AN EXPLORATORY RESPONDER ANALYSIS IN THE SUBGROUP OF PATIENTS WITH CONNECTIVE-TISSUE–ASSOCIATED PULMONARY ARTERIAL HYPERTENSION (PAH) FROM THE SUPER-1 STUDY OF SILDENAFIL IN PAH

Background: Pulmonary arterial hypertension (PAH) is a progressive, life-threatening disease that is a frequent complication of connective tissue diseases (CTD). Outcomes are poorer in PAH-CTD compared with PAH of other etiologies. Sildenafil (Revatio®) has been shown to improve exercise capacity, evaluated as mean change in 6-minute walk distance (6MWD), in patients with PAH, including PAH-CTD patients (Badesch et al. 2007). Identifying baseline characteristics that predict response to treatment would be beneficial. Objectives: To further describe 6MWD improvements in PAH-CTD patients treated with sildenafil by examining which patients improved 6MWD by at least 10% and what baseline characteristics were associated with this level of improvement. Methods: Sildenafil 20, 40, or 80 mg three times daily (TID) was compared with placebo in a 12-week, double-blind study in adult PAH patients. 6MWD was assessed at baseline and week 12. Differences between sildenafil and placebo in the percentage of patients who improved their 6MWD by at least 10% of baseline values (``responders'') were assessed using Fisher exact tests. Mutivariate logistic regression assessed prognostic factors including treatment, baseline 6MWD, age, sex, functional class, diagnosis, and hemodynamic parameters. Three models were used, assessing PAH-CTD patients treated with (1) sildenafil 20 mg TID or placebo, (2) sildenafil (all doses combined) or placebo, and (3) sildenafil only. Results: Of 278 PAH patients in the parent study, 84 had CTD and received treatment with sildenafil 20 (n=21), 40 (n=20), or 80 mg (n=21) TID or placebo (n=22). Patients with PAH-CTD had a mean age of 53±15 years and 6MWD of 342±76 m; 17% were men; primary diagnoses included scleroderma (45%), systemic lupus erythematous (23%), and other (32%); and 38%, 61%, and 1% had World Health Organization functional class II, III, or IV disease, respectively. More patients in the combined sildenafil dose group achieved 6MWD improvement of ≥10% vs placebo (P<0.05). For sildenafil 20 mg TID, 55% of patients achieved ≥10% improvement in 6MWD vs 19% of placebo patients (P<0.05); improvements in the sildenafil 40 (39%) and 80 mg (42%) TID groups were not significant. Factors significantly predicting improved 6MWD included lower baseline 6MWD and younger age in models 2 and 3 (P<0.02); a treatment effect was present in model 2 for combined-dose sildenafil (P=0.0223) and the treatment effect of sildenafil 20 mg was borderline significant in model 1 (P=0.0623). Conclusions: In an exploratory responder analysis in the subgroup of patients with PAH-CTD from the SUPER-1 study of sildenafil in PAH, lower baseline 6MWD and younger age predicted 6MWD improvement in patients with at least 10% improvement in 6MWD. References: 1. Badesch J Rheumatology 2007;34:2417-22. Disclosure of Interest: D. Badesch Grant/Research support from: Glaxo Wellcome, United Therapeutics/Lung Rx, Actelion/CoTherix, Encysive, Myogen/Gilead, Pfizer, Lilly/ICOS, Bayer, and Novartis, Consultant for: Glaxo Wellcome/GlaxoSmithKline, Actelion/CoTherix, Berlex, Gilead/Myogen, Encysive, Pfizer, United Therapeutics/Lung Rx, Lilly/ICOS, MondoBiotech/MondoGEN/Biogen IDEC, Bayer, Arena, and Ikaria. He has also provided assistance to legal counsel for Actelion., L.-J. Hwang Employee of: Pfizer Inc, J. Cwengros Employee of: Pfizer Inc, S. Watt Employee of: Pfizer IncCitation: Annals of the Rheumatic Diseases, volume 70, supplement 3, year 2011, page 479Session: Scleroderma, Myositis and related syndromes (Poster Presentations )