Gianfranco Vitiello

A Snapshot on the On-Label and Off-Label Use of the Interleukin-1 Inhibitors in Italy among Rheumatologists and Pediatric Rheumatologists: A Nationwide Multi-Center Retrospective Observational Study

Background: Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis. Objectives: To perform a nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults. Methods: We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016. Results: Five hundred and twenty-six treatment courses given to 475 patients (195 males, 280 females; 111 children and 364 adults) were evaluated. ANA was administered in 421 (80.04%) courses, CAN in 105 (19.96%). Sixty-two (32.1%) patients had been treated with both agents. IL-1 inhibitors were employed in 38 different indications (37 with ANA, 16 with CAN). Off-label use was more frequent for ANA than CAN (p < 0.0001). ANA was employed as first-line biologic approach in 323 (76.7%) cases, while CAN in 37 cases (35.2%). IL-1 inhibitors were associated with corticosteroids in 285 (54.18%) courses and disease modifying anti-rheumatic drugs (DMARDs) in 156 (29.65%). ANA dosage ranged from 30 to 200 mg/day (or 1.0–2.0 mg/kg/day) among adults and 2–4 mg/kg/day among children; regarding CAN, the most frequently used posologies were 150mg every 8 weeks, 150mg every 4 weeks and 150mg every 6 weeks. The frequency of failure was higher among patients treated with ANA at a dosage of 100 mg/day than those treated with 2 mg/kg/day (p = 0.03). Seventy-six patients (14.4%) reported an adverse event (AE) and 10 (1.9%) a severe AE. AEs occurred more frequently after the age of 65 compared to both children and patients aged between 16 and 65 (p = 0.003 and p = 0.03, respectively). Conclusions: IL-1 inhibitors are mostly used off-label, especially ANA, during adulthood. The high frequency of good clinical responses suggests that IL-1 inhibitors are used with awareness of pathogenetic mechanisms; adult healthcare physicians generally employ standard dosages, while pediatricians are more prone in using a weight-based posology. Dose adjustments and switching between different agents showed to be effective treatment strategies. Our data confirm the good safety profile of IL-1 inhibitors.

Response to interleukin-1 inhibitors in 140 Italian patients with adult-onset still's disease: A multicentre retrospective observational study

Background: Interleukin (IL)-1 plays a crucial role in the pathogenesis of Adult onset Still’s disease (AOSD). Objectives: To evaluate the efficacy and safety of anakinra (ANA) and canakinumab (CAN) in a large group of AOSD patients. Methods: Data on clinical, serological features, and concomitant treatments were retrospectively collected at baseline and after 3, 6, and 12 months from AOSD patients (Yamaguchi criteria) referred by 18 Italian centers. Pouchot’s score was used to evaluate disease severity. Results: One hundred forty patients were treated with ANA; 4 were subsequently switched to CAN after ANA failure. The systemic pattern of AOSD was identified in 104 (74.2%) of the ANA-treated and in 3 (75%) of the CAN-treated groups; the chronic-articular type of AOSD was identified in 48 (25.8%) of the ANA-treated and in 1 (25%) of the CAN-treated groups. Methotrexate (MTX) was the most frequent disease modifying anti-rheumatic drug (DMARD) used before beginning ANA or CAN [91/140 (75.8%), 2/4 (50%), respectively]. As a second-line biologic DMARD therapy in 29/140 (20.7%) of the patients, ANA was found effective in improving all clinical and serological manifestations (p < 0.0001), and Pouchot’s score was found to be significantly reduced at all time points (p < 0.0001). No differences in treatment response were identified in the ANA-group when the patients were stratified according to age, sex, disease pattern or mono/combination therapy profile. ANA primary and secondary inefficacy at the 12-month time point was 15/140 (10.7%) and 11/140 (7.8%), respectively. Adverse events (AEs) [mainly represented by in situ (28/47, 59.5%) or diffuse (12/47, 25.5%) skin reactions and infections (7/47, 14.8%)] were the main causes for discontinuation. Pouchot’s score and clinical and serological features were significantly ameliorated at all time points (p < 0.0001) in the CAN-group, and no AEs were registered during CAN therapy. Treatment was suspended for loss of efficacy only in one case (1/4, 25%). Conclusion: This is the largest retrospective observational study evaluating the efficacy and safety of IL-1 inhibitors in AOSD patients. A good response was noted at 3 months after therapy onset in both the ANA- and CAN-groups. Skin reaction may nevertheless represent a non-negligible AE during ANA treatment.

