Marta Fabbroni

Drug Retention Rates and Treatment Discontinuation among Anti-TNF-α Agents in Psoriatic Arthritis and Ankylosing Spondylitis in Clinical Practice

Objective. The study aim was to determine treatment persistence rates and to identify causes of discontinuation in psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients in clinical practice. Methods. Patients treated with adalimumab (ADA), etanercept (ETA), or infliximab (INF) were retrospectively included. Treatment persistence rates were analyzed by means of a stepwise logistic regression. Differences between therapy duration were assessed by means of an analysis of variance model (ANOVA), while a chi-square test was used to evaluate relationships between therapies and causes of treatment discontinuation and the administration of concomitant disease-modifying antirheumatic drugs (DMARDs) among therapies and types of disease considering completed courses of therapy versus courses that were discontinued. Results. 268 patients received a total of 353 anti-TNF treatment courses (97 ADA, 180 ETA, and 76 INF). Comparison among therapies showed significant difference regarding the treatment persistence rates due to the contrast between ETA and INF (P = 0.0062). We observed that 84.7% of patients were still responding after 6 months of follow-up. Comparison among diseases showed that there were significant differences between PsA and AS (P = 0.0073) and PsA and PsA with predominant axial involvement (P = 0.0467) in terms of duration of the therapy, while there were no significant differences with regard to the persistence rate. Conclusions. In this cohort, anti-TNF-α therapy was associated with high drug persistence rates. As in rheumatoid arthritis, switching to another anti-TNF-α agent can be an effective option when, during the treatment of AS or PsA, therapy is suspended because of inefficacy or an adverse event. Combination therapy with DMARDs was associated with a better persistence rate.

Cartilage oligomeric matrix protein level in rheumatic diseases: potential use as a marker for measuring articular cartilage damage and/or the therapeutic efficacy of treatments.

Abstract:  Cartilage oligomeric matrix protein (COMP) is a tissue‐specific noncollagenous protein that was first detected in the serum and the synovial fluid of patients suffering from rheumatic disorders, such as rheumatoid arthritis, reactive arthritis, juvenile chronic arthritis, and osteoarthritis. In this review, the authors consider serum COMP levels in different diseases and discuss their study of patients with rheumatoid arthritis treated with anti‐TNF‐α, to evaluate whether COMP is able to predict a rapid and sustained clinical response to these drugs. They observe that patients with high COMP levels have a lower ACR 70 response independently of the state of systemic inflammation, and conclude that COMP seems to have a pathogenetic role that is independent of the mechanisms regulating inflammatory processes.

Switch from infliximab to infliximab biosimilar: efficacy and safety in a cohort of patients with different rheumatic diseases

