Marine Meunier

Outcomes of patients with systemic sclerosis-associated polyarthritis and myopathy treated with tocilizumab or abatacept: a EUSTAR observational study

Objective To evaluate the safety and effectiveness of tocilizumab and abatacept in systemic sclerosis (SSc)-polyarthritis or SSc-myopathy. Methods 20 patients with SSc with refractory polyarthritis and seven with refractory myopathy from the EUSTAR (EULAR Scleroderma Trials and Research) network were included: 15 patients received tocilizumab and 12 patients abatacept. All patients with SSc-myopathy received abatacept. Clinical and biological assessments were made at the start of treatment and at the last infusion. Results After 5 months, tocilizumab induced a significant improvement in the 28-joint count Disease Activity Score and its components, with 10/15 patients achieving a EULAR good response. Treatment was stopped in two patients because of inefficacy. After 11 months’ treatment of patients with abatacept, joint parameters improved significantly, with 6/11 patients fulfilling EULAR good-response criteria. Abatacept did not improve muscle outcome measures in SSc-myopathy. No significant change was seen for skin or lung fibrosis in the different groups. Both treatments were well tolerated. Conclusions In this observational study, tocilizumab and abatacept appeared to be safe and effective on joints, in patients with refractory SSc. No trend for any change of fibrotic lesions was seen but this may relate to the exposure time and inclusion criteria. Larger studies with longer follow-up are warranted to further determine the safety and effectiveness of these drugs in SSc.

Body mass index influences the response to infliximab in ankylosing spondylitis

IntroductionThe excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients.MethodsIn 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level, and total dose of nonsteroidal antiinflammatory drug (NSAID) were dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression.ResultsMultivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 (P = 0.0003; OR, 0.87; 95% CI (0.81 to 0.94)), VAS50 (P < 0.0001; OR, 0.87; 95% CI (0.80 to 0.93)); CRP50 (P = 0.0279; OR, 0.93; 95% CI (0.88 to 0.99)), and NSAID50 (P = 0.0077; OR, 0.91; 95% CI (0.85 to 0.97)), criteria. According to the three WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9%, and 26.5%; P < 0.0001), VAS50 (72.6%, 40.4%, and 16.7%; P < 0.0001); CRP50 (87.5%, 65.7%, and 38.5%; P = 0.0001), and NSAID50 (63.2%, 51.5%, and 34.6%; P = 0.06).ConclusionsThis study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics, and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response.

Bone Mineral Density Evolution After Successful Parathyroidectomy in Patients With Normocalcemic Primary Hyperparathyroidism

CONTEXT It is unclear whether bone mineral density (BMD) improves in patients with normocalcemic primary hyperparathyroidism (PHPT) after parathyroidectomy (PTX). OBJECTIVE The objective of the study was to evaluate and compare the impact of PTX on BMD change at 1 year in normocalcemic vs hypercalcemic PHPT. DESIGN This was a longitudinal cohort study. SETTING The study took place at a referral center. PATIENTS We included 60 PHPT patients (mean age 64.0 ± 10.1 years), successfully treated by PTX by the same surgeon. Two groups were individualized according to baseline serum total (albumin corrected) calcium: 39 patients with normal baseline serum total calcium (normocalcemic group) and 21 patients with hypercalcemia at baseline (hypercalcemic group). MAIN OUTCOME MEASURE BMD changes 1 year after PTX were measured. RESULTS In the normocalcemic group, BMD increased significantly by +2.3 ± 5.0% at the spine (P = .016) and +1.9 ± 5.7% at the hip (P = .048). In the hypercalcemic group, BMD increased significantly by +4.0 ± 3.8% at the spine (P = .0003) and +3.2 ± 4.2% at the hip (P = .003). There was no difference in these BMD gains between both groups (P > .1). The presence of multiple adenomas or hyperplasia was more frequent in the normocalcemic group than in the hypercalcemic group (P = .04). CONCLUSION Our results indicate for the first time that successful PTX in normocalcemic PHPT patients with osteoporosis is followed with mild but significant BMD improvement at the spine and hip at 1 year, comparable with that observed in hypercalcemic PHPT, suggesting that PTX may be beneficial in normocalcemic PHPT.

