P. Gaudin

Positivity for anti-cyclic citrullinated peptide is associated with a better response to abatacept: data from the ‘Orencia and Rheumatoid Arthritis’ registry

Objectives Very limited data are available regarding the efficacy of abatacept (ABA) in real life. The aims of this study were to determine the efficacy of ABA in rheumatoid arthritis and predicting factors of efficacy in common practice. Methods The Orencia and Rheumatoid Arthritis” (ORA) prospective registry, promoted by the French Society of Rheumatology, has included 1003 patients with RA. Results 773 patients had already fulfilled the 6-month follow-up visit. Only 21.3% of patients would have fulfilled inclusion criteria used in pivotal controlled trials. The European League Against Rheumatism (EULAR) response, was observed in 330 (59.1%) of the 558 assessed patients (good response: 20.4%, moderate response: 38.7%) and was similar in patients who did and in patients who did not fulfill inclusion criteria of controlled trials. Among EULAR responders, initial 28-joint disease activity score (5.4 (4.7-6.5) in responders vs 4.9 (4.0-6.0) in non responders, p< 0.0001), the proportion of rheumatoid factor (75.6% vs 66.7%, p= 0.03) and the proportion of anti-cyclic citrullinated peptide antibody (anti-CCP)-positivity (75.9% vs 62.2%, p= 0.001) were significantly higher. In multivariate analysis adjusted on initial 28-joint disease activity score and CRP, anti-CCP positivity was associated with EULAR response (OR=1.9;95% CI=1.2 to 2.9, p=0.007), but not rheumatoid factor (OR=1.0;95% CI=0.6 to 1.6, p=0.9). Anti-CCP positivity was also significantly associated with a higher ABA retention rate at 6 months. Conclusions Real life efficacy of ABA in the ORA registry was similar as that reported in clinical trials. Anti-CCP positivity was associated with a better response to ABA, independently from disease activity.

Efficacy of resistance exercises in rheumatoid arthritis: meta-analysis of randomized controlled trials

OBJECTIVEnTo evaluate the efficacy of resistance exercises in RA patients.nnnMETHODSnA systematic literature search was done using Pubmed, Embase and Cochrane databases through November 2009 and in abstracts presented at rheumatology scientific meetings over the past 3 years. Randomized controlled trials (RCTs) comparing resistance exercise based therapy with interventions without resistance exercise for the treatment of RA patients were included. Outcomes studied were post-intervention disability on the HAQ, functional capacity assessed by walking speed, pain on the visual analogue scale (VAS), joint count, isometric, isokinetic and grip strength. Efficacy was assessed by weighted mean differences (WMDs) and tolerance was assessed by relative risk (RR). Data were pooled using the inverse of variance model, and heterogeneity was tested.nnnRESULTSnTen RCTs, including 547 patients, met the study inclusion criteria. The mean (S.D.) Jadad score was 2.3 (0.6). Resistance exercises significantly improved isokinetic strength (WMDu2009=u200923.7%, Pu2009<u20090.001), isometric strength (WMDu2009=u200935.8%, Pu2009<u20090.001), grip strength (WMDu2009=u200926.4%, Pu2009<u20090.001) and HAQ (WMDu2009=u2009-0.22, Pu2009<u20090.001). Exercise also had a positive impact on the 50-foot walking test (WMDu2009=u2009-1.90u2009s, Pu2009<u20090.001) and ESR (WMDu2009=u2009-5.17, Pu2009=u20090.005). Withdrawals [RRu2009=u20090.95, 95% confidence interval (CI) 0.61, 1.48] and adverse events (RRu2009=u20091.08, 95% CI 0.72, 1.63) were well balanced in both groups. Patient and exercise characteristics did not influence the results. Subgroup analysis revealed a trend towards higher efficacy associated with high-intensity programmes.nnnCONCLUSIONnResistance exercise in RA is safe, and the improvement in most outcomes was statistically significant and possibly clinically relevant for RA disability.

