Wei-Ti Huang

Nilotinib (Tasigna™) in the treatment of early diffuse systemic sclerosis: an open-label, pilot clinical trial

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.

Patients with Rheumatoid Arthritis Are More Likely to Have Pain and Poor Function After Total Hip Replacements than Patients with Osteoarthritis

Objective. Total hip replacement (THR) outcomes have been worse for patients with rheumatoid arthritis (RA) compared with those who have osteoarthritis (OA). Whether this remains true in contemporary patients with RA with a high use of disease-modifying and biologic therapy is unknown. The purpose of our study is to assess pain, function, and quality of life 2 years after primary THR, comparing patients with RA and patients with OA. Methods. Baseline and 2-year data were compared between validated patients with RA and patients with OA who were enrolled in a single-center THR registry between May 1, 2007, and February 25, 2011. Results. There were 5666 eligible primary THR identified, of which 193 were for RA. RA THR had worse baseline Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain (44.8 vs 53.2, p < 0.001) and function (38.7 vs 49.9, p < 0.001) compared with OA. These differences remained after surgery: pain (88.4 vs 94.0, p < 0.001) and function (82.9 vs 91.8, p < 0.001). Patients with RA were as likely to have a significant improvement as patients with OA (Δ WOMAC > 10) in pain (94% vs 96%, p = 0.35) and function (95% vs 94%, p = 0.69), but were 4 times as likely to have worse function (WOMAC ≤ 60; 19% vs 4%, p < 0.001) and pain (12% vs 3%, p < 0.001). In multivariate logistic regression controlling for multiple potential confounders, RA increased the odds of poor postoperative function (OR 4.32, 95% CI 1.57–11.9), and in patients without a previous primary THR, worse postoperative pain (OR 3.17, 95% CI 1.06–9.53). Conclusion. 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.

Short-term total hip replacement outcomes in ankylosing spondylitis.

BackgroundWhile rates of total hip replacement (THR) in spondyloarthritis are increasing, contemporary outcomes are not well described. ObjectivesThis study analyzes 2-year outcomes in a contemporary cohort of ankylosing spondylitis (AS) patients undergoing THR. MethodsA case-control study was performed using data from an institutional arthroplasty registry. Validated AS cases were matched 4:1 by age and procedure to patients with osteoarthritis (OA). Data were obtained prior to surgery and at 2 years. Multiple imputation techniques were performed to avoid systematic bias due to missing data. ResultsThirty eligible AS cases were identified between May 2007 and February 2010. Ankylosing spondylitis cases had worse American Society of Anesthesia class (P < 0.001) and more comorbidities (P = 0.02) compared with OA. Ankylosing spondylitis had worse preoperative lower-extremity Western Ontario and McMaster Universities Arthritis Index pain (46.8 vs 55.4; P = 0.03), function (43.0 vs 55.1; P = 0.04), and general health status measured as SF-12 (Short-Form Health Survey) physical component scale (PCS) score (29.6 vs 36.0; P < 0.001), however, there was no difference at two years in pain (89.4 vs 92.5; P = 0.23) or function (83.9 vs 90.1; P = 0.04). Physical component scale score remained significantly worse (41.2 vs 50.1; P < 0.001). Better preoperative SF-12 PCS score significantly decreased the risk of a poor pain outcome (odds ratio, 0.06; 95% confidence interval, 0.01–0.40). Overall satisfaction was high. ConclusionsAlthough patients with AS in a contemporary cohort have more comorbidities and worse physical function prior to THR, they achieve similar gains as OA. In a multivariate regression controlling for multiple potential confounders including back pain, only preoperative health status measured as SF-12 PCS score was a significant risk factor for a poor 2-year pain. Among contemporary patients, AS is not an independent risk factor for poor THR outcomes.Take-Home MessagePatients with AS have significant improvement in pain and function after THR.Poor preoperative function and low-back pain are not risk factors for poor THR outcomes for patients with AS.Despite improvements, low SF-12 PCS scores indicate persistent limitations due to health.

Effectiveness of rituximab for the otolaryngologic manifestations of granulomatosis with polyangiitis (Wegener's).

Ear, nose, and throat (ENT) involvement is the most prevalent manifestation of granulomatosis with polyangiitis (Wegeners) (GPA) and correlates with permanent damage and decreased quality of life. Although prior studies have evaluated the efficacy of rituximab (RTX) for granulomatous features of GPA, none have evaluated its efficacy solely for ENT manifestations. We compared the effectiveness of RTX to other therapies for the ENT manifestations of GPA in a large, well‐characterized cohort.