Increased risk of osteoporosis and fracture in women with systemic sclerosis: A comparative study with rheumatoid arthritis

To investigate whether women with systemic sclerosis (SSc) have an increased risk of osteoporosis (OP) and related fractures compared to a high‐risk population with rheumatoid arthritis (RA) and also healthy controls, and to determine putative specific OP and fracture risk factors.

Safety of rituximab in rheumatoid arthritis: A long-term prospective single-center study of gammaglobulin concentrations and infections

OBJECTIVE Rituximab seems well tolerated in patients with rheumatoid arthritis (RA). However, variations in the gammaglobulin profile that might increase the infection risk have been reported. Here, our objective was to evaluate gammaglobulin concentrations and the infection risk in patients receiving rituximab therapy for RA in everyday practice. METHODS Prospective single-center observational study of 65 patients with refractory RA (median age, 59 years; range, 26-83) treated with rituximab 1 g twice 15 days apart, with or without a further 1-g dose at least 6 months later depending on the clinical response. Gammaglobulins were assayed before each rituximab dose. RESULTS The median cumulative rituximab dose was 4 g (1-16) and the median time to retreatment was 8 months (6-16). Rituximab therapy significantly improved the DAS-28 score. The gammaglobulin concentration decreased significantly between the first and last rituximab dose (from 11.6 g/L [5-26] to 8.2 g/L [3-20], a -2.6 g/L difference; P<0.05). The decrease was larger in the 24 patients with cumulative rituximab doses greater than 5 g than in the 41 other patients (difference of -4 vs. -2.7 g/L; P<0.05). Three patients experienced severe infections, two in the high-dose group and one in the other group (P=0.5). CONCLUSION These data obtained in everyday practice constitute further evidence that rituximab is well-tolerated in patients with RA. Rituximab therapy was associated with a decrease in gammaglobulin concentrations that was greater in patients receiving higher cumulative doses.

Rheumatic and musculoskeletal features of Whipple disease: a report of 29 cases.

Objective. Whipple disease is a rare infection caused by Tropheryma whipplei. Although patients commonly complain of osteoarticular involvement, musculoskeletal manifestations have been poorly described. We report cases of Whipple disease with rheumatic symptoms and describe their clinical presentation, modes of diagnosis, and outcomes. Methods. This retrospective multicenter study included patients with Whipple disease diagnosed and referenced between 1977 and 2011 in 10 rheumatology centers in France and Italy. Results. Twenty-nine patients were included. The median age was 55 years. The median time to diagnosis from first symptoms was 5 years. Polyarthritis was the most frequent presentation (20/29), and was most often chronic, intermittent (19/29), seronegative (22/23), and nonerosive (22/29). In all cases, the symptoms had led to incorrect diagnosis of inflammatory rheumatic disease and immunosuppressants, including biotherapy, were prescribed in most cases (24/29) without success. The diagnosis of Whipple disease was made by histological analysis, molecular biology tests, or both in 21%, 36%, and 43% of the cases, respectively. Duodenal biopsies were performed in most cases (86%). Synovial biopsies were performed in 18% of cases, but all contributed to diagnosis. The clinical outcomes after antibiotic therapy were good for all patients. Conclusion. Polyarthritis is the main feature observed in cases of Whipple disease; it is seronegative and associated with general and gastrointestinal symptoms. The molecular analysis of duodenal tissue and/or other tissues remains the method of choice to confirm the diagnosis. Reducing the time to diagnosis is important because severe late systemic and fatal forms of the disease may occur.

Incomplete thymic involution in systemic sclerosis and rheumatoid arthritis.

