hypothesized placebo rate of 20% as described by Paulus. If a total of 14 consecutive subjects receiving doxycycline treatment did not respond, it would be considered futile to proceed to a Phase III trial. We planned a placebo group of 14 subjects to verify the placebo response rate and estimate sample size required for a definitive Phase III trial, if such a trial was warranted based on the pilot study. American College of Rheumatology (ACR) RA response criteria were used. After 23 subjects entered, the study was closed due to recruitment difficulties.

Results. At baseline, mean (SD) tender joint count was 37 (11.9), swollen joint count 30 (9.6), morning stiffness 317 (319) min, and erythrocyte sedimentation rate 72 mm/h (27.5). Randomization resulted in 10 subjects receiving doxycycline and 13 receiving placebo. Treatment was stopped in 8 subjects: in 6, treatment was ineffective (one taking doxycycline, 5 placebo), and in 2, rashes occurred (one taking doxycycline, one placebo). Only one subject met ACR response criteria in the doxycycline group and none in the placebo group. Having no responders in the placebo group was consistent with placebo response rate of 20% or less. Several patients required peripherally inserted central catheters for venous access.

Conclusion. The efficacy of IV doxycycline as a treatment for RA could not be ruled out. However, as the proportion of responders was small, it is unlikely that potential efficacy of IV doxycycline would outweigh potential disadvantages of IV administration. (J Rheumatol 2003;30:41-3)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
DOXYCYCLINE
CLINICAL TRIAL

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From the National Institute of Dental and Craniofacial Research, the National Institute of Arthritis, Musculoskeletal and Skin Diseases, the Clinical Center, and the National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; the North Shore-Long Island Jewish Research Institute, Manhasset, New York; Washington Hospital Center, Washington, DC; and the Division of Biometry and Epidemiology, Institution, Medical University of South Carolina, Charleston, South Carolina, USA.

S. Pillemer, MD, National Institutes of Dental and Craniofacial Research; P.S. Gulko, MD, North Shore-Long Island Jewish Research Institute; S. Ligier, MD, National Institute of Mental Health; C. Yarboro, RN; R. Goldbach-Mansky, MD; R. Siegel, MD, National Institutes of Arthritis, Musculoskeletal and Skin Diseases; M. Gourley, MD, Washington Hospital Center; F. Pucino, PharmD, Clinical Center; B. Tilley, PhD, Medical University of South Carolina; R.L. Wilder, MD, PhD, MedImmune, Gaithersburg, MD.

Address reprint requests to Dr. S.R. Pillemer, Gene Therapy and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 10 Center Drive, Room 1N113, MSC 1190, Bethesda, MD 20892, USA.

Submitted April 3, 2002; revision accepted July 2, 2002.

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