Sustained tocilizumab-induced hypofibrinogenemia and thrombocytopenia. Comment on: “Tocilizumab-induced hypofibrinogenemia: A report of 7 cases” by Martis et al., Joint Bone Spine 2016, doi: 10.1016/j.jbspin.2016.04.008

Joint Bone Spine - In Press.Proof corrected by the author Available online since jeudi 11 mai 2017

Bench to bedside review of myositis autoantibodies

Idiopathic inflammatory myopathies represent a heterogeneous group of autoimmune diseases with systemic involvement. Even though numerous specific autoantibodies have been recognized, they have not been included, with the only exception of anti-Jo-1, into the 2017 Classification Criteria, thus perpetuating a clinical-serologic gap. The lack of homogeneous grouping based on the antibody profile deeply impacts the diagnostic approach, therapeutic choices and prognostic stratification of these patients. This review is intended to highlight the comprehensive scenario regarding myositis-related autoantibodies, from the molecular characterization and biological significance to target antigens, from the detection tools, with a special focus on immunofluorescence patterns on HEp-2 cells, to their relative prevalence and ethnic diversity, from the clinical presentation to prognosis. If, on the one hand, a notable body of literature is present, on the other data are fragmented, retrospectively based and collected from small case series, so that they do not sufficiently support the decision-making process (i.e. therapeutic approach) into the clinics.

Large-vessel Involvement and Varicella Zoster Virus Vasculopathy in Giant Cell Arteritis–related Stroke: Something to Keep an Eye On

To the Editor: We have read with great interest the original article written by de Boysson, et al 1. This multicenter retrospective study highlighted the vasculitic-related risk of stroke in patients with newly diagnosed giant cell arteritis (GCA) and how it was related to ophthalmic ischemic impairment and to lower systemic inflammatory markers (i.e., lower acute-phase proteins level and lower risk of anemia) in comparison with GCA patients without stroke. Concerning this, in our cohort of 82 patients with a GCA diagnosis according to the 1990 American College of Rheumatology criteria, 6 (mean age at diagnosis 73.5 ± 8.89 yrs; … Address correspondence to Dr. G. Vitiello, Experimental and Clinical Medicine Department, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, 50123 Florence, Italy. E-mail: vit.gianfranco{at}gmail.com

First report of anti-TIF1γ dermatomyositis in a patient with myelodysplastic syndrome

Inflammatory myopathies as para-neoplastic phenomena were first described by Sterz in 1916. Recently, myositis specific autoantibodies were described in cancer-associated myositis. Anti-transcription intermediary factor 1 gamma (anti-TIF1γ) antibodies have been found in both young adults affected by juvenile dermatomyositis and in elderly patients with cancer-associated myositis. In this regard, we report herein the first case of anti-TIF1γ dermatomyositis secondary to a myelodysplastic syndrome.

Tocilizumab in Giant Cell Arteritis: A Real-Life Retrospective Study

This study aims to evaluate (1) the efficacy and safety of tocilizumab (TCZ) as a steroid-sparing agent in patients with giant cell arteritis (GCA) and (2) the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the follow-up and to detect disease activity. We retrospectively evaluated 12 patients with GCA treated with TCZ (8 mg/kg/mo). Pre- and posttherapy data about clinical signs and symptoms, laboratory results, FDG-PET imaging study, and the mean glucocorticoid (GC) dose were used to assess disease activity. Tocilizumab achieved complete disease remission in all patients. Mean FDG-PET-detected standard uptake value decreased from 2.05 ± 0.64 to 1.78 ± 0.45 (P = .005). In 2 patients in whom temporal arteries color Doppler sonography examination was consistent with temporal arteritis, the hypoechoic halo disappeared after TCZ treatment. Mean GC dose was tapered from 26.6 ± 13.4 mg/d to 3.3 ± 3.1 mg/d (P < .0001). One-half of the patients discontinued GC therapy. Three patients experienced severe adverse reactions and had to stop TCZ therapy. In accordance with previous reports, TCZ is an effective steroid-sparing agent for GCA, although careful monitoring of adverse drug reactions is needed. 18F-fluorodeoxyglucose positron emission tomography could be used to monitor disease activity in TCZ-treated patients, but prospective studies are needed to confirm these data.