title: Pilot clinical trial of intravenous doxycycline versus placebo for rheumatoid arthritis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Institute of Dental and Craniofacial Research, Bethesda, Maryland 20892, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Pillemer
authors.forename: Percio
authors.initials: P
authors.lastname: Gulko
authors.forename: Sophie
authors.initials: S
authors.lastname: Ligier
authors.forename: Cheryl
authors.initials: C
authors.lastname: Yarboro
authors.forename: Mark
authors.initials: M
authors.lastname: Gourley
authors.forename: Raphaela
authors.initials: R
authors.lastname: Goldbach-Mansky
authors.forename: Richard
authors.initials: R
authors.lastname: Siegel
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Hirsch
authors.forename: Frank
authors.initials: F
authors.lastname: Pucino
authors.forename: Barbara
authors.initials: B
authors.lastname: Tilley
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Wilder
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004318:Doxycycline / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D004318:Doxycycline