Masitinib in the treatment of active rheumatoid arthritis: results of a multicentre, open-label, dose-ranging, phase 2a study

IntroductionSince current treatment options for patients suffering from active rheumatoid arthritis (RA) remain inadequate, especially for those unresponsive to disease-modifying antirheumatic drugs (DMARDs), new and improved medication is needed. This study evaluates the safety and efficacy of masitinib (AB1010), a potent and selective protein tyrosine kinase inhibitor of c-KIT, in the monotherapy treatment of DMARD-refractory RA.MethodsThis was a multicentre, uncontrolled, open-label, randomised, dose-ranging, phase 2a trial. Masitinib was administered orally to 43 patients who had inadequate response to DMARDs, at initial randomised dosing levels of 3 and 6 mg/kg per day over a 12-week period. Dose adjustment was permitted based upon tolerability and response criteria. Efficacy was assessed via American College of Rheumatology 20%/50%/70% improvement criteria (ACR20/50/70) responses, disease activity score using 28 joint counts (DAS28), index of improvement in RA (ACRn) and C-reactive protein (CRP) improvement, relative to baseline at week 12.ResultsImprovement was observed in all efficacy endpoints, including ACR20/50/70 scores of 54%, 26% and 8%, respectively, and a reduction in CRP level by greater than 50% for approximately half the population. This improvement was sustainable throughout an extension phase (> 84 weeks) and was also independent of initial DMARD resistance (anti-tumour necrosis factor-alpha and/or methotrexate). A relatively high patient withdrawal rate (37%) required the use of last observation carried forward (LOCF) data imputation. Incidence of adverse events was high (95%), although the majority were of mild or moderate severity with a considerable decline in frequency observed after 12 weeks of treatment. Two nonfatal serious adverse events were reported. Dose-response analyses tentatively indicate that an initial dosing level of 6.0 mg/kg per day administered orally in two daily intakes is the most appropriate, based upon potency and tolerability trends.ConclusionsTreatment with masitinib improved DMARD-refractory active RA. Following an initial high incidence of mostly mild to moderate side effects during the first 12 weeks of treatment, masitinib appears to be generally well tolerated. This, together with evidence of a sustainable efficacy response, suggests that masitinib is suitable for long-term treatment regimens. Since this was the first study of masitinib in a nononcologic pathology, the relatively high patient withdrawal rate observed can be partly attributed to a highly cautious response to adverse events. There is sufficient compelling evidence to warrant further placebo-controlled investigation.Trial registrationClinicalTrials.gov NCT00831922.

Intervertebral disk degeneration and herniation: the role of metalloproteinases and cytokines.

This article reviews the role of metabolic factors, including metalloproteinases and cytokines, in the occurrence of degenerative disk disease and disk herniation. Given that mechanical factors alone cannot cause disk degeneration, studies must explore metabolic, genetic, nutritional, and age-related factors. Zinc metalloproteinases exert particularly important effects, not only directly, but also indirectly through promotion of neovascularization. The production of these enzymes is dependent on a number of cytokines and on the cell changes they induce. This complex effect acts both on disk matrix degeneration and on the pain generated by contact between the protruding disk and the nerve roots. However, it can have a favorable effect by promoting resorption of the herniated disk. Available data on the role for mechanical factors on the disk chondrocyte metabolism and on metalloproteinase production show that mechanical and metabolic factors interact closely to produce disk disorders.

Predictive risk factors of serious infections in patients with rheumatoid arthritis treated with abatacept in common practice: results from the Orencia and Rheumatoid Arthritis (ORA) registry

Objectives Little data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry. Methods ORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA. At baseline, 3 months, 6u2005months and every 6u2005months or at disease relapse, during 5u2005years, standardised information is prospectively collected by trained clinical nurses. A serious infection was defined as an infection occurring during treatment with ABA or during the 3u2005months following withdrawal of ABA without any initiation of a new biologic and requiring hospitalisation and/or intravenous antibiotics and/or resulting in death. Results Baseline characteristics and comorbidities: among the 976 patients included with a follow-up of at least 3u2005months (total follow-up of 1903 patient-years), 78 serious infections occurred in 69 patients (4.1/100 patient-years). Predicting factors of serious infections: on univariate analysis, an older age, history of previous serious or recurrent infections, diabetes and a lower number of previous anti-tumour necrosis factor were associated with a higher risk of serious infections. On multivariate analysis, only age (HR per 10-year increase 1.44, 95% CI 1.17 to 1.76, p=0.001) and history of previous serious or recurrent infections (HR 1.94, 95% CI 1.18 to 3.20, p=0.009) were significantly associated with a higher risk of serious infections. Conclusions In common practice, patients treated with ABA had more comorbidities than in clinical trials and serious infections were slightly more frequently observed. In the ORA registry, predictive risk factors of serious infections include age and history of serious infections.

Risk of postoperative infections and the discontinuation of TNF inhibitors in patients with rheumatoid arthritis: A meta-analysis.

