Christos Koutsianas

Anakinra for the management of resistant idiopathic recurrent pericarditis. Initial experience in 10 adult cases

Recurrent idiopathic pericarditis is a common, problematic complication of acute pericarditis, occurring in approximately 30% of cases.1 Despite appropriate management with non-steroidal anti-inflammatory drugs (NSAIDs), colchicine and corticosteroids (CS), a number of patients are either resistant to treatment requiring long-term therapy with high doses of CS or intolerant to therapy.2–4 This disease is currently viewed as an autoinflammatory disease based on its clinical and laboratory features (recurrent episodes of sterile serosal inflammation in the absence of specific autoreactive antibodies or T cells),5–7 and the preliminary results showing favourable response to intereleukin-1 (IL-1) inhibition.8–10 Anakinra, a known IL-1 receptor antagonist, has been successfully used in small series of paediatric patients8 ,9 while we have recently first reported its efficacy and safety in three adult patients.10 In this report, we extend our follow-up on these three patients, and present data on seven more adult patients treated with anakinra. …

Frequent conversion of tuberculosis screening tests during anti-tumour necrosis factor therapy in patients with rheumatic diseases

Objectives To determine the rate of tuberculosis (TB) screening test conversion during anti-tumour necrosis factor (TNF) therapy in rheumatic patients with negative baseline screening. Methods This was a prospective study of rheumatic patients with negative baseline TB screening (tuberculin skin test (TST): <5 mm, and negative T-SPOT.TB, QuantiFERON-TB Gold In Tube (QFT-GIT) and chest X-ray) treated with anti-TNF agents. All patients underwent re-screening for TB with all assays 1 year later. Factors associated with TB test conversion were analysed and compared between ‘converters’ and ‘non-converters’. Results Seventy patients (mean age 50.6±15.5 years) with rheumatic disease (33 with rheumatoid arthritis, 33 with spondyloarthropathies and 4 with other conditions) were enrolled. Patients were treated with different anti-TNFs (27 with adalimumab, 14 etanercept, 16 infliximab, 8 golimumab, 5 certolizumab pegol) for 1 year. Twenty patients (29%) displayed conversion of at least one screening assay 12 months after anti-TNF therapy: conversion of TST occurred in 9 (13%), T-SPOT.TB in 7 (10%) and QFT-GIT in 5 (7%). Only one patient had concomitant conversion of more than one screening test. Univariate and multivariate analysis revealed that only infliximab was associated with a decreased rate of TB screening assay conversion (OR 0.048, 95% CI 0.004 to 0.606, p=0.017). No patient (40% received isoniazid therapy) developed active TB during follow-up (27±12 months). Conclusions Approximately one third of patients with negative baseline TB screening develop conversion of at least one screening test during anti-TNF treatment. These findings should be considered when designing re-screening strategies and contemplating latent TB therapy.

Hepatitis B Reactivation in Rheumatic Diseases : Screening and Prevention

Hepatitis B virus (HBV) reactivation (HBVr) has been an increasingly recognized and appreciated risk of immunosuppressive therapies in rheumatic patients. Despite its potential for significant morbidity and mortality, HBVr is a fully preventable complication with appropriate pretreatment screening and close monitoring of susceptible patients. Better knowledge of the risk for HBVr with the different antirheumatic agents and the establishment of the new-generation oral antivirals in clinical practice has greatly improved the design of screening and therapeutic algorithms. In this review, all available data regarding HBVr in rheumatic patients are critically presented and a screening and therapeutic algorithm is proposed.

Prevention of HBV reactivation in patients treated with biologic agents

ABSTRACT Owing to the sensitive equilibrium between the hepatitis B virus (HBV) and the host’s immune system in infected and exposed individuals, the immunosuppression caused by biologic treatment has been strongly linked to HBV reactivation (HBVr). HBVr in the setting of biologic therapy is a cause of considerable morbidity, hospitalization, interruption of treatment and mortality. However, recent literature has established that this is a largely preventable problem. Thus, it is essential for clinicians using biologic agents to be aware of HBVr potential and screen all susceptible patients. The risk for HBVr may vary depending on the host’s HBV infection status and the potency of immunosuppression. The appropriate pre-emptive antiviral prophylaxis or monitoring for individuals at risk is emphasized in the latest evidence-based guidelines, but a number of unanswered questions remain.

Increased Frequency of Peripheral B and T Cells Expressing Granulocyte Monocyte Colony-Stimulating Factor in Rheumatoid Arthritis Patients

Objectives Granulocyte monocyte colony-stimulating factor (GM-CSF) is currently considered a crucial inflammatory mediator and a novel therapeutic target in rheumatoid arthritis (RA), despite the fact that its precise cellular sources remain uncertain. We studied the expression of GM-CSF in peripheral lymphocytes from RA patients and its change with antirheumatic therapies. Methods Intracellular GM-CSF expression was assessed by flow cytometry in stimulated peripheral B (CD19+) and T (CD3+) cells from RA patients (n = 40), disease (n = 31 including osteoarthritis n = 15, psoriatic arthritis n = 10, and systemic rheumatic diseases n = 6) and healthy (n = 16) controls. The phenotype of GM-CSF+ B cells was assessed as well as longitudinal changes in GM-CSF+ lymphocytes during methotrexate (MTX, n = 10) or anti-tumor necrosis factor (anti-TNF, n = 10) therapy. Results Among untreated RA patients with active disease (Disease Activity Score 28-C-reactive protein = 5.6 ± 0.89) an expanded population of peripheral GM-CSF+ B (4.1 ± 2.2%) and T (3.4 ± 1.6%) cells was detected compared with both disease (1.7 ± 0.9%, p < 0.0001 and 1.7 ± 1.3%, p < 0.0001, respectively) and healthy (0.3 ± 0.2%, p < 0.0001 and 0.6 ± 0.6%, p < 0.0001) controls. RA GM-CSF+ B cells displayed more commonly a plasmablast or transitional phenotype (37.12 ± 18.34% vs. 14.26 ± 9.46%, p = 0.001 and 30.49 ± 15.04% vs. 2.45 ± 1.84%, p < 0.0001, respectively) and less a memory phenotype (21.46 ± 20.71% vs. 66.99 ± 16.63%, p < 0.0001) compared to GM-CSF− cells. GM-CSF expression in RA patients did not correlate to disease duration, activity or serological status. Anti-TNF treatment led to a statistically significant decrease in GM-CSF+ B and T cells while MTX had no significant effect. Discussion This is the first study showing an expanded population of GM-CSF+ B and T lymphocytes in patients with active RA which declined after anti-TNF therapy.

