Abatacept in difficult-to-treat juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children and an important cause of short-term and long-term disability. Gene changes in the immune system can predispose to JIA and regulation of the immune system is crucial in the pathogenesis. The goal of therapy is complete disease control using disease-modifying antirheumatic drugs (DMARDS). Activated T-cells may play a role in the immunopathology of JIA. Therefore, targeting T-cell activation is a rational approach for the treatment of JIA. Abatacept (ABA), a selective co-stimulation modulator, has been shown to be effective in treating all JIA subtypes and is generally safe and well tolerated in JIA. Neutralizing antibodies were found in 6/9 (67%) of seropositive patients, but anti-ABA antibodies did not appear to be associated with disease flare, serious adverse events, acute infusional adverse events, hypersensitivity, autoimmune disorders, or low ABA serum concentrations. Anti-ABA antibodies were more frequent when ABA concentrations were below therapeutic levels. Although information on ABA in JIA is still limited, available data suggest a potential role in difficult to treat JIA patients previously treated with other biologic agents and for non-responders to TNF-blockade

Comparison of treatment response, remission rate and drug adherence in polyarticular juvenile idiopathic arthritis patients treated with etanercept, adalimumab or tocilizumab

Background Treatment response, remission rates and compliance in patients with polyarticular juvenile idiopathic arthritis (polyJIA) treated with adalimumab, etanercept, or tocilizumab were analyzed in clinical practice. Methods Data collected in the German BIKER registry were analyzed in patients with polyJIA who started treatment with approved biologics, adalimumab, etanercept or tocilizumab, from 2011 to 2015. Baseline patient characteristics, treatment response, safety and drug survival were compared. Results Two hundred thirty- six patient started adalimumab, 419 etanercept and 74 tocilizumab, with differences in baseline patient characteristics. Baseline Juvenile Disease Activity Score (JADAS)10 (mean ± SD) in the adalimumab/etanercept/tocilizumab cohorts was 12.1+/−7.6, 13.8 ± 7.1 and 15.1 ± 7.4, respectively (adalimumab vs etanercept, p = 0.01), and Childhood Health Assessment Questionnaire (CHAQ)-disability index scores was 0.43 ± 0.58, 0.59 ± 0.6 and 0.63 ± 0.55, respectively (adalimumab vs etanercept, p < 0.001). Uveitis history was more frequent in the adalimumab cohort (OR 5.73; p < 0.001). Balanced patients’ samples were obtained by a generalized propensity score to adjust for baseline differences. Pediatric ACR30/50/70/90 criterion improvement after 3 months treatment was achieved by 68%/60%/42%/24% in the etanercept cohort, 67%/59%/43%/27% in the adalimumab cohort and 61%/52%/35%/26% in the tocilizumab cohort. At 24 months, JADAS minimal disease activity was achieved in 52.4%/61.3%/52.4% and JADAS remission in 27.9%/34.8%/27.9% patients in the adalimumab/etanercept/tocilizumab cohorts, respectively. Etanercept was used in 95.5% of patients as a first biologic, adalimumab in 50.8% and tocilizumab in 20.2%. There were no important differences in efficacy between first-line and second-line use of biologics. In total 60.4%/49.4%/31.1% patients discontinued adalimumab/etanercept/tocilizumab, respectively (HR for adalimumab 1.67; p < 0.001; HR for tocilizumab 0.35; p = 0.001). Drug survival rates did not differ significantly in patients on biologic monotherapy compared with combination therapy with methotrexate. Over 4 years observation under etanercept/adalimumab/tocilizumab, 996/386/103 adverse events, and 148/119/26 serious adverse events, respectively, were reported. Conclusions In clinical practice, etanercept is most frequently used as first-line biologic. Adalimumab/etanercept/tocilizumab showed comparable efficacy toward polyJIA. Overall, tolerance was acceptable. Interestingly, compliance was highest with tocilizumab and lowest with adalimumab. This study provides the first indication for the comparison of different biologic agents in polyarticular JIA based on observational study data with all their weaknesses and demonstrates the need for well-controlled head-to-head studies for confirmation

MRP8 and MRP14, phagocyte-specific danger signals, are sensitive biomarkers of disease activity in cryopyrin-associated periodic syndromes