SAT0020 Rheumatoid Arthritis (RA) Patients Have Similar Excellent Outcomes After Total Knee Replacement Compared with Osteoarthritis (OA) Patients

Background Rheumatoid arthritis (RA) patients have worse reported outcomes after total knee replacement (TKR) as compared with osteoarthritis (OA) patients. It is unknown if this persists in a contemporary cohort of RA patients with high DMARD and biologic use. Objectives To compare baseline and 2 year outcomes of primary and revision TKR (RTKR) in patients with RA versus OA. Methods All TKR and RTKR enrolled in a single institution registry between 5/1/2007 and 7/1/2010 with pre-operative data and who were alive at two years were eligible for this analysis. Patients with two eligible procedures only contributed data from the second. RA cases were identified by self report or ICD-9 code and validated by chart review. Patients with ICD-9 codes for other systemic rheumatic disease or fractures were excluded. Satisfaction at 2 years was measured on a 5-point Likert scale. Differences between groups were compared using unpaired Student’s t test, Chi-Square or Fisher’s exact test as appropriate. Results 5,384 primary TKR and 374 RTKR were eligible for this study with 178 RA TKR and 32 RA RTKR. 94% had 2-year follow-up. (Table 1) More TKR RA cases were female with lower BMI and more comorbidities. 81% of RA TKR were on DMARD therapy, 44% on biologics; RTKR 87% and 50% respectively. RA TKR had significantly worse pain and function pre-operatively but no difference at 2 years. RA and OA had similar clinically meaningful improvements in pain and function, (WOMAC change >10) and similar numbers of patients with poor 2-year outcomes (WOMAC pain or function≤ 60). Satisfaction was high for both groups. For RTKR, OA and RA patients had similar pain and function pre-operatively, but RA had significantly less pain and better function at 2 years. OA RTKR were much less satisfied at 2 years. Conclusions Although contemporary RA patients undergoing TKR have worse pre-operative pain and function compared with OA patients, they have comparable 2 year outcomes. By contrast, RTKR RA patients have less pain and better function at 2 years than OA RTKR- differences which were clinically meaningful. These data demonstrate excellent results in contemporary RA TKR and RTKA patients. Disclosure of Interest None Declared

Short-Term Total Hip Arthroplasty Outcomes in Patients With Psoriatic Arthritis or Psoriatic Skin Disease Compared to Patients With Osteoarthritis

Outcomes of total hip arthroplasty (THA) in patients with psoriasis have been poorly studied. This study was undertaken to assess whether patients with psoriatic arthritis (PsA) or those with cutaneous psoriasis (PsC) without evidence of inflammatory joint disease are at an increased risk for worse outcomes after THA as compared to patients with osteoarthritis (OA).

Short Term Total Hip Arthroplasty Outcomes in Patients with Psoriatic Arthritis, Psoriasis Skin Disease, and Osteoarthritis

Outcomes of total hip arthroplasty (THA) in patients with psoriasis have been poorly studied. This study was undertaken to assess whether patients with psoriatic arthritis (PsA) or those with cutaneous psoriasis (PsC) without evidence of inflammatory joint disease are at an increased risk for worse outcomes after THA as compared to patients with osteoarthritis (OA).

A3.32 Efficacy of rituximab for the otolaryngologic manifestations of granulomatosis with polyangiitis

Objective Otolaryngologic (ENT) involvement is the most prevalent manifestation of Granulomatosis with Polyangiitis (GPA) and correlates with permanent damage and decreased quality of life. Although prior studies have evaluated the efficacy of rituximab (RTX) for granulomatous features of GCA, none have evaluated its efficacy solely for ENT manifestations. We compared the efficacy of RTX to other therapies for the ENT manifestations of GPA. Methods A retrospective analysis of 975 visits from 99 GPA patients seen at a tertiary care ENT practice between 2003 and 2013. At each visit subjects had complete ENT exam with ENT activity assessed by a single expert otolaryngologist. ENT disease activity at each visit in subjects on RTX was compared to those on all other therapy. Results 48 subjects never received RTX and 51 received RTX at least once. There was no active ENT disease at 92.4% of visits for subjects on RTX compared to 53.7% of visits for subjects not receiving RTX (OR 11.0; 95% CI 5.5–22.0, p<0.0001). Subjects on RTX compared to methotrexate, azathioprine, cyclophosphamide or trimethoprim-sulfamethoxazole were significantly more likely to be in ENT remission, p<0.0001 for each comparison. Conclusion RTX is an effective treatment for ENT manifestations of GPA. Subjects treated with RTX were significantly less likely to have active ENT disease compared to those not on RTX. Patients being treated with RTX were 11 times less likely to have active ENT disease than patients being treated with other therapies.

