Aug. 29, 2003 — HLA-B27-positive patients who develop reactive arthritis (ReA) have improved long-term outcomes if treated with ciprofloxacin (Cipro) for three months at the onset of ReA, according to the results of a long-term follow-up study published in the September issue of the Annals of the Rheumatic Diseases.

"The value of antibiotics in the treatment of ReA is still controversial," write T. Yli-Kerttula, from Turku University in Finland, and colleagues. "Results for the impact of antimicrobial chemotherapy of enteric infections on the development of ReA have been contradictory."

Of 71 patients with acute ReA triggered by a gastrointestinal or urogenital infection who had participated in a double-blind, placebo-controlled trial on the effectiveness of ciprofloxacin four to seven years earlier, 53 patients returned for follow-up examination. Of 26 patients who had originally received ciprofloxacin, 20 were HLA-B27 positive, as were 25 of 27 patients originally in the placebo group.

Chronic rheumatic disease developed in 11 (41%) of 27 patients in the original placebo group and in 2 (8%) of 26 patients in the original ciprofloxacin group (P = .006). Ankylosing spondylitis developed in two patients who originally had received placebo and in none who had received ciprofloxacin. Recurrent anterior uveitis developed in three patients in the placebo group and in none in the ciprofloxacin group. Of the patients with chronic spondyloarthropathy, 10 in the placebo group and none in the ciprofloxacin group were HLA-B27 positive.

"Analysis 4-7 years after the initial ReA suggests that a three month course of antibiotics in the acute phase may have a beneficial effect on the long term prognosis," the authors write. "At present it is not possible to give a definite explanation for the results. Nevertheless, our results strongly suggest that antibiotic treatment may, after all, prevent the chronic consequences of ReA, especially in HLA-B27 positive subjects."

An EVO Grant of Turku University Central Hospital supported this study.

Ann Rheum Dis. 2003;62:880-884

Learning Objectives for This Educational Activity

Upon completion of this activity, participants will be able to: Describe the etiology and prognosis of reactive arthritis.Evaluate on the efficacy of ciprofloxacin in the short and long term in preventing reactive arthritis.

Clinical Context

Reactive arthritis represents a set of rheumatologic disorders related to a previous infection. Most of these responsible infections involve the gastrointestinal or genitourinary tracts, and causative organisms include Salmonella species, Shigella flexneri, Campylobacter jejuni, Yersinia species, and Chlamydia trachomatis. Most patients with reactive arthritis do not suffer long-term arthritis, but the authors of the current study report that 4% to 19% of affected patients will have a chronic course of the disease. Patients with the HLA-B27 gene are more likely to suffer long-term disease.

Attempts to use antibiotics to prevent long-term disease associated with reactive arthritis have met with poor results. Yli-Kerttula and colleagues, the authors of the current study, previously performed a similar trial of a three-month course of ciprofloxacin to improve the outcome of reactive arthritis. Published in the July 2000 issue of the Annals of the Rheumatic Diseases, they demonstrated that ciprofloxacin did not improve patients' self assessment, complete recovery, number of swollen joints, or erythrocyte sedimentation rate at one-year follow up. A similar trial by Sieper and colleagues, published in the July 1999 issue of Arthritis and Rheumatism, showed similar disappointing results for ciprofloxacin after three months of treatment and follow-up.

The current study evaluates the same group of patients from the original Yli-Kerttula study four to seven years later. The authors sought to determine if the ciprofloxacin therapy might carry forward some previously undiscovered positive effects on the course of reactive arthritis.

Study Highlights

The original trial involved 71 participants with acute reactive arthritis. 60 subjects had arthritis induced by a gastrointestinal infection, and 11 patients had a previous genitourinary infection.Participants were randomized to receive either ciprofloxacin 500 mg or placebo twice a day for 3 months. They were followed for 1 year in the original trial and invited to be re-evaluated 4-7 years after randomization.Investigators were not blinded to the original treatment regimen of the study subjects.Primary outcome measures of the study included a clinical examination for swollen, painful joints, laboratory evaluation, including erythrocyte sedimentation rate and serum antibody levels against specific triggering pathogens, and radiographic evaluation via magnetic resonance imaging (MRI).53 of the original 71 subjects were available for clinical analysis in the current study. 26 subjects were from the ciprofloxacin group, and 27 were from the placebo group. 85% of participants from the current study were HLA-B27 positive.2 subjects in the ciprofloxacin group were found to have suspected inflammatory back pain on clinical examination compared with 7 patients in the placebo group. Overall, 2 patients (8%) in the ciprofloxacin group developed chronic rheumatic disease, while 11 patients (41%) in the placebo group had chronic rheumatic disease. This difference attained statistical significance.10 of the 11 subjects in the placebo group with chronic rheumatic disease were HLA-B27 positive. Neither of the 2 ciprofloxacin-treated subjects with chronic disease were HLA-B27 positive.No particular microbe was an independent risk factor for chronic disease.Sacroiliitis was found on MRI in 3 patients in the placebo group but none in the ciprofloxacin group.92% of subjects in the ciprofloxacin group had recovered according to the opinions of the examining physicians compared with 59% of the placebo group, a statistically significant difference. However, patients' assessment of their own recovery was similar between the 2 groups.There were no significant differences in laboratory findings between the 2 groups.

Pearls for Practice

Reactive arthritis is caused by infection with certain bacteria and produce chronic symptoms in a minority of patients.Although previous research has demonstrated ciprofloxacin to be ineffective in preventing chronic symptoms related to reactive arthritis, the authors found some benefit four to seven years after ciprofloxacin treatment. More research will need to be conducted before a conclusion can be drawn on this controversial subject.
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