Background Scleroderma is an autoimmune disorder mainly characterized by progressive dermal and vascular fibrosis. It has been reported that abnormal signaling through the platelet derived growth factor (PDGF) and transforming growth factor beta (TGF-β) plays a constitutive role in the pathogenesis of the scleroderma and pulmonary arterial hypertension (PAH) including activation of fibrosis or vasculature remodeling1). Imatinib mesylate as a tyrosine kinase inhibitor of the PDGF receptor and c-Abl, can inhibit signaling pathway involved in both PDGF and TGF-β. Efficacy of imatinib has been shown to be more pronounced in patients with greater hemodynamic impairment, and imatinib has been shown to be effective in patients who remain symptomatic despite optimized treatment with established PAH drugs, although imatinib has not been approved for the use in PAH2). However, it remains to be elucidated whether the efficacy of imatinib differs according to underlying etiologies of PAH.
Objectives To assess the therapeutic effect of imatinib in scleroderma associated PAH (SSc-PAH) comparing with idiopathic/heritable PAH (I/HPAH)
Methods Eight patients with PAH (5 SSc-PAH and 3 I/HPAH) in WHO functional class III receiving at least 2 PAH agents were treated with imatinib (100-400 mg daily) for 6 months. Right heart catheterization (RHC) and pulmonary function testing (PFT) were performed at baseline and 3 or 6 months after starting imatinib treatment.
Results Seven patients underwent RHC and PFT at 6 months; 1 IPAH patient underwent RHC and PFT at 3 months and died from an exacerbation of right heart failure within 6 months. Diffusing capacity of lung for carbon monoxide (DLCO) was measured in all except 1 SSc-PAH patient whose vital capacity of lung was too small for the measurement of DLCO. There were no differences in the maintenance dose of imatinib between SSc-PAH patients and I/HPAH patients (180.0±130.4 mg/day versus 166.7±57.7 mg/day). Baseline pulmonary vascular resistance (PVR) and DLCO were lower in SSc-PAH patients than in I/HPAH patients, although the differences were insignificant (920.4±429.1 dyne s cm-5 versus 1417.3±664.2 dyne s cm-5, 30.1±6.0% versus 66.7±28.0%). Hemodynamic assessments revealed that improvements in PVR and pulmonary arterial pressure were greater in patients with SSc-PAH than in those with I/HPAH; differences were significant for PVR only (-28.0±21.5% versus 1.8±7.0%, P=0.04, -13.0±12.1% versus -0.1±4.8%, P=0.09 respectively). There were no significant differences in the improvement of DLCO between SSc-PAH patients and I/HPAH patients (8.3±6.6% versus 5.9±2.4%), however DLCO of overall patients significantly increased by 7.3 mmHg (N=7, P<0.01) as shown previously3).
Conclusions The data presented here suggests that patients with SSc-PAH may benefit more from treatment than those with I/HPAH. Further large trials are needed to assess the efficacy of imatinib in patients with SSc-PAH compared with other etiologies of the disease.
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Disclosure of Interest None Declared
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