FRI0160 Comparative Drug Survival of Different Non-Anti-TNF IV Biologics After Anti-TNF Failure in Rheumatoid Arthritis Patients

Background There are limited data to guide the selection of the first non-anti-TNF biologic DMARD (bDMARDs) after anti-TNF failure in rheumatoid arthritis (RA) patients. Objectives To evaluate the drug survival of non-anti-TNF IV bDMARDs in RA patients with inadequate response to ≥1 TNF inhibitors (TNF-IR) in daily clinical practice. Methods All TNF-IR patients treated with different non-anti-TNF bDMARDS in our center between 01/01/2007 to 31/12/2014 were included in the study. Analyses were stratified by the first biologic agent used after TNF failure (Tocilizumab-TCZ, Rituximab-RTX, Abatacept-ABA) and then by RF status and conventional synthetic DMARD (csDMARD) administration. Kaplan-Meier survival analysis and log-rank test of equality pairwise over strata were performed. Results 94 TNF-IR consecutive RA patients treated with TCZ (n=24), RTX (n=49) or ABA (n=21) were included and followed for 24.2±18.8 months. 84/94 (89.4%) were women with a mean age of 64.5±15 years, rheumatoid factor (RF) positive were 49/94 (52%) patients. The baseline characteristics did not differ between the 3 groups, except from RF positivity which was more common in the RTX group compared to the TCZ group (p=0.01). The drug survival rates for TCZ, RTX and ABA were 79%, 83% and 76% at 12 months and 60%, 68%, 44% at 24 months, respectively (p=NS). Similarly, the mean time for drug discontinuation was 29.7, 41.7 and 27.1 months respectively and did not differ between groups (p=NS). Among RF+ patients, RTX (p=0.007) and TCZ (p=0.05) demonstrated better survival compared to ABA while there was no difference in drug survival among RF negative patients. There was a tendency for better drug survival among RA patients treated with RTX in combination with csDMARDs compared to combination ABA therapy (p=0.06) but this did not reach statistical significance. Conclusions In this observational retrospective study, overall there was no significant difference in drug survival, between non-anti-TNF bDMARDs after anti-TNF failure, with the exception of RF+ patients where RTX and TCZ demonstrated better survival compared to ABA. Acknowledgements This work was supported in part by research grants from the Special Account for Research Grants (S.A.R.G.), National and Kapodistrian University of Athens, Athens, Greece. Disclosure of Interest None declared

AB0654 Efficacy and Safety of Rituximab in Patients with Anca Associated Vasculitis in Real Life

Background Rituximab (RTX) is a novel, recently approved therapeutic agent for the treatment of active ANCA-associated vasculitis (AAV, Granulomatosis with polyangiitis-GPA, Microscopic polyangiitis-MPA) with limited data available from daily clinical practice. Objectives To study the efficacy and safety of RTX in patients with AAV in real life settings. Methods Retrospective study of all patients with active AAV treated with RTX in our tertiary center between 2010 and 2015. Results 16 patients with active AAV were included (GPA n=12, MPA n=4); 50% females with a mean age of 61.8±13.9 years and median disease duration of 33.5 months. The majority of patients had generalized disease (88%) and the most commonly involved organs were lungs (75%), kidney (63%), joints (50%) and ENT (31%). The patients were followed for a mean period of 21.5±16.1 months. Eleven (68%) patients were treated with RTX due to resistant or relapsing disease and 5 (32%) received RTX as initial treatment. Seven patients received 1 cycle, one patient 2 cycles and 8 patients received ≥3 cycles of RTX (1 gm x 2, 15 days apart). Among patients who received ≥1 cycle of RTX (n=9), 6 received RTX on a regular basis (every 6 months) and 3 at relapse. During treatment, a statistically significant improvement in disease activity was observed (BVAS/WG before RTX was 4.8 and decreased to 0.9 and 0.8 at 6 and 12 months, p=0.001 and 0.003 respectively). At 6 months, 87% of patients (13/15) responded to therapy (6 showed complete and 7 partial response). Additionally, one patient who had not responded at 6 months demonstrated complete response at 9 months. Among the 13 responders, 6 (46%) relapsed during follow up. The majority of relapses were minor (5/6, 83%) and occurred mainly in patients not receiving RTX in a regular basis (4/6, 67%). One patient with GPA and fulminant pulmonary-renal syndrome died from septic shock one month after RTX administration (6%). No other serious infections or allergic reactions were noticed during the follow up period. Conclusions These real life data confirm the excellent efficacy and safety of RTX in patients with active newly diagnosed or relapsing AAV. Acknowledgements This work was supported in part by research grants from the Special Account for Research Grants (S.A.R.G.), National and Kapodistrian University of Athens, Athens, Greece. Disclosure of Interest None declared