OBJECTIVE The thymus plays a crucial role in immune system homeostasis. Thymic abnormalities have been reported in many autoimmune diseases, but data for systemic sclerosis (SSc) and rheumatoid arthritis (RA) are sparse. The aim of this study was to evaluate the prevalence and correlates of radiological incomplete involution of the thymus in SSc and RA patients, and in a non-autoimmune group of controls. METHODS All patients were at least 40 years old: 96 SSc patients (median age 59 years, 80% women) and 65 RA patients (median age 57 years, 88% women) were compared with 32 control individuals (median age 63 years, 62% women). Pulmonary CT-scans performed for lung assessment were available for all individuals. For the purpose of our study, complete involution of the thymus was defined as the absence of a residual thymus or a gland thickness, corresponding to the short axis on the axial slice, of less than 7 mm. We defined incomplete involution of the thymus as a residual thymic tissue more than 7 mm thick. RESULTS The frequency of incomplete thymus involution was significantly higher in SSc and RA patients (respectively 15 and 14%) than in the control group (0%; P<0.05). Incomplete thymus involution was associated with pulmonary restrictive syndrome in SSc patients, and with biotherapy and an absence of antinuclear antibodies in RA patients. CONCLUSION Our findings show that two autoimmune diseases, SSc and RA, are associated with incomplete thymus involution.

Small, medium but not large arteries are involved in digital ulcers associated with systemic sclerosis

OBJECTIVE Digital ulcers (DU) are a burden in systemic sclerosis (SSc). Microangiopathy is a cardinal feature of SSc that plays a critical role in the development of DU. However, whether injury of medium or large vessels also contributes to DU in SSc remains controversial. METHODS To measure concomitantly in SSc patients with and without active DU: (i) the Augmentation Index of the reflected wave (Aix_75) by radial applanation tonometry, an index of small and medium arterial function; (II) the aortic pulse wave velocity (PWV), a marker of large vessel injury (aortic stiffness). RESULTS Sixty-three consecutive SSc patients were included (49 females, aged 60 [49-65] years, disease duration of 8.5 [5-13] years), including 10 (15.9%) with active DU. Patients with active DU versus those without had increased Aix_75 (35% [28-38] versus 28% [20-34], P=0.041) whereas no difference existed in PWV (7.0m/s [6.7-10.1] versus 7.6m/s [6.8-8.7], P=0.887), in systolic, diastolic, as well as aortic pulse pressure (P=0.126, 0.592, and 0.161, respectively). When compared to patients in the low tertile, patients having Aix_75 in the highest tertile had 10-fold more DU (OR=10.23; 95% CI 1.12 to 93.34, P=0.039). CONCLUSION The presence of DU is associated with increased Aix_75 whereas there is no relation with PWV. These data suggest that small and medium arteries are involved in the occurrence of DU whether large vessel stiffness does not contribute. Whether Aix_75 is predictive of further DU remained to be studied.

0232 : Small, medium but not large arteries are involved in digital ulcers associated with systemic sclerosis

Background Digital ulcers (DU) are a burden in systemic sclerosis (SSc). Microangiopathy is a cardinal feature of SSc that plays a critical role in the development of DU. However, whether injury of medium or large vessels also contributes to DU in SSc is unknown. Methods To measure concomitantly in SSc patients with and without active DU i) the Augmentation Index of the reflected wave (Aix_75) by radial applanation tonometry, an index of small and medium arterial function, II) the aortic pulse wave velocity (PWV), a marker of large vessel injury (aortic stiffness). Results 63 consecutive SSc patients were included (49 females, aged 57±12 years, disease duration 9.7±7.1 years), including 10 (15.9%) with active DU. Patients with active DU versus those without had increased Aix_75 (35% [28-38] versus 28% [20-34], p=0.041) whereas no difference existed in PWV (7,0m/s [6.7-10.1] versus 7,6m/s [6.8-8.7], p=0.887), in systolic, diastolic, as well as aortic pulse pressure (p=0.126, 0.592, and 0.161 respectively). By multivariate analysis, DU remained independently associated with Aix_75 (p=0.020). Using Aix_75 as a longitudinal variable, and when compared to patients in the low tertile, patients having Aix_75 in the highest tertile had ten-fold more DU (OR=10.23; 95% CI 1.12 to 93.34, p=0.039). Conclusion The presence of DU is independently associated with Aix_75 whereas there is no relation with PWV. These data suggest that small and medium arteries are involved in the occurrence of DU whether large vessel stiffness does not contribute. Whether Aix_75 is predictive of further DU remained to be studied.

