Combined antibiotic therapy using intravenous clindamycin and oral tetracycline may be useful in the management of active rheumatoid arthritis (RA), according to a single-blind randomized trial in the Journal of Rheumatology.¹

In the 1-year trial, 21 patients with active RA despite second-line treatment were randomized to receive either combination antibiotic therapy or no additional therapy. The 12-month antibiotic regimen comprised oral tetracycline 250 mg twice daily, 3 times per week, and intravenous clindamycin (300, 300, 600, 600, and 900 mg) infused on 5 consecutive days followed by weekly infusions of 900 mg for 3 weeks and then infusions every 2 weeks for the remainder of the 12 months. The primary outcome measure was the ACR 20 response at the end of the initial treatment period of 12 months when antibiotics were withdrawn. The subjects were followed for an additional 6 months.

Five patients in the treatment group achieved an American College of Rheumatology 20% (ACR 20) response at 1 year compared to none in the control group (P = .004). Moreover, eight patients in the treatment group and one in the control group had a >20% improvement in tender joint count (P = .008). There were also significant differences between the two groups in physician and patient global assessments. Nine patients in the treatment group completed the 6-month follow-up, of whom three sustained an ACR 20 response. Two patients lost their ACR 20 response by 18 months, supporting the authors' assertion that the antibiotics were helping control RA activity.

"Further study of this therapy, including a double-blind, placebo-controlled trial, is justified," conclude the researchers, led by Luke L. Gompels, MRCP, of Charing Cross Hospital in London, UK. It is still not clear how the antibiotic combination affects RA, but the authors propose several potential mechanisms, including a modulation of metalloproteinase activity, alteration of bowel flora, and possible effects on lymphocyte function.

Do antibiotics have a role in RA?

There has long been interest in the use of antibiotics as a treatment for RA, and previous studies have suggested that antibiotic therapy is beneficial. CIAOMed recently reported on a study published in the February issue of Arthritis & Rheumatism² that showed that initial treatment with methotrexate (MTX) plus doxycycline is more effective than MTX alone among patients with early seropositive RA.

In the 2-year double-blind randomized controlled trial, 66 patients with seropositive RA of <1 year duration who had not been previously treated with disease-modifying antirheumatic drugs (DMARDs) were randomized to one of three groups: 100 mg of doxycycline twice daily with MTX (high-dose doxycycline group); 20 mg of doxycycline twice daily with MTX (low-dose doxycycline group); or placebo with MTX (placebo group). Treatment was begun with an MTX dosage of 7.5 mg/week and titrated every 3 months until patients achieved remission or attained the maximum dosage of 17.5 mg/week. The primary endpoint was an ACR 50 response at 2 years.

At 2 years, 41.6% of patients in the high-dose doxycycline group achieved an ACR 50 response, as did 38.9% of patients in the low-dose doxycycline group and 12.5% of patients in the placebo group. Four patients in the high-dose doxycycline group, two patients in the low-dose doxycycline group, and two patients in the placebo group withdrew due to toxic reactions.

References

1. Gompels LL, Smith A, Charles PJ, et al. Single-blind randomized trial of combination antibiotic therapy in rheumatoid arthritis. J Rheumatol. 2006;33:224-227.
2. O'Dell JR, Elliot JR, Mallek JA, et al. Treatment of early seropositive rheumatoid arthritis: Doxycycline plus methotrexate versus methotrexate alone. Arthritis Rheum. 2006;54:621-627.