HOUSTON – Use of a gonadotropin-releasing hormone antagonist showed early promise as a novel therapy for rheumatoid arthritis in a brief, proof-of-concept study that was presented at the annual meeting of the Endocrine Society.
Five days of subcutaneous injections of cetrorelix (Cetrotide) that were aimed at rapidly reducing levels of luteinizing hormone and follicle-stimulating hormone safely improved signs and symptoms of RA and reduced tumor necrosis factor–alpha levels in a 99-patient, placebo-controlled, randomized trial. Larger and longer-term clinical trials of GnRH antagonists as a potential treatment for RA are planned, according to Dr. Anita Kass of Betanien Hospital in Skien, Norway.
All study participants had active RA and were on stable doses of disease-modifying antirheumatic drugs. They were randomized to placebo or subcutaneous cetrorelix dosed at 5 mg on days 1-3 and 3 mg on days 4-5.
Outcomes were assessed on day 5, when LH and FSH levels in the cetrorelix arm were at their nadir. At that time, an ACR 20 (American College of Rheumatology scale, based on a 20% improvement in specified criteria) response was documented in 40% of patients on cetrorelix, compared with 18% of controls. Remission according to the DAS28 (Disease Activity Score, including a 28-joint count) was achieved in 13% of patients on the GnRH antagonist, compared with none on placebo. The erythrocyte sedimentation rate had declined by a mean of 1.06 mm/hour, compared with baseline, in the active treatment group, compared with a 5.04-mm/hour increase in controls.
In addition, the cetrorelix group had a mean 0.58 log pg/mL decrease in TNF-alpha compared with baseline, whereas controls experienced a 0.02 log pg/mL reduction. All of these differences between the cetrorelix and control groups were statistically significant.
The reduction in DAS28 score by day 5 was 0.82 in the cetrorelix group and 0.57 in controls, a trend that didn’t reach significance.
Adverse events in the two study arms did not differ.
Dr. Kass credited the impetus for this line of clinical investigation to earlier work by other investigators at the Weizmann Institute of Science in Rehovot, Israel. They showed that GnRH and GnRH-II are produced by T cells, and that the hormones have roles that extend beyond the reproductive system to include immune system regulation. The hormones trigger T-cell chemotaxis and homing to specific organs (Nat. Med. 2002;8:1421-6).
This proof-of-concept study was supported by the Norwegian Health and Rehabilitation Organization. The presenter reported having no financial conflicts.