Dear Editor in Chief We read with great interest the manuscript by Nikiphorou et al. describing the effectiveness of infliximab-biosimilar CTP13 (INB) used as a switch from Remicade® (Janssen Biotech, Inc., Horsham, PA, USA) (infliximab (INX)) in patients with different established rheumatic diseases [1]. Thirty-nine patients on INX were switched to biosimilar after a mean time (SD) of 4.1 (2.3) years. The authors reported that INB clinical effectiveness, during the first year of switching, was comparable to INX in both the patient-reported outcomes and disease-activity measures, with no immediate safety signals. Eleven patients (28.2%) discontinued INB due to INX antibodies detected prior to INB infusion (3/11), latent tuberculosis (1/11), new-onset neurofibromatosis (1/11), and subjective reasons with no objective deterioration of disease (6/ 11). The authors suggested that subjective reasons, such as negative expectations, played a key role among INB discontinuations. In this regard, we report herein our experience in a cohort of 23 patients followed in our unit for different rheumatic diseases and switched, for local regulatory issues, to INB (Inflectra®) after amean time (SD) of 71.65 (44.40) months on INX (Remicade). More in detail, 11 out of 23 had psoriatic arthritis (7 with peripheral and 4 with axial involvement), 8/23 ankylosing spondylitis, 2/23 rheumatoid arthritis, 2/23 Crohn’s disease and associated axial spondyloarthritis, and 1/23 Behçet’s disease and associated axial spondyloarthritis. At the time of the switch, all of the patients were in complete disease remission on INX at a dose of 5 mg/kg every 8 weeks. After a mean time of 1.71 months (range 1–2) from the start of INB a disease relapse occurred in 7 out of 23 patients (30.43%). Their mean (SD) duration of previous INX treatment was 62.28 (49.95) months. Table 1 summarizes the clinical, demographic, and therapeutic data of the 7 subjects unresponsive to INB. INB was then suspended and IFX was readministered in all 7 patients at a dose of 5 mg/kg every 8 weeks, in association with a tapering dose of oral corticosteroids. In 5/7, the readministration of INX promptly led to a remarkable clinical improvement (4/5), or at least a partial one (1/5), with a significant decrement of the disease activity indexes. No amelioration was observed in 2/7 subjects. Among the 16 patients that were still on treatment with INB, 7 of them were under close observation and monitoring for uveitis relapse (1/7), recurrence of psoriatic lesions (1/7), arthralgia (4/7), and referredworsening of global quality of life (1/7). No changes in the response to treatment were observed in 9 out of 23 subjects (39.13%). INB was well tolerated and no adverse events were noted. In PLANETAS and PLANETRA studies, INB demonstrated equivalent efficacy to INX at 30-week follow-up, with a comparable pharmacokinetic profile and immunogenicity both in patients affected by ankylosing spondylitis (AS) and rheumatoid arthritis (RA) [2,3]. INB efficacy and safety have been confirmed also in the extension of the PLANETAS study in AS at 54-week follow-up [4]. Nevertheless, data on the effectiveness of the switch from INX to INB in patients in a stable disease remissionwhile on IFX are scarce, and future studies are needed. For the above reason, real-life data should be welcome, even though from uncontrolled series, until further trials are performed. In our cohort of patients, 30% of subjects switched from IFX to INB while in disease remission showed a rapid worsening of disease activity indexes. Moreover, 30% of patients still on treatment with INB were under evaluation for the potential reduction of the interval between INB administrations either the potential increase of INB dosage or a further switch from INB to IFX, due to a suspected lack of efficacy. Overall, it is unlikely that in our cohort of patients, only subjective reasons have played a role in the poor outcome observed in most subjects. Indeed, we did not observe any change in the response to treatment in only 40% of cases. Limitations of our study were the small number of patients, the absence of a control group, and the short-

Effectiveness of Adalimumab in Non-radiographic Axial Spondyloarthritis: Evaluation of Clinical and Magnetic Resonance Imaging Outcomes in a Monocentric Cohort.

Abstract The primary aim of the study was to evaluate the long-term effectiveness of adalimumab (ADA) in a cohort of non-radiographic axial spondyloarthritis (nr-axSpA), and the secondary aims were to identify predictive factors of response and evaluate radiological progression. We evaluated 37 patients (male/female: 12/25; mean age 49 ± 14; mean disease duration: 6.3 ± 5.8) with active nr-axSpA (Assessment of SpondyloArthritis International Society criteria), despite the treatment with ≥1 nonsteroidal anti-inflammatory drug for at least 3 months, initiating the treatment with ADA 40 mg every other week. Patients were treated for 24 months, and evaluated at baseline, 6, 12, and 24 months. Outcome measures included Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Functional Index. Radiograph of the spine and sacroiliac joints and magnetic resonance of the sacroiliac joints were performed at baseline and according to the standard of assessment for the disease. The proportion of patients that achieved a BASDAI50 response at 6, 12 and 24 months was 51.3%, 70.3%, and 76.8%, respectively. Treatment was well tolerated with no unexpected adverse events and/or serious adverse events. All patients remained on treatment for 2 years, with a good compliance. We did not identify any predictive factor of response to therapy. Moreover, modified Stoke Ankylosing Spondylitis Spine Score and Spondyloarthritis Research Consortium of Canada scores showed a trend of improvement during the study period. ADA was effective on clinical and radiological outcomes at 2-year follow-up; thus, early treatment with ADA may prevent radiographic damage and be associated with low disease activity or remission. Moreover, data from this cohort study have confirmed safety and tolerability profile of ADA in nr-axSpA in the long term.

