1152 - Combination Antibiotics as a Treatment for Chronic Chlamydia-Induced Reactive Arthritis

Monday, October 19, 2009: 12:00 PM
Ballroom AB (Pennsylvania Convention Center)
John D. Carter1, Luis R. Espinoza2, R.D. Inman3, K.B. Sneed1, Louis Ricca1, Frank B. Vasey1, Joanne Valeriano1, J.A. Stanich4, C. Oszust4, H.C. Gerard4 and Alan P. Hudson4, 1University of South Florida, Tampa, FL, 2LSU Medical Center, New Orleans, LA, 3Toronto Western Hospital, Toronto, ON, 4Wayne State University, Detroit, MI
Presentation Number: 1152

Purpose:   Chlamydia trachomatis (Ct) and Chlamydophila (Chlamydia) pneumoniae (Cpn) are known triggers of reactive arthritis (ReA).  These chlamydial species exist in a persistent metabolically active infection state in the synovium suggesting that persistent chlamydiae may be susceptible to antimicrobial agents.  The goal of this study was to investigate whether a six-month course of combination antibiotics is an effective therapy for patients with chronic Chlamydia-induced ReA. 
Methods: This study was a 9-month, double-blind, triple-dummy prospective trial assessing a 6-month course of combination antibiotics as a treatment for Chlamydia-induced ReA.  Eligible patients were age 18 to 70 years, fulfilled a modified European Spondyloarthropathy Study Group (ESSG) Criteria, and had disease duration equal to or longer than 6 months.  Subjects had to be polymerase chain reaction (PCR)-positive for Ct or Cpn in order to be randomized to therapy; randomization was performed in a 1:1:1 fashion.  Treatment was for 6 months; the 3 groups included doxycycline 100mg twice daily and rifampin 300mg daily, azithromycin 500mg daily x 5 days then twice weekly and rifampin 300mg daily, or matching placebos.  The primary efficacy endpoint was to assess the number of responders in the combination antibiotic group vs. placebo at month 6 compared to baseline.  Responders were defined as those subjects who improved 20% or more in at least 4 of 6 predefined validated variables without worsening in any one variable. 
Results: 80 subjects were screened and 42 were randomized to treatment (27 to combination antibiotics and 15 to placebo).  Subjects in each group had similar demographics and baseline characteristics.  At month 6, 17/27 subjects (63%) randomized to combination antibiotics were responders compared to 3/15 (20%) on placebo (P-value = 0.01).  Secondary efficacy endpoints showed similar results with significant improvement in the modified swollen joint count, tender joint count, physician global assessment (P-values 0.0007, 0.002, and 0.0009, respectively), and a trend with the erythrocyte sedimentation rate (P-value = 0.07) in those patients on combination antibiotics compared to placebo.  6/27 (22%) subjects on combination antibiotics experienced complete resolution of their symptoms whereas 0/15 subjects on placebo achieved this endpoint.  There were significantly more subjects who became PCR negative at month 6 in the active therapy group than in the placebo group (P-Value = 0.03).  Adverse events (AE’s) were mild; there were no significant differences between the groups.
Conclusion: These data suggest that a 6-month course of combination antibiotics are an effective therapy for chronic Chlamydia-induced ReA and that chlamydial organisms in a persistent infection state are susceptible to this treatment approach.

This study was supported by grant AR-053646 from the US National Institutes of Health.

Keywords: Reiter's syndrome and spondylarthropathy

Disclosure: J. D. Carter, NIH, 2 ; L. R. Espinoza, None; R. D. Inman, None; K. B. Sneed, None; L. Ricca, None; F. B. Vasey, None; J. Valeriano, None; J. A. Stanich, None; C. Oszust, None; H. C. Gerard, None; A. P. Hudson, None.