• number of responders in the combination antimicrobial groups versus number of responders in the placebo group (measured at Month 6)
• "responder" defined as 20% or more improvement in at least 4 of 6 criteria: 1) swollen joint count, 2) tender joint count, 3) morning stiffness duration (low back), 4) current low back pain, 5) current peripheral joint pain, 6) patient global assessment

• Individual comparison of 6 "responder" criteria in the combination antimicrobial groups versus the placebo group [ Time Frame: Months 6 and 9 ] [ Designated as safety issue: No ]
• Comparison of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) [ Time Frame: Month 6 ] [ Designated as safety issue: No ]
• Psoriatic Arthritis Response Criteria (PsARC): swollen joint count, tender joint count, physician and patient global assessment [ Time Frame: Months 6 and 9 ] [ Designated as safety issue: No ]
• Disease Activity Score 44 (DAS44): Ritchie Articular Index (tender joint count), swollen joint count (out of 44 joints), ESR, patient global assessment (visual analog scale) [ Time Frame: Months 6 and 9 ] [ Designated as safety issue: No ]
• Dactylitis [ Time Frame: Months 6 and 9 ] [ Designated as safety issue: No ]
• Enthesitis (presence or absence of plantar fasciitis or Achilles tendonitis) [ Time Frame: Months 6 and 9 ] [ Designated as safety issue: No ]
• Health Assessment Questionnaire (HAQ) [ Time Frame: Months 6 and 9 ] [ Designated as safety issue: No ]
• Number of patients with a complete response (resolution of all symptoms) [ Time Frame: Months 1, 3, 6 and 9 ] [ Designated as safety issue: No ]

• individual comparison of above 6 criteria in the combination antimicrobial groups versus the placebo group
• comparison of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
• Psoriatic Arthritis Response Criteria (PsARC): swollen joint count, tender joint count, physician and patient global assessment
• Disease Activity Score 44 (DAS44): Ritchie Articular Index (tender joint count), swollen joint count (out of 44 joints), ESR, patient global assessment (visual analog scale)
• dactylitis
• enthesitis (presence or absence of plantar fasciitis or Achilles tendonitis)
• Health Assessment Questionnaire (HAQ)
• number of patients with a complete response (resolution of all symptoms) (all measured at Months 1, 3, 6, and 9)

Reactive arthritis, also known as Reiter's syndrome, is a form of arthritis that occurs as a reaction to an infection elsewhere in the body. It is characterized by inflammation of the joints, tendons, urogenital tract, and eyes. Pain and swelling in the knees, ankles, and feet are common. This study will determine the effectiveness of antibiotic therapy in treating people with chlamydia-induced reactive arthritis that has lasted for more than 6 months.

The initial infection that causes reactive arthritis is caused by one of two bacteria: Chlamydia trachomatis, which is usually acquired through sexual contact, or Chlamydia pneumoniae, which can cause respiratory infections. Most people recover fully from the initial flare of arthritis symptoms. However, about 20% of people with reactive arthritis experience long-lasting symptoms. In these individuals, the Chlamydia bacteria exist in a persistent metabolically active state within the joint tissue, even years after the initial exposure. The bacteria produce heat shock proteins (HSPs), which are thought to play a key role in the chronic persistent state of Chlamydia and which may stimulate the immune inflammatory response seen in reactive arthritis. This indicates the need for antimicrobial therapy that can reduce Chlamydia's HSP production and block its metabolism. The purpose of this study is to determine the effectiveness of long-term combination antibiotic therapy in treating people with chronic reactive arthritis. The study will use two different combinations of common antibiotics: doxycycline paired with rifampin and azithromycin paired with rifampin.

This study will entail 6 months of treatment followed by 3 months of follow-up. After screening, eligible participants will be randomly assigned to one of three treatment groups: rifampin once a day plus doxycycline twice a day; rifampin once a day plus azithromycin once a day for 5 days, then twice weekly; or placebo. Study visits will occur at baseline and Months 1, 3, 6, and 9. At all visits, participants will undergo an interview, a physical examination, and blood collection. They will also complete a questionnaire related to their symptoms and functional status. At screening and Month 6, a synovial biopsy may be performed. This will involve taking a sample of the tissue that lines the joints.

• Arthritis, Reactive
• Reiter Disease

• Drug: Doxycycline and Rifampin
• Drug: Azithromycin and Rifampin
• Drug: Placebo

• Active Comparator: Participants will receive Azithromycin and Rifampin
• Active Comparator: Participants will receive Doxycycline and Rifampin
• Placebo Comparator: Participants will receive placebo

Inclusion Criteria:

• Meet the following European Spondyloarthropathy Study Group Criteria:

  1. inflammatory spinal pain OR
  2. synovitis AND

  3. one or more of the following:

     1. positive family history
     2. urethritis or cervicitis within 1 month prior to onset of arthritis
     3. buttock pain
     4. enthesopathy
     5. sacroiliitis
• Disease duration of at least 6 months
• Negative pregnancy test at study baseline and willing to use an effective method of contraception other than combined oral contraceptives for the duration of the study (for women of childbearing age)

Exclusion Criteria:

• Sensitivity or history of allergic reaction to rifampin, doxycycline, or azithromycin
• Currently taking any medications that may interact with the study medications, specifically rifampin
• Liver transaminases greater than or equal to two times the normal level
• Significant abnormalities in the complete blood count (CBC)
• Pregnant
• Current psoriasis
• Diagnosis of inflammatory bowel disease
• Diagnosis of ankylosing spondylitis
• Previous prolonged exposure to antibiotics (more than 2 weeks) as a potential treatment for reactive arthritis