Intravenous Immunoglobulins as a new opportunity to treat discoid lupus erythematosus: A case report and review of the literature

Discoid lupus erythematosus (DLE) is a chronic dermatological disease that can lead to scarring, alopecia and dyspigmentation, if not properly treated. Actually, no drugs are specifically approved for the treatment of CLE, although the first-line therapy usually consists of photoprotection associated to topical or oral steroids, topical calcineurin inhibitors and hydroxychloroquine (HCQ). In cases of DLE refractory to these medications, many other agents have been employed, such as dapsone, methotrexate, azathioprine, cyclophosphamide, biologic drugs and Intravenous Immunoglobulin (IVIG). We described the case of a DLE patient resistant to combination therapy with steroid and HCQ who was successfully treated with cyclical IVIG therapy. The treatment with IVIG resulted rapidly effective with persistent efficacy and low rates of relapses, although more cycles of IVIG are needed to achieve a stable clinical remission. We also discussed the beneficial and promising effects of IVIG in patients with Cutaneous Lupus reporting the previously published data.

SAT0384 Long-Term Safety of Anti-Tnf Agents in Patients with Spondyloarthritis and Potential Occult HBV: An Observational Multicenter Study on 131 Patients

Background drugs targeting tumor necrosis factor-α (TNF) biological activity deal with an increased risk of infections. Few papers address whether TNF blockers in rheumatic patients with potential HBV occult infection are safe (1–9). Objectives to evaluate the safety of anti-TNF agents in cases of spondyloarthritis with resolved hepatitis B (HBsAg negative, HBcAb±anti-HBs positive) through a close monitoring of a possible HBV reactivation and/or rise in the aminotransferase levels. Methods the medical records for 992 outpatients with rheumatic inflammatory diseases attending two Italian Rheumatology Units between 2007–2015 were retrospectively reviewed for diagnosis of spondyloarthritis, current treatment with anti-TNF agents and seropositivity for past HBV infection. 131 patients (70 men, 61 women; mean age:60,63±9,59 years) were included in the study: 55 with ankylosing spondylitis, 65 psoriatic arthritis, 9 inflammatory bowel disease-associated arthritis, 2 non-radiographic axial spondyloarthritis. Mean disease duration was 98,64±42,60 months. 64 patients were currently in treatment with Etanercept (29 in monotherapy, 31 with MTX, 3 with SSZ, 1 with CsA); 32 with Infliximab (18 as monotherapy, 10 with MTX, 3 with SSZ, 1 with CsA); 31 with Adalimumab (16 in monotherapy, 12 with MTX, 2 with LEF, 1 with CsA); 4 with Golimumab (3 with MTX, 1 as monotherapy). 101 patients received only 1 TNF inhibitor (54 Etanercept, 27 Infliximab, 20 Adalimumab); 23 patients switched to a second and 7 patients switched to a third anti-TNF agent. 51 patients had concomitant prednisone <12,5 mg/die. All 131 patients were anti-HBc+, of which 109 were anti-HBc and anti-HBs+. No patient was positive for HBV-DNA at baseline, none received antiviral therapy prior to or during anti-TNF treatment. Results at the end of the follow-up (mean of 75,50±33,37 months of anti-TNF therapy), no case of viral reactivation was observed in anti-HBc+ patients, no matter anti-HBs positivity. HBV-DNA remained undetectable, HBsAg negative, aminotransferases normal, nor it was necessary to stop biologic therapy because of viral infection. Conclusions our retrospective analysis supports the safety of TNF inhibitors for spondyloarthritis patients with a serological pattern of previous HBV infection during a follow-up >6 years. Pre-emptive antiviral prophylaxis is not necessary routinely, but strict monitoring for AST/ALT increase, as well as for changes in HBV serology and HBV-DNA, is necessary and seems a cost-effective approach to identify early viral reactivation, whose occurrence is low, but not negligible, and consequently start antiviral therapy. References Kim et al. J Rheumatol 2010;2)Vassilopoulos et al. ARD 2010;3)Caporali et al. Arthritis Care Res 2010;4)Giannitti et al. J Rheumatol 2011;5)Lan et al. ARD 2011;6)Lee et al. Clin Exp Rheumatol 2013;7)Cantini et al. Int J Rheumatol 2014;8)Biondo et al. Eur J Intern Med 2014;9)Barone et al. Hepatology 2015 Disclosure of Interest None declared