Body mass index influences the response to infliximab in ankylosing spondylitis

INTRODUCTION: The 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. METHODS: In 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. RESULTS: Multivariate 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). CONCLUSIONS: This 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

Etanercept treatment for extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, or psoriatic arthritis

To describe the 6-year safety and efficacy of etanercept (ETN) in children with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA) METHODS: Patients who completed the 2-year, open-label, phase III CLinical Study In Pediatric Patients of Etanercept for Treatment of ERA, PsA, and Extended Oligoarthritis (CLIPPER) were allowed to enroll in its 8-year long-term extension (CLIPPER2). Children received ETN at a once-weekly dose of 0.8 mg/kg, up to a maximum dose of 50 mg/week. Efficacy assessments included the JIA core set of outcomes, the JIA American College of Rheumatology response criteria (JIA-ACR), and the Juvenile Arthritis Disease Activity Score (JADAS). Efficacy data are reported as responder analyses using a hybrid method for missing data imputation and as observed cases. Safety assessments included treatment-emergent adverse events (TEAEs).Out of 127 patients originally enrolled in CLIPPER, 109 (86%) entered CLIPPER2. After 6 years of trial participation (2 years in CLIPPER and 4 years in CLIPPER2), 41 (32%) patients were still taking ETN, 13 (11%) entered the treatment withdrawal phase after achieving low/inactive disease (of whom 7 had to restart ETN), 36 (28%) discontinued treatment for other reasons but are still being observed, and 37 (29%) discontinued treatment permanently. According to the hybrid imputation analysis, proportions of patients achieving JIA ACR90, JIA ACR100, and JADAS inactive disease after the initial 2 years of treatment were 58%, 48%, and 32%, respectively. After the additional 4 years, those proportions in patients who remained in the trial were 46%, 35%, and 24%. Most frequently reported TEAEs [n (%), events per 100 patient-years] were headache [28 (22%), 5.3], arthralgia [24 (19%), 4.6], and pyrexia [20 (16%), 3.8]. Number and frequency of TEAEs, excluding infections and injection site reactions, decreased over the 6-year period from 193 and 173.8, respectively, during year 1 to 37 and 61.3 during year 6. A single case of malignancy (Hodgkin's lymphoma) and no cases of active tuberculosis, demyelinating disorders, or deaths were reported.Open-label etanercept treatment for up to 6 years was safe, well tolerated, and effective in patients with eoJIA, ERA, and PsA.ClinicalTrials.gov: CLIPPER, NCT00962741 , registered 20 August, 2009, CLIPPER2, NCT01421069 , registered 22 August, 2011

Long‐term safety, efficacy, and quality of life in patients with juvenile idiopathic arthritis treated with intravenous abatacept for up to seven years

ClinicalTrials.gov identifier: NCT00095173[Abstract] Objective. The efficacy and safety of abatacept in patients with juvenile idiopathic arthritis (JIA) who experienced an inadequate response to disease‐modifying antirheumatic drugs were previously established in a phase III study that included a 4‐month open‐label lead‐in period, a 6‐month double‐blind withdrawal period, and a long‐term extension (LTE) phase. The aim of this study was to present the safety, efficacy, and patient‐reported outcomes of abatacept treatment (10 mg/kg every 4 weeks) during the LTE phase, for up to 7 years of followup. Methods. Patients enrolled in the phase III trial could enter the open‐label LTE phase if they had not achieved a response to treatment at month 4 or if they had received abatacept or placebo during the double‐blind period. Results. One hundred fifty‐three (80.5%) of 190 patients entered the LTE phase, and 69 patients (36.3%) completed it. The overall incidence rate (events per 100 patient‐years) of adverse events decreased during the LTE phase (433.61 events during the short‐term phase [combined lead‐in and double‐blind periods] versus 132.39 events during the LTE phase). Similar results were observed for serious adverse events (6.82 versus 5.60), serious infections (1.13 versus 1.72), malignancies (1.12 versus 0), and autoimmune events (2.26 versus 1.18). American College of Rheumatology (ACR) Pediatric 30 (Pedi 30) responses, Pedi 70 responses, and clinically inactive disease status were maintained throughout the LTE phase in patients who continued to receive therapy. Improvements in the Child Health Questionnaire physical and psychosocial summary scores were maintained over time. Conclusion. Long‐term abatacept treatment for up to 7 years was associated with consistent safety, sustained efficacy, and quality‐of‐life benefits in patients with JIA

Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study

OBJECTIVE: To investigate the efficacy and safety of etanercept (ETN) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). METHODS: CLIPPER is an ongoing, Phase 3b, open-label, multicentre study; the 12-week (Part 1) data are reported here. Subjects with eoJIA (2-17 years), ERA (12-17 years), or PsA (12-17 years) received ETN 0.8 mg/kg once weekly (maximum 50 mg). Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology (ACR) 30 criteria at week 12; secondary outcomes included JIA ACR 50/70/90 and inactive disease. RESULTS: 122/127 (96.1%) subjects completed the study (mean age 11.7 years). JIA ACR 30 (95% CI) was achieved by 88.6% (81.6% to 93.6%) of subjects overall; 89.7% (78.8% to 96.1%) with eoJIA, 83.3% (67.2% to 93.6%) with ERA and 93.1% (77.2% to 99.2%) with PsA. For eoJIA, ERA, or PsA categories, the ORs of ETN vs the historical placebo data were 26.2, 15.1 and 40.7, respectively. Overall JIA ACR 50, 70, 90 and inactive disease were achieved by 81.1, 61.5, 29.8 and 12.1%, respectively. Treatment-emergent adverse events (AEs), infections, and serious AEs, were reported in 45 (35.4%), 58 (45.7%), and 4 (3.1%), subjects, respectively. Serious AEs were one case each of abdominal pain, bronchopneumonia, gastroenteritis and pyelocystitis. One subject reported herpes zoster and another varicella. No differences in safety were observed across the JIA categories. CONCLUSIONS: ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA, ERA and PsA, with no unexpected safety findings

Traitement par lavage articulaire des arthrites récidivantes du genou chez l'enfant

PARIS5-BU Méd.Cochin (751142101) / SudocPARIS-BIUM (751062103) / SudocCentre Technique Livre Ens. Sup. (774682301) / SudocSudocFranceF

Etude rétrospective d une cohorte d arthrites juvéniles idiopathiques traitées par anti TNF alpha

L arthrite juvénile idiopathique (AJI) est le rhumatisme inflammatoire le plus fréquent chez l enfant. Cette pathologie est classifiée en différentes formes selon le nombre d articulations atteintes, la présence ou non de signes généraux et de symptômes associés. Les symptômes articulaires et oculaires sont parfois responsables d un handicap important mais la gravité de cette pathologie est également imputable à ses complications telles que l ostéoporose, le retard de croissance ou plus rarement le syndrome d activation macrophagique ou l amylose, ou à des complications secondaires aux traitements. L observation de taux sériques et articulaires particulièrement élevés de la cytokine TNF alpha chez les enfants atteints d AJI, a amené à utiliser les inhibiteurs des anti TNF alpha chez les enfants réfractaires aux traitements usuels depuis 2000. Trois anti TNF sont actuellement disponibles : l etanercept, l infliximab et l adalimumab. Deux études sont décrites dans cet ouvrage. La première concerne une cohorte de 65 patients traités par anti TNF alpha afin d évaluer dans la durée le traitement par anti TNF. Cette étude s étend sur 9 ans. Les traitements par anti TNF alpha confirment leur efficacité dans la durée à la fois sur les symptômes articulaires et sur le syndrome inflammatoire biologique. Celle-ci est plus importante dans les spondylarthropathies et moindre dans les formes systémiques que dans les autres sous-types d AJI. La deuxième étude s intéresse aux traitements par anti TNF alpha dans les uvéites associées aux AJI et confirme l efficacité de ces molécules sur les symptômes oculaires.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Glucocorticoid-sparing effect of first-year anti-TNFα treatment in rheumatoid arthritis (CORPUS Cohort).

International audienceAnti-TNFα agents are indicated in selected patients with rheumatoid arthritis (RA) who respond inadequately to methotrexate and particularly when glucocorticoids are mandatory. We evaluated whether a glucocorticoid-sparing effect occurred during the first year of anti-TNF-α therapy.Between 2007 and 2009, the French multicentre, longitudinal, prospective, observational, population-based CORPUS cohort included biologic-naive patients with inflammatory joint disease. Patients with active RA treated with glucocorticoids were included. Patients who received at least one anti-TNFα injection during follow-up were compared to anti-TNF-α non-users.Among the 205 patients, 76.1% were women, mean disease duration was 7.7±8.3 years, mean DAS28 was 5.2±1.3, mean follow-up was 13.1±2.8 months, and mean prednisone dose was 9.9±9.6 mg/day. The 75 (36.6%) anti-TNF-α recipients were younger, had a longer RA duration, more often tested positive for rheumatoid factor and anti-citrullinated peptide antibody, more often received previous DMARDs, received a higher methotrexate dosage, had fewer intra-articular glucocorticoid injections at baseline and were more often followed by hospital practitioners than non-recipients. Mean prednisone dosage decreased from 11.8±12.7 to 5.9±9.7 mg/day in recipients and from 8.7±7.1 to 5.0±4.4 mg/day in non-recipients. Prednisone was stopped more often among recipients (21/59, 35.6%) than among non-recipients (16/94, 17.0%) (p=0.01). By multivariate analysis, factors independently associated with lower prednisone requirements were baseline daily prednisone dosage, a CRP >10 mg/l and not to be followed by an office-based practitioner.This study showed a significantly higher glucocorticoid discontinuation rate among anti-TNF-α recipients than among non-recipients. However, the glucocorticoid-sparing effect was small and not observed by multivariate analysis

