Background/Purpose: Imatinib mesylate (IM) has been shown to decrease fibrosis in preclinical models and is a treatment of interest for Systemic Sclerosis (SSc).   We have previously reported the results of our open label trial.  In that study, 24/30 of patients tolerated 1 year of therapy and demonstrated a 22% improvement in the Modified Rodnan Skin Score (MRSS) as well as improvement or stability in measures of pulmonary function.  Patients from the initial phase of that trial were eligible to continue treatment with IM in a 24 month extension phase of this open label trial.

Methods: This was a phase IIa, open-label, single-arm clinical trial in extension-phase.  Patients with dcSSc were treated with imatinib at 200 to 400 mg daily and were assessed every 3 months for safety, MRSS, and measurement of additional outcome measures for an additional 24 mos.  Pulmonary function testing, high resolution CT of the chest, and echocardiography were performed as part of standard clinical care.

Results: 24 patients completed the 12 month initial phase of the imatinib trial.  17/24 patients enrolled in the extension phase and 13 continued treatment with imatinib for 24 months.  The median age was 48 (18,61).  76% were female.  65% were Caucasian.  The mean disease duration from the first non-Raynaud’s symptom of SSc was 2.7 ± 2.1 years in this group at the time of enrollment in the initial phase.  29% were anti-scl70-positive.  The baseline MRSS was 23.8 ± 9.2 at the start of the extension phase.  Patients who entered the extension phase had experienced a mean improvement in MRSS of 7.1±4.8 points during the initial one year trial.

92 AEs were recorded, 43% of which were felt to be at least possibly related to IM and these were all Grade 1 or 2.  7 SAEs occurred, none of which were felt to be related to the IM.  The most frequently noted side effects were muscle pain, fatigue, nausea, and edema. 

The MRSS decreased from a median of 24 (IQR 18, 31) at the beginning of the extension phase to 18 (13, 29) after an additional 12 months of IM extension (n=15, p=0.08) and to 16 (13, 24) with an additional 24 mo of IM extension (n=13, p=0.002.)  In 12 patients, the FVC at baseline of extension was 92 (71.0, 105.0) and was 85 (67.0, 105.0) % predicted after 24 months, p=0.09.  The hemoglobin adjusted DLCO at baseline was 77% predicted (63.0, 108.0) and was 74.5% (53.5, 92.0) at 24 mo, p=0.019.  When the subgroup of patients with ILD is examined (n=6), the FVC is 61% (59.0, 90.0) at baseline and 62.5% (54.5, 70.0) at 24 mo, p=0.25, and the DLCO is 63% (55.0, 63.0) to 50% (46.0, 53.5), p=0.13.  Two patients developed incident mild interstitial lung disease as seen on CT during the 24 month period of follow-up.  Significant changes were not observed in ESR, SHAQ, or SF-36 mental and physical components.

Conclusion: A total of 36 months of imatinib treatment was tolerable to a subset of patients with dcSSc.   Although improvement in MRSS is observed in this subset, conclusions cannot be drawn regarding efficacy given the open label nature of this study.  The utility of imatinib and/or other TKIs should be evaluated in a controlled fashion to better evaluate efficacy in the treatment of SSc patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/imatinib-mesylate-gleevec-in-the-treatment-of-diffuse-cutaneous-systemic-sclerosis-results-of-a-24-month-open-label-extension-phase/