Gilda Sandri

Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: Results from the GISEA register

INTRODUCTION Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX). OBJECTIVES To evaluate the efficacy and safety of RTX-MTX combination therapy compared with RTX alone in the treatment of RA. METHODS We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed. RESULTS We identified 338 RA patients, 162 treated with RTX and 176 with RTX-MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX-MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX+MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX+MTX and RTX, respectively; while 12 patients (4.5% in RTX+MTX, and 2.5% in RTX group) suspended therapy for AE. CONCLUSIONS RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.

Immunodeficiency and autoimmune phenomena in female hyper-IgM syndrome.

Abstract:  We report an unusual case that highlights the clinical problems associated with autoimmune phenomena. A female (born 1972) was referred to our hospital with systemic lupus erythematosus (SLE) diagnosis. During the follow‐up (7 years), we observed the appearance and the disappearance of a lot of autoantibodies detected. The history of recurrent bacterial sinopulmonary infections since puberty and enlargement of lymphonodes, elevated IgM, very low IgA and normal IgG levels, and the variable autoantibody profile oriented toward a “defective Ig class switch recombination” disorder: the hyper‐IgM syndrome. Immunodeficiency and autoimmune phenomena may occur concomitantly in the same individual and sometimes the differential diagnosis is difficult.

Ultrasonography in the diagnosis and management of patients with inflammatory arthritides.

In primary care and internal medicine settings clinicians are often reluctant to take advantage of the resources that ultrasonography (US) offers as a diagnostic tool in the initial management of patients with inflammatory arthritis, despite the recognised importance of an accurate and timely diagnosis of rheumatoid arthritis (RA) and of early referral to ensure optimal patient management. Both grey-scale (GS) and power Doppler (PD) imaging have been extensively used in early detection of synovitis and bone erosions in patients with inflammatory arthritides. We reviewed the main data on the clinical use of US in the initial management of patients with inflammatory arthritis, focusing on RA diagnosis in patients with undifferentiated arthritis, prediction of disease severity, differential diagnoses and assessment of synovitis in children with juvenile idiopathic arthritis (JIA). The role of US in assessing treatment response and monitoring disease activity in clinical remission was also briefly evaluated. The reliability of US as a diagnostic tool in rheumatological diseases has greatly advanced in the last years and the use of this imaging technique, in association with conventional assessments such as physical examination and serological tests, should be considered more often also in primary care settings.

Large Vessel Vasculitis Occurring in Rheumatoid Arthritis Patient under Anti-TNF Therapy.

Vasculitis is a heterogeneous group of disorders characterized by the presence of necrotic inflammatory phenomena and destruction of blood vessels. Vasculitis is classified as primary (idiopathic) or secondary to infections, connective tissue diseases and drugs but can also be considered as a paraneoplastic phenomenon. Evidence shows that the increasing use of biological agents results in a growing number of reports of autoimmune diseases induced by these therapies. An inflammatory articular chronic disease such as rheumatoid arthritis may be complicated by extra-articular manifestations, such as cutaneous or systemic vasculitis. Herewith, we describe the case of a great vessels arteritis in a patient affected by rheumatoid arthritis in therapy with an anti-TNF agent (etanercept).

Epstein-Barr Virus Reactivation after Infliximab in Rheumatoid Arthritis: A Case Report

TNF-alpha blockers represent one of the most important therapeutic strategies for rheumatoid arthritis, but their use has raised the question about their safety profile, particularly in respect to viral infections/reactivations. We describe the case of a patient who developed a symptomatic EBV reactivation 11 days after the first infusion of infliximab.

Beyond Cat Scratch Disease: A Case Report of Bartonella Infection Mimicking Vasculitic Disorder

Cat scratch disease (CSD) is a bacterial disease caused by Bartonella henselae and it is mainly characterized by self-limiting lymphadenopathy in the draining site of a cat scratch or bite. We report a patient with history of fever, swelling lymph nodes, vasculitic-like skin lesions, and positivity of Bartonella serology initially considered as expression of a disimmune disease.

FRI0234 Complement depletion in rheumatoid arthritis patients treated with tocilizumab: a marker of clinical efficacy?

Objectives Tocilizumab (TCZ) is a humanized monoclonal antibody against the α-chain of the IL6 receptor. In clinical trials TCZ had been shown to lower complement levels in Rheumatoid Arthritis (RA) patients independently of disease activity. We therefore evaluated complement factors in our series of patients treated with anti IL6 to show whether there was any correlation. Methods 16 patients with active RA (14 F/2 M; mean age 56.3±11.2SD) were treated with TCZ (13 after anti-TNF failure and 3 naives). The patients were monitored for therapy response (DAS 28), HAQ, including clinical and laboratory parameters. All patients received DMARDs treatment and prednisolone ≤ 7.5 mg/day. Results Prior to the treatment, therapy complement levels were normal: C3 124.65±14.52 and C4 23.88±7.23 (normal values: C3 90-180 mg/dl, C4 10-40 mg/dl). Revaluation of these parameters revealed a decrease already after the first 3-month treatment. The complement depletion increased at the 6th month and persisted during the ongoing therapy. After the 12th month mean values were C3 89.35±10.21 and C4 11.64±6.39. In four patients the treatment was stopped for the clinical remission with normalization of C3/C4 factors in the follow-up. Concerning the RA disease activity, 14/16 patients showed a good EULAR response (initial DAS28: 5.79±0.86, ESR 41.94±18.81, CRP 3.62±3.14, HAQ 1.39±0.71; after 3 months DAS 28 2.23±0.52, ESR 6.13±3.10, CRP 0.27±0.24, HAQ 0.79±0.73). After 24 weeks, for 2/16 patients (1F/1M) the therapy was stopped for inefficacy; in both patients the levels of complement factors did not decrease during TCZ treatment. In all patients no signs for the development of autoimmunity or infection could be observed. Conclusions In the Tocilizumab OPTION study, mean levels of complement proteins C3 and C4 decreased but the data were not shown. It can be hypothesized that complement factors are consumed during the elimination process of immune complexes (IL6-anti-IL6Ab); moreover, in a case report of six RA patients the authors commented that this phenomenon requires further observation with respect to the clinical relevance. In an open label, dose-escalating, Phase I study Tocilizumab in Systemic Lupus Erythematosus complement C3 and C4 showed clear dose-related decreases. The Authors of such trial provided the first evidence that the TCZ-associated hypocomplementemia represents decreased production rather than increased activation. Also Olokizumab, a novel IL6 inhibitor in trials showed in RA patients the same dose-related reductions in complement C3 and C4. Reduction in complement levels is therefore believed to be consecutive to the inhibition by TCZ of IL6 stimulation of hepatocyte acute phase protein synthesis and of significant C3 upregulation. In our patients there is a good correlation between C3 and C4 decrease and clinical response, while we have not observed any decrease in patients unresponsive to TCZ. The levels of C3 and C4 are more related to the efficacy than PCR or ESR values, which in 1 patient decreased in absence of clear clinical improvement. The number of patients is too small to reach a conclusion but we hypothesize that the dosage of the C3 and C4 can be a rapid and sensitive marker of the response to anti-IL6 treatment. Therefore, a close follow-up of these parameters at 2-3 months from the start of the therapy can guide the therapeutic strategy. Disclosure of Interest: None Declared