To assess the sensitivity of the phagocyte-specific molecules myeloid-related protein (MRP) 8 and MRP14 (calprotectin) for monitoring disease activity during anti-interleukin (IL)-1 therapies in patients with cryopyrin-associated periodic syndromes (CAPS), including familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological, cutaneous and articular (CINCA) syndrome

Sustained remission of symptoms and improved health-related quality of life in patients with cryopyrin-associated periodic syndrome treated with canakinumab: results of a double-blind placebo-controlled randomized withdrawal study

Abstract Introduction To assess the effect of canakinumab, a fully human anti-interleukin-1β antibody, on symptoms and health-related quality of life (HRQoL) in patients with cryopyrin-associated periodic syndrome (CAPS). Methods In this 48-week, phase 3 study, patients with CAPS received canakinumab 150 mg subcutaneously at 8-week intervals. All patients (n = 35) received canakinumab during weeks 1 through 8; weeks 9 through 24 constituted a double-blind placebo-controlled withdrawal phase, and weeks 24 through 48 constituted an open-label phase in which all patients received canakinumab. Patient and physician assessments of symptoms, levels of inflammatory markers, and HRQoL were performed. Results Rapid symptom remission was achieved, with 89% of patients having no or minimal disease activity on day 8. Responses were sustained in patients receiving 8-weekly canakinumab. Responses were lost during the placebo-controlled phase in the placebo group and were regained on resuming canakinumab therapy in the open-label phase. Clinical responses were accompanied by decreases in serum levels of C-reactive protein, serum amyloid A protein, and interleukin-6. HRQoL scores at baseline were considerably below those of the general population. Improvements in all 36-item Short-Form Health Survey (SF-36) domain scores were evident by day 8. Scores approached or exceeded those of the general U.S. population by week 8 and remained stable during canakinumab therapy. Improvements in bodily pain and role-physical were particularly marked, increasing by more than 25 points from baseline to week 8. Therapy was generally well tolerated. Conclusions Canakinumab, 150 mg, 8-weekly, induced rapid and sustained remission of symptoms in patients with CAPS, accompanied by substantial improvements in HRQoL. Trial registration Clintrials.gov NCT0046598

Use of the Auto-inflammatory Disease Activity Index to monitor disease activity in patients with colchicine-resistant Familial Mediterranean Fever, Mevalonate Kinase Deficiency, and TRAPS treated with canakinumab

To evaluate the feasibility of the autoinflammatory disease activity index (AIDAI) as a tool to assess disease activity in patients with hereditary recurrent fever syndromes (HRFs) treated with canakinumab

Registries in rheumatological and musculoskeletal conditions. Paediatric Behçet's disease: an international cohort study of 110 patients. One-year follow-up data

Objective. To set-up an international cohort of patients suspected with Behçet's disease (BD). The cohort is aimed at defining an algorithm for definition of the disease in children. Methods. International experts have defined the inclusion criteria as follows: recurrent oral aphthosis (ROA) plus one of following—genital ulceration, erythema nodosum, folliculitis, pustulous/acneiform lesions, positive pathergy test, uveitis, venous/arterial thrombosis and family history of BD. Onset of disease is <16 years, disease duration is ≤3 years, future follow-up duration is ≥4 years and informed consent is obtained. The expert committee has classified the included patients into: definite paediatric BD (PED-BD), probable PED-BD and no PED-BD. Statistical analysis is performed to compare the three groups of patients. Centres document their patients into a single database. Results. At January 2010, 110 patients (56 males/54 females) have been included. Mean age at first symptom: 8.1 years (median 8.2 years). At inclusion, 38% had only one symptom associated with ROA, 31% had two and 31% had three or more symptoms. A total of 106 first evaluations have been done. Seventeen patients underwent the first-year evaluation, and 36 had no new symptoms, 12 had one and 9 had two. Experts have examined 48 files and classified 30 as definite and 18 as probable. Twenty-six patients classified as definite fulfilled the International Study Group criteria. Seventeen patients classified as probable did not meet the international criteria. Conclusion. The expert committee has classified the majority of patients in the BD group although they presented with few symptoms independently of BD classification criteri