Glucocorticoid-sparing effect of first-year anti-TNFα treatment in rheumatoid arthritis (CORPUS Cohort).

International audienceAnti-TNFα agents are indicated in selected patients with rheumatoid arthritis (RA) who respond inadequately to methotrexate and particularly when glucocorticoids are mandatory. We evaluated whether a glucocorticoid-sparing effect occurred during the first year of anti-TNF-α therapy.Between 2007 and 2009, the French multicentre, longitudinal, prospective, observational, population-based CORPUS cohort included biologic-naive patients with inflammatory joint disease. Patients with active RA treated with glucocorticoids were included. Patients who received at least one anti-TNFα injection during follow-up were compared to anti-TNF-α non-users.Among the 205 patients, 76.1% were women, mean disease duration was 7.7±8.3 years, mean DAS28 was 5.2±1.3, mean follow-up was 13.1±2.8 months, and mean prednisone dose was 9.9±9.6 mg/day. The 75 (36.6%) anti-TNF-α recipients were younger, had a longer RA duration, more often tested positive for rheumatoid factor and anti-citrullinated peptide antibody, more often received previous DMARDs, received a higher methotrexate dosage, had fewer intra-articular glucocorticoid injections at baseline and were more often followed by hospital practitioners than non-recipients. Mean prednisone dosage decreased from 11.8±12.7 to 5.9±9.7 mg/day in recipients and from 8.7±7.1 to 5.0±4.4 mg/day in non-recipients. Prednisone was stopped more often among recipients (21/59, 35.6%) than among non-recipients (16/94, 17.0%) (p=0.01). By multivariate analysis, factors independently associated with lower prednisone requirements were baseline daily prednisone dosage, a CRP >10 mg/l and not to be followed by an office-based practitioner.This study showed a significantly higher glucocorticoid discontinuation rate among anti-TNF-α recipients than among non-recipients. However, the glucocorticoid-sparing effect was small and not observed by multivariate analysis

Serious adverse events in children with juvenile idiopathic arthritis and other rheumatic diseases on tocilizumab - a real-world experience

OBJECTIVES: To assess the incidence rate and type of serious adverse events (SAE) in children with rheumatic inflammatory diseases treated with the interleukin 6 blocker tocilizumab (TCZ). METHODS: A retrospective review of all consecutive patients diagnosed with an inflammatory rheumatic disease and receiving at least one dose of TCZ was performed in two French tertiary pediatric rheumatology centers between 01/2007 and 06/2019. SAE were defined as a life-threatening event and/or an event requiring hospital admission, leading to permanent disability or treatment discontinuation. RESULTS: One hundred four children (64 female) were included. Most children suffered from systemic (n = 43) or polyarticular-course juvenile idiopathic arthritis (n = 43). Median age at TCZ start was 8.9 years (IQR 4.7 - 12.1), most children had received prednisone (81%), and/or a biologic agent (84%) prior to TCZ. Median TCZ treatment duration was 1.6 years (IQR 0.5 - 2.7), total TCZ exposure 215 patient years. Thirty-three SAE were observed in 26 (25%) children (SAE 15.3/100 patient years), mostly infections and infusion reactions. Children with SAE were significantly younger at disease onset (p = 0.034) and TCZ initiation (p = 0.016). Children experiencing infusion reactions were more likely to have systemic JIA or another autoinflammatory disease (p = 0.021), they all had active disease. At last follow up, 61 (59%) children remained on TCZ. CONCLUSION: In this cohort, SAE and most commonly serious infections were observed in a quarter of children. Severe infusion reactions were associated with persistently active autoinflammatory disease. Ongoing careful monitoring of TCZ-treated patients, especially young children with marked systemic inflammation is required.status: publishe