Doxycycline versus Doxycycline and Rifampin in Undifferentiated Spondyloarthropathy, with Special Reference to Chlamydia-Induced Arthritis. A Prospective, Randomized 9-Month Comparison

JOHN D. CARTER, JOANNE VALERIANO, and FRANK B. VASEY

ABSTRACT.

Objective. Chlamydia is a known trigger of reactive arthritis (ReA). It may also be common cause of undifferentiated spondyloarthropathy (uSpA). Persistent, metabolically active, Chlamydiae have been observed in the synovial tissue of these patients years after their initial exposure. Trials with lymecycline and rifampin have shown benefit in early/acute Chlamydia-induced arthritis. In vitro data suggest that persistent Chlamydia become resistant to chronic monotherapy of tetracyclines or rifampin, whereas no such resistance is noted when rifampin is added to antimicrobials that are active against Chlamydia. Rifampin and doxycycline also show synergistic effect against Chlamydia. In addition, rifampin inhibits chlamydial production of heat shock proteins (HSP). HSP60 plays a key role in the chronic persistent state of Chlamydia. We conducted a prospective, randomized 9-month trial to evaluate the efficacy of doxycycline versus a combination of doxycycline and rifampin in the treatment of uSpA.

Methods. The study enrolled 30 patients with chronic inflammatory arthritis (average disease duration 10 yrs) who fulfilled the European Spondylarthropathy Study Group criteria, with no evidence of inflammatory bowel disease, psoriasis, ankylosing spondylitis, or preceding dysentery. Patients received doxycycline 100 mg po twice daily or a combination of doxycycline 100 mg po twice daily and rifampin 600 mg po daily. They received a 4-question self-questionnaire and a blinded joint examination at each visit. The questions include a visual analog scale (VAS) for their current amount of back pain, duration of morning stiffness, back pain at night, and peripheral joint pain. The blinded joint examination consisted of a swollen joint count (SJC) and a tender joint count (TJC). These 6 variables were assessed at baseline and at 1, 3, 6, and 9 months. Responders were defined as those who improved ≥ 20% in at least 4 of the 6 variables at 9 months of therapy.

Results. Comparing the doxycycline + rifampin arm (D/R) versus the doxycycline arm (D) at 9 months of therapy, all 6 variables improved more in D/R versus D, 4 of which were statistically significant. The mean VAS (scale of 100) decreased 24.4 points in D/R in contrast to 3 points in D (p < 0.03). Duration of morning stiffness decreased by 1.2 h in D/R, with a slight increase of 0.1 h in D (p < 0.003). The back pain at night and peripheral joint pain both improved in D/R group versus D (not statistically significant). Finally, the SJC and TJC also improved in D/R (–2.1 and –2.5) versus D (–0.4 and –0.6; p = 0.02, p = 0.03, respectively). Eleven of 15 patients in the D/R arm were responders, whereas only 2 of 15 D group patients were considered responders (p < 0.003).

Conclusion. The combination of doxycycline and rifampin for 9 months seemed to be effective in treatment of chronic uSpA. This is the first study to demonstrate therapeutic benefit with antimicrobials to a chronic inflammatory arthritis possibly secondary to persistent Chlamydia. (J Rheumatol 2004;31:1973-80)

Key Indexing Terms:

REACTIVE ARTHRITIS
SPONDYLOARTHROPATHY
CHLAMYDIA
DOXYCYCLINE
RIFAMPIN
HEAT SHOCK PROTEIN

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From the Division of Rheumatology, University of South Florida, Tampa, Florida, USA.

J.D. Carter, MD, Assistant Professor of Medicine; J. Valeriano, MD, Associate Professor of Medicine; F.B. Vasey, MD, Professor of Medicine, Division of Rheumatology.

Address reprint requests to Dr. J.D. Carter, Division of Rheumatology, University of South Florida, 12901 Bruce B. Downs Blvd., MDC 81, Tampa, FL 33612. E-mail: jocarter@hsc.usf.edu

Submitted December 19, 2003; revision accepted April 19, 2004.

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