Subcutaneous infliximab CT-P13 without intravenous induction in psoriatic arthritis: A case report and pharmacokinetic considerations.

INTRODUCTION: The biosimilar CT-P13, the first and only subcutaneous (SC) infliximab formulation, is recommended for patients with psoriatic arthritis (PsA) and can be administered as a maintenance treatment, to be started 4 weeks after the induction treatment with 2 intravenous (IV) infliximab infusions. OBJECTIVE: To evaluate treatment with SC infliximab without prior IV infusion induction to meet patient needs. MATERIALS AND METHODS: After approval by the ethics review board and based on the schedule approved for rheumatoid arthritis, SC induction was performed with infliximab CT-P13 120 mg weekly for 4 weeks, followed by an injection of 120 mg every 2 weeks. RESULTS: After 4 months of therapy, joint symptoms were resolved, inflammation parameters were normalized (erythrocyte sedimentation rate) reduced from 42 to 16 mm/h, and C-reactive protein from 1.74 to 0.43 mg/dL), and clinical assessment parameters were improved. After 9 months of therapy, the clinical data remained stable, with no adverse events or local side effects. CONCLUSION: SC infliximab was successfully used without previous IV infusion induction. Although, to date, the induction of PsA treatment via the SC route is not foreseen, the known pharmacokinetic properties and the outcome improvements observed in our patient show that subcutaneous treatment induction, as is already done in the treatment of rheumatoid arthritis, is also possible.

Long-Term Retention Rate of Tofacitinib in Rheumatoid Arthritis: An Italian Multicenter Retrospective Cohort Study.

Background: Tofacitinib (TOFA) was the first Janus kinase inhibitor (JAKi) to be approved for the treatment of rheumatoid arthritis (RA). However, data on the retention rate of TOFA therapy are still far from definitive. Objective: The goal of this study is to add new real-world data on the TOFA retention rate in a cohort of RA patients followed for a long period of time. Methods: A multicenter retrospective study of RA subjects treated with TOFA as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) was conducted in 23 Italian tertiary rheumatology centers. The study considered a treatment period of up to 48 months for all included patients. The TOFA retention rate was assessed with the Kaplan-Meier method. Hazard ratios (HRs