IntroductionTyrosine kinase inhibitors (TKI) are medications of interest in the treatment of Systemic Sclerosis (SSc) because of their ability to inhibit pathways involved in fibrosis. In this open-label pilot trial, our objectives were to assess the safety, efficacy, and molecular change associated with treatment of patients with diffuse cutaneous (dc)SSc with the TKI nilotinib (Tasigna™).MethodsTen adult patients with early dcSSc were treated with nilotinib. Primary endpoints were safety and change in modified Rodnan Skin Score (MRSS) after 6 months. Lesional skin biopsies at baseline, 6 and 12 months of treatment were assessed by histopathology, immunohistochemistry, and DNA microarray.ResultsPatients had early and active dcSSc with median disease duration of 0.7 years (range 0.5, 1.7) and increasing MRSS in the month prior to baseline (mean +2.9, p=0.02). Seven out of ten patients completed 6 and 12 months of treatment. Seventy-one adverse events (AEs) including 2 serious AEs were observed, and 92 % of AEs were grade 1-2. Two patients discontinued the medication due to mild QTc prolongation. MRSS improved by a mean of 4.2 points (16 %) at 6 months and by 6.3 points (23 %) at 12 months in the 7 completers, p=0.02 and 0.01, respectively. Patients with a decrease in MRSS >20 % from baseline at 12 months (classified as improvers) had significantly higher expression of transforming growth factor beta receptor (TGFBR) and platelet-derived growth factor receptor beta (PDGFRB) signaling genes at baseline than non-improvers, and the expression of these genes significantly decreased in improvers post-treatment.ConclusionNilotinib was well tolerated by the majority of patients in this study, with tolerability limited primarily by mild QTc-prolongation. Significant MRSS improvement was observed in these early, active patients, but is not conclusive of treatment effect given the open-label study-design and small number of patients in this pilot study. Improvers had higher levels of expression of genes associated with TGFBR and PDGFRB signaling at baseline, and a significant decrease in the expression of these genes occurred only in patients with higher MRSS improvement. The findings of this pilot study warrant more conclusive evaluation.Trial registrationClinicaltrials.gov NCT01166139, July 1, 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0721-3) contains supplementary material, which is available to authorized users.

Objective. Studies suggest that hormonal states affect disease characteristics in women with rheumatoid arthritis (RA). This study investigated how age at menopause affects disease in women presenting with early RA. Methods. This was a cross-sectional study of postmenopausal women with early RA under age 65 years at time of enrollment in the Canadian Early Arthritis Cohort. RA-related disease characteristics in women who had early age at menopause (EM; age at menopause <45 years) were compared to those who had usual age at menopause (age at menopause ‡45 years). The t-test was applied to continuous variables and the chi-square test to categorical variables. Multivariate logistic regression analysis was used to adjust for age at menopause, smoking, and use of exogenous hormones. Results. A total of 534 women were included; 93 were in the EM group. The age at RA onset was similar between groups. The EM group had higher mean patient global and pain scores and was more likely to be rheumatoid factor (RF) positive and meet the 1987 American College of Rheumatology criteria for RA. Using multivariate logistic regression, the EM group was more likely to be RF positive (odds ratio 2.2 [95% confidence interval 1.3-3.8], P 5 0.005). Symptom duration, joint counts, Disease Activity Score in 28 joints, Health Assessment Questionnaire scores, and inflammatory markers did not differ between groups. Conclusion. These data suggest that early age at menopause, compared to usual age at menopause, is associated with seropositivity in women with early RA.

Objective Although new treatments for rheumatoid arthritis (RA) are extremely effective in preventing disease progression, rates of total knee replacement (TKR) continue to rise. The ongoing need for TKR is problematic, especially as functional outcomes have been reported to be worse than in patients with osteoarthritis (OA). The purpose of this study is to assess pain, function, and quality of life 2 years after TKR in a contemporary RA patients, compared to patients with OA. Methods Primary TKR cases enrolled between 5/1/2007 and 7/1/2010 in a single institution TKR registry were eligible for this study. Validated RA cases were compared to OA at baseline and at 2-years. Results We identified 4,456 eligible TKRs, including 136 RA. Compared to OA, RA TKR had significantly worse pre-operative WOMAC pain (55.9 vs. 46.6; p-value<0.0001) and function (58.7 vs. 47.3; p-value<0.0001) , however there were no differences at 2 years. Within RA, there was no difference for patients who used biologic DMARDs vs. those who did not in pain (p-value= 0.41) or function (p-value= 0.39) at 2 years. In a multivariate regression, controlling for multiple potential confounders, there was no independent association of RA with 2-year pain (p-value=0.18) or function (p-value=0.71).Satisfaction was high for both RA and OA. Conclusion RA patients undergoing primary TKR have excellent 2-year outcomes, comparable to OA, in spite of worse pre-operative pain and function. In this contemporary cohort, RA is not an independent risk factor for poor outcomes.

Contemporary patients with RA have significant improvements in pain and function after THR, but higher proportions have worse 2-year pain and function. In addition, RA is an independent predictor of 2-year pain and poor function after THR, despite high use of disease-modifying therapy.