BOSTON, Massachusetts—A late-breaking poster presented at the American College of Rheumatology 2007 meeting showed that topical nitroglycerin might be a realistic alternative for patients with Raynaud's phenomenon (RP).¹

A research group led by Christopher P. Denton, MD, with the Royal Free Hospital in London, England, reported a multicenter crossover study of MQX-503, a new topical formulation of nitroglycerin being developed by MediQuest Therapeutics, Inc.

"A topical nitroglycerin that is not systemically absorbed would be an attractive option for Raynaud's phenomenon, since 12% to 15% of patients are young women, in whom I would try to avoid systemic medications of all kinds," coinvestigator Frederick M. Wigley, MD, told Musculoskeletal Report. "A topical formulation might be appropriate for those with mild disease or as an adjunct to systemic therapy in those with more severe disease," said Dr. Wigley, in the division of rheumatology at Johns Hopkins University in Baltimore.

MQX-503 is a topical microemulsion of nitroglycerin, designed to induce local vasodilatation with minimal systemic effects. The investigators tested it as treatment for primary or secondary RP in a multicenter, double-blind, randomized, vehicle-controlled, crossover study. The primary outcome measure was the Raynaud's condition score (RCS).

The researchers observed for 2 weeks 109 patients with moderate-to-severe RP who were randomized to receive for 3 weeks either vehicle or 0.9% MQX-503. Patients subsequently crossed over for a further 3 weeks to the other study medication. Patients recorded symptoms in an electronic diary at each medication application and/or RP event.

Of the 109 patients randomized (90% female, N = 56 vehicle first, N = 53 MQX-503 first), eight discontinued treatment. The intention-to-treat (ITT) analysis showed the mean baseline RCS was 39. Mean RCS for patients treated with MQX-503 was lower (29.2) than for the patients treated with vehicle (31.7, P = .008). For patients actually treated per protocol, baseline RCS was 39.5, decreasing to 29.4 with MQX-503 versus 32.7 with vehicle (P <.001). The 49 patients in the scleroderma subgroup also demonstrated an improvement in RCS when treated with MQX-503 versus when treated with vehicle (P = .03).

The crossover design permitted differences in treatments between drug and placebo to be analyzed for each individual patient. Dr. Wigley said that improvement in 30 patients' RCS on MQX-503 was at least 25% greater than on vehicle, but was greater in only 17 patients with vehicle than with drug. Absolute differences also favored MQX-503 with 29 (42%) having at least a 20-point improvement in RCS on active treatment compared with 16 (23%) on vehicle. There were two serious adverse events (AEs), neither related to the study medication. AEs, including headache and dizziness, did not differ between vehicle and MQX-503.

A second positive study of this nitroglycerin formulation was presented orally by Lorinda Chung, MD.² That multicenter "in life" study included 318 patients, all of whom had at least five Raynaud attacks in a 7-day baseline disease period, and randomized them to either placebo or 1% MQX-503. The primary outcome measure was change in mean RCS.

Dr. Chung reported, "MQX-503 improved the RCS more than placebo, with a statistically significant effect in the ITT population and in the subgroup of secondary RP. MQX-503 resulted in greater benefit during the early [winter season] compared with late enrollment period and in patients with primary compared with secondary RP."

Dr. Wigley said that MQX-503 reduces severity of RP and is well tolerated. He suggested that the new microemulsion formulation might offer an alternative to the AEs, such as headache, flushing, and lightheadedness, associated with the calcium channel blockers and nitroglycerin ointments commonly prescribed for RP.

References