[2008] [SAT0218] THE EFFECTS OF SITAXENTAN (A HIGHLY-SELECTIVE ENDOTHELIN RECEPTOR ANTAGONIST) IN SCLERODERMA-ASSOCIATED PULMONARY ARTERIAL HYPERTENSION (SSC-PAH) ARE ANALOGOUS TO THOSE SEEN IN IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION (IPAH)
J.E. Pope1, S. Mehta2 1Departments of Medicine, Division of Rheumatology, and Epidemiology and Biostatistics, University of Western Ontario; 2Departments of Medicine, Southwest Ontario Pulmonary Hypertension Clinic, Divisions of Respirology and Cardiology, London, Canada
Background: Pulmonary arterial hypertension (PAH) is an increasingly recognised complication of connective tissue diseases (CTD) and is a leading cause of death in scleroderma (SSc). SSc-PAH is generally regarded as less responsive to treatment compared to iPAH. Endothelin (ET-1) levels are increased in SSc-PAH. Sitaxentan is a once daily, oral, highly-selective (6500:1 - ETA:ETB) ET receptor antagonist (ETRA). ETRAs have been shown to be effective in iPAH and in SSc-PAH; however, SSc patients may respond less well as they are older than iPAH and have severe vasculopathy with less complaints of dyspnoea.
Objectives: The aims of this study were to compare the proportion of patients with SSc-PAH vs iPAH who responded to long-term sitaxentan treatment (change in WHO functional class [FC]), and to compare time to clinical worsening in SSc-PAH vs iPAH patients.
Methods: STRIDE-2 was a randomised, placebo-controlled, 18-week, multi-centre study in PAH FC I-IV). A total of 245 patients were randomised to: sitaxsentan 50 mg QD, sitaxentan 100 mg QD, bosentan 125 mg BID, or placebo. At 18 weeks, patients continued in the open-label STRIDE-2X study. Patients on sitaxentan 100 mg QD or bosentan 125 mg BID continued on the same dose, while the placebo group was randomised to sitaxentan 100 mg QD or bosentan 125 mg BID, and patients receiving sitaxentan 50 mg were increased to 100 mg QD.
Results: In total, 145 patients in STRIDE-2X received sitaxentan 100 mg QD. Most were women of whom 89 (61%) had iPAH and 42 (29%) had CTD-PAH (SSc, 29; overlap, 8; SLE, 5). SSc-PAH were older than iPAH (mean age: 64 vs 56 years). Baseline 6MWD was 322+88 m (±SD) in SSc-PAH compared with 355±74 m for iPAH. Mean PAP was lower in SSc-PAH versus IPAH patients (40±10 mmHg vs 47±12 mmHg, respectively; p=0.006) at baseline, whereas, mean PVR and CI values were similar between groups. More patients with iPAH were in FC III (60%) compared with SSc-PAH patients (48%) at baseline; 45% of those with SSc-PAH were in FC II vs 36% with iPAH. Overall, 77% of SSc-PAH and iPAH completed 1 year sitaxentan monotherapy. At study end, 90% of the SSc-PAH group improved at least one FC (28%) or remained unchanged (62%), and 91% of iPAH improved at least one FC (21%) or remained unchanged (70%). Worsening in FC at Week 52 (vs baseline) occurred in 10% of SSc-PAH and in 9% with iPAH, p=NS. Time to clinical worsening, survival and discontinuation rates were not different between SSc-PAH and iPAH over 52 weeks.
Conclusion: The response to sitaxentan monotherapy over 1 year was similar between SSc-PAH and iPAH patients, despite baseline differences including worse baseline 6MWD in SSc-PAH and more SSc-PAH patients in FC II. Overall, sitaxentan was well tolerated and effective in SSc-PAH. However, patients with SSc-PAH may do better if detected early (before 6MWD is so reduced), so a high awareness from rheumatologists is paramount.
Ann Rheum Dis 2008;67(Suppl II):502
Scleroderma, Myositis and related syndromes
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