OBJECTIVEnTo determine whether continuation of tumor necrosis factor inhibitors (TNFi) before surgery increases the risk of surgical site infection (SSI) in rheumatoid arthritis (RA) patients.nnnMETHODSnA systematic review of the literature was conducted from January 2000 to May first 2014, using the databases of PubMed, Cochrane review, Embase, and manual research of abstracts presented in scientific congresses. Most included studies were retrospective. We compared the risk of SSI in the case of discontinuation of TNFi versus continuing TNFi treatment before a surgery.nnnRESULTSnSix studies, with a total of 2743xa0patients (1360 in the group continuing TNFi agent and 1383 in the group discontinuing TNFi) were included. There was a decreased risk of SSI in patients stopping TNFi (relative risk [RR]=0.62 [95% confidence interval [CI] 0.43-0.89], P=0.99, I2=0%). Concerning overall complications, there was also a decreased risk in patients discontinuing TNFi treatment (RR=0.60 [95% CI 0.42-0.87], P=0.26, I2=25%).nnnCONCLUSIONnThis meta-analysis showed an increased risk of SSI in patients under TNF inhibitor, and a decreased risk of SSI in case of interruption of treatment during the perioperative time.

Differences in MMPs and TIMP-1 expression between intervertebral disc and disc herniation.

Joint Bone Spine - In Press.Proof corrected by the author Available online since lundi 8 octobre 2012

OP0303 Systematic screening of comorbidities improves vaccination rates, skin cancer screening and vitamin d supplementation in patients with axial spondyloarthritis: results of the comedspa prospective, controlled, one year randomised trial

Background Specific recommendations for the detection/prevention of comorbidities have been proposed for patients with SpA. However, we know that often a gap exists between recommendation and their implementation in daily practice Objectives To evaluate the impact of a program of systematic screening of comorbidities and its management (detection/prevention). Methods Prospective, randomised controlled open, 12u2009month trial (NCT02374749). Patients: Axial SpA (according to rheumatologist). Study treatment: Collection of data by the nurse during a specific out-patient visit for the 5 studied SpA comorbidities (i.e. cardiovascular disease (CVD), osteoporosis, cancer, infection and peptic ulcer) according to the recommendations of the French Society of Rheumatology. In the event of non-agreement with the recommendation the patient was informed. A report summarising the results of this program prepared by the nurse was sent to the patient’s attending physician and rheumatologist. Treatment allocation: After written informed consent, the study treatment was allocated randomly. Outcome variables: the main outcome was the change after one year of a comorbidity score. This weighted composite comorbidity score ranged from 0 to 100, where 0=optimalu2009management of the 5 studied comorbidities and its weights were derived from the percentage of attributed mortality in SpA to each comorbidity in the literature, i.e. 40 points for CV disease, 20 points for cancer and infection, 10 points for osteoporosis and 10 points for peptic ulcer. The number of patients with actions undertaken against comorbidities according to the recommendations during the 12 months following this program were defined as secondary variables Results There were no differences in the baseline characteristics of the 502 recruited patients (252 and 250 in the active and control groups, respectively): Age: 46.7±12.2 years, male gender: 62.7%, disease duration: 13.7±11.0u2009y, Xray sacroiliitis 62.8%, MRI sacroiliitis 65.7%, current biologic treatment: 78.3%, ASDAS-CRP: 1.9±0.8, BASFI: 25.6±22.3. During the 1u2009year follow-up period, the comorbidity score decreased more in the active group, but this difference was not significant (−3,20 vs −1.85). The number of actions per patient was statistically higher in the group comorbidities : 4.54±2.08u2009vs 2.65±1.57 (p<0.001); the number of patients with actions performed to be in agreement with recommendations during the 12u2009months follow-up was higher in the active group for infections (flu vaccination : 28.6% vs 9.9%, p<0.01; pneumococcal vaccination:40.0% vs 21.1%,p=0.04), skin cancer screening (36.3% vs 17.2%; p=0.04), and osteoporosis (BMD performed: 22.6% vs 8.7%, p<0.01; Vitamin D supplementation initiation: 51.9% vs 9.4%, p<0.01). Conclusions This study highly suggests the short-term benefit of program on the systematic screening of comorbidities for its management in agreement with recommendations, even if this young age population of axSpA patients. Acknowledgements This study was conducted thanks to a grant from the French National Research Program (PHRC) thanks to an unrestricted grant from ABBVIE. Disclosure of Interest None declared

OP0164-HPR Impact of a nurse-led program of patient self-assessment and self-management axial spondyloarthritis: results of a prospective, multicentre, randomised, controlled trial (COMEDSPA)