Comparison of change in end tidal carbon dioxide after three minutes of step exercise between systemic sclerosis patients with and without pulmonary hypertension

Objectives. Pulmonary hypertension (PH) is an important cause of morbidity and mortality in patients with SSc. The submaximal heart and pulmonary evaluation (step test) is a non-invasive, submaximal stress test that could be used to identify SSc patients with PH. Our aims were to determine whether change in end tidal carbon dioxide (▵PETCO2) from rest to end-exercise, and the minute ventilation to carbon dioxide production ratio (·VE/·VCO2), both as measured by the step test, differ between SSc patients with and without PH. We also examined differences in validated self-report questionnaires and potential PH biomarkers between SSc patients with and without PH. Methods. We performed a cross-sectional study of 27 patients with limited or dcSSc who underwent a right heart catheterization within 24 months prior to study entry. The study visit consisted of questionnaire completion; history; physical examination; step test performance; and phlebotomy. ▵PETCO2, ·VE/·VCO2, self-report data and biomarkers were compared between patients with and without PH. Results. SSc patients with PH had a statistically significantly lower median (interquartile range) ▵PETCO2 than SSc patients without PH [−2.1 (−5.1 to 0.7) vs 1.2 (−0.7 to 5.4) mmHg, P = 0.035], and a statistically significantly higher median (interquartile range) ·VE/·VCO2 [53.4 (39–64.1) vs 36.4 (31.9–41.1), P = 0.035]. There were no statistically significant differences in self-report data or biomarkers between groups. Conclusion. ▵PETCO2 and ·VE/·VCO2 as measured by the step test are statistically significantly different between SSc patients with and without PH. ▵PETCO2 and ·VE/·VCO2 may be useful screening tools for PH in the SSc population.

Pregnancy Does Not Adversely Affect Postoperative Pain and Function in Women With Total Hip Arthroplasty.

Age at time of THA, mean (SD), y 35 (7.9) 40.7 (4.3) 37.3 (4.3) <0.001 Time fromTHA to survey response,mean (SD),mo 36.5 (27.3) 34.9 (11.7) 39.5 (15.6) 0.24 Preoperative bodymass index, mean (SD), kg/m 25.6 (5.9) 25.4 (4.9) 23.6 (2.0) Race, n (%) 0.35 White 63 (81) 69 (85) 9 (90) Hispanic 12 (16) 6 (8) 1 (10) 0.29 Education level, n (%) 0.83 High school 4 (6) 4 (6) 2 (20) College graduate/advanced degree 50 (63) 53 (65) 5 (50) Reason for THA surgery, n (%) 0.17 Inflammatory arthritis 24 (30) 12 (15) 4 (40) Osteoarthritis 18 (23) 24 (30) 3 (30) Fracture 4 (5) 4 (5) 1 (10) Congenital hip dysplasia 21 (27) 25 (31) 2 (20) Osteonecrosis 10 (13) 16 (20) 0 Other 2 (2) 0 0 Primary THA, n (%) 67 (85) 77 (96) 10 (100) 0.31 Deyo comorbidity 0.69 0 61 (78) 66 (84) 5 (83) >1 17 (22) 13 (16) 1 (17) WOMAC pain Pre-THA, mean (SD) 50.5 (20.2) 50.4 (18.0) 60.0 (15.8) 0.61 Post-THA, mean (SD) 85.2 (18.8) 84.9 (15.8) 92.5 (5.9) 0.4 WOMAC function Pre-THA, mean (SD) 48.9 (20.3) 51.7 (18.3) 54.7 (15.8) 0.63 Post-THA, mean (SD) 87.6 (22.1) 91.1 (15.3) 93.5 (6.4) 0.39 Expectation score, mean (SD) 81.1 (14.7) 86.5 (12.9) 86.8 (12.8) 0.13 Overall THA satisfaction 0.62 Very satisfied, n (%) 40 (87) 70 (86) 9 (90) Very dissatisfied, n (%) 0 1 (1) 0 Improvement in quality of life post-THA 0.68 Great improvement, n (%) 42 (53.1) 42 (51.2) 6 (60) C hanging indications and utilization patterns have resulted in shifting demographics of patients receiving total hip arthroplasty (THA) to include younger patients, including women of childbearing potential. There have been concerns that pregnancy following THA could result in prosthetic loosening, dislocation, pain, or functional impairment. While several case series report successful pregnancies following THA, less is known about the effects of pregnancy on pain or function associated with the maternal hip prosthesis. Using a well-characterized cohort from a THA registry at a single highvolume specialty hospital, we compared preoperative and postoperative measures of pain and function in 3 groups of women: those with only pre-THA pregnancies, those with pregnancy post-THA, and those without any pregnancy. Our primary objective was to compare postoperative pain and function in women with different pregnancy histories. Women aged 18 to 45 years enrolled in an institutional THA registry from 2007 to 2011 were identified. Subjects had preoperative pain and function data collected as part of the registry. For this study, subjects received a questionnaire eliciting pregnancy history (defined as gestation lasting >30 weeks) with additional questions about postarthroplasty pain and function. The primary outcomes of interest were postoperative Western Ontario and McMaster UniversitiesOsteoarthritis Index (WOMAC) pain and function scores (0–100, with higher scores indicating better function and less pain). Secondary objectives included pregnancy outcomes, comparing those who had pre-THA pregnancy to those who had postTHA pregnancy. Of 325 eligible women undergoing THA in the study period, 171 women (52.6%) responded to the pregnancyfocused questionnaire. Comparing responders to nonresponders, there were no statistically significant differences between groups in terms of demographics or preoperative baselineWOMAC pain and function scores. Of the responders, 79 women (46.2%) reported being nulliparous, 82