FRI0259 Increased risk of osteoporosis and fracture in women with systemic sclerosis: A comparative study to rheumatoid arthritis and healthy controls

Objectives To investigate whether women with SSc have increased risk of OP and fractures compared to a “high risk” population with rheumatoid arthritis (RA) and also healthy controls. Methods Cross-sectional study with successive inclusion of age-matched healthy, SSc, and RA women on a 18-month period. Risk factors for OP and fractures, including age, menopausal status, calcium/vitamin D intake, family history, comorbidity and steroid use, were collected for all patients. Bone mineral density (BMD) was assessed at AP lumbar spine (L1-L4), femoral neck, and total hip region with DXA Prodigy (GE-Lunar) or QDR4500 (Hologic). We included 71 women with SSc (62±12 years old), 139 with RA (61±11 years old) and 227 healthy controls (60±8 years old). The mean ± standard deviation, SD, disease duration of SSc and RA patients was 10±9 and 18±13 years respectively (p<0.001). SSc and RA patients were more likely to receive vitamin D (69% and 76% vs. 25%, p<0.001 for both comparisons) and calcium (48% and 72% vs. 14%, p<0.001 for both comparisons) supplementation than healthy controls. RA Patients were more likely to receive calcium supplementation (100 (72%) vs. 34 (48%), p<0.001) and corticosteroids (129 (93%) vs. 41 (58%), p<0.001) than SSc patients. Cumulative dose of corticosteroids and CRP were significantly higher in patients with RA than SSc (39554±29661 mg vs.19392±19333 mg, p<0.0001 and 12±16 mg/l vs. 7±7.9 mg/l, p=0.01). Results The point prevalence of OP (T-score <-2.5) was similar in SSc and RA (30% and 32% respectively), and was for both significantly higher than in healthy controls (11%, p<0.001 vs. SSc and RA). The frequency of lumbar spine and total hip OP did not differ between SSc and RA. The point prevalence of fractures was 35% and 33% in SSc and RA, respectively (p=NS) and 10% in healthy controls (p<0.001 vs. SSc and RA). The frequency of vertebral (25% and 19%) and non-vertebral fracture (23% and 22%) did not differ between SSc and RA. Multivariate analysis identified disease duration as the only risk factor of OP in SSc (odds ratio, OR: 1.21, 95% confidence interval, CI: 1.02-1.30). There was no association between OP and corticosteroid intake, cumulative dose of corticosteroids, systemic inflammation (CRP >10mg/l) or any SSc feature Age (OR: 1.21, 95% CI 1.03-1.38) and low 25(OH)D levels (OR: 6.02, 95% CI 1.46-24.78) were recognized as risk factors of fracture in SSc. In comparison, age (OR: 1.12, 95% CI 1.02-1.26) and corticosteroid treatment (OR: 3.21, 95% CI: 1.12-10.44) were independently associated with OP in RA. Cumulative dose of corticosteroids negatively correlated with BMD measured at lumbar spine (r=0.38, p=0.01) and total hip (r=0.49, p=0.008) in RA patients. Multivariate analysis confirmed age (OR: 1.09, 95% CI 1.03-1.18), OP (OR: 3.22, 95% CI 1.18-8.75) and low 25(OH)D levels (OR: 4.31, 95% CI 1.29-14.41) as independent risk factors of fractures in RA. Conclusions The prevalence of OP and fracture in SSc was increased compared to healthy women and reached the high prevalence associated with RA. Age and vitamin D deficiency were identified as risk factors of fracture in SSc. Thus, increasing the awareness and performance of BMD measurements together with vitamin D supply in patients with SSc is warranted. Disclosure of Interest None Declared