Background Nurses should promote self-assessment and self-management skills in order that patients might achieve a greater self efficacy and improvement in patients with axSpA. Objectives To evaluate the impact of a nurse-led program of self-management/-assessment for disease activity program in axSpA. Methods Prospective, randomised, controlled, open, 12u2009month trial (NCT02374749). Participants 1/Patients: consecutive Axial SpA patients (according to rheumatologist) attending a clinic of the participating centres were invited 0.2/Nurses :all participated at a 1u2009day meeting prior the start of the study. Study treatment: a program including: 1) Self-management=a) a video explaining the disease, the interest of smoking cessation in axial SpA, the role of NSAIDs as cornerstone treatment in axSpA in the absence of contra-indications, the interest of physical activity and exercise, followed by a discussion with the nurse; b) physical examination by the nurse to check for the presence of spinal deformitiesand depending on the absence/presence of such deformities projection of a specific video of home-based exercises. 2) Self-assessment: Video presentation of the rationale of the use of a composite index (ASDAS/BASDAI), followed by discussion with the nurse. Explanation by the nurse of the collection, calculation of BASDAI and ASDAS Treatment allocation: after written informed consent, the treatment was allocated randomly via en electronic system. Outcome variables: Primary: The level of coping (0–10, where 0=veryu2009well) after 12 months. Other variables: Successful smoking cessation, NSAID intake, Number of home-based or supervised exercise, international physical activity questionnaire (IPAQ). Results Baseline characteristics of the 502 recruited patients (250 and 252 in the active and control groups, respectively): Age: 46.7±12.2 years, male gender: 62.7%, disease duration: 13.7±11.0u2009y, Xray sacroiliitis 62.8%, MRI sacroiliitis 65.7%, current biologic treatment: 78.3%, ASDAS-CRP: 1.9±0.8, BASFI: 25.6±22.3. After 1u2009year, coping levels were lower in the active group, but not significant (2.8±2.0u2009vs 3.0±2.1, p=0.3). However, there was a significant decrease in the BASDAI in the active group (- 1.2±15.8u2009vs+1.4±15.7, p=0.03), a significant increase in the number (6.1±28.8u2009vs −0.4±26.9, p=0.03) and duration (4.3±20.1u2009vs −1.7±20.7, p<0.01) of the home-exercises in the active group, and a greater IPAQ score in the active group at the end of follow-up (138.4±227u2009vs 95.6±173,p=0.02). Conclusions This study highly suggests a short-term benefit of a nurse led program on the self-management and self-assessment for disease activity in a young axSpA population in particular with regard to the frequency and the duration of home exercises. Acknowledgements This study was conducted thanks to a grant from the French National Research Program (PHRC) thanks to an unrestricted grant from ABBVIE. Disclosure of Interest None declared

Une consommation modérée d’alcool prévient la progression radiographique chez l’homme et augmente la progression radiographique chez la femme dans la polyarthrite rhumatoïde débutante : Résultats de la cohorte ESPOIR

Introduction: We conducted this study to determine whether alcohol consumption influences radiological progression in early rheumatoid arthritis (RA). Methods: Patients fulfilling the 2010 criteria in the early arthritis cohort ESPOIR (Etude et Suivi des Polyarthrites Indifferenciees Recentes) were included in this study. Alcohol consumption was collected at baseline in grams/day (g/d) and at each visit. We classified alcohol consumption into 3 groups abstinent (0g/d); moderate ≤20g/d for women and ≤30g/d for men; and abuse >20g/d for women and >30g/d for men. The primary outcome was the occurrence of radiological progression, defined by an increase ≥5 points of the total Sharp/Van der Heijde score (SHS). We investigated whether alcohol consumption is predictive of radiological progression at 1, 3 and 5 years by univariate and multivariate analysis adjusted on age, baseline erosion, rheumatoid factors (RF), Anti-Citrullinated Peptide Antibody (ACPA) and smoking status. Results: 596 patients were included and analyzed. When considering the influence of gender on the interaction between alcohol consumption and radiological progression, we showed a deleterious effect of moderate consumption in women (OR = 1.89 [1.12; 3.17], p=0.017) and probable protective effect of moderate consumption in men (OR = 0.45 [0.19; 1.04], p=0.061) (Figure 2) in both univariate and multivariate analysis. Conclusion: Our data suggest deleterious effect of moderate consumption of alcohol on radiological progression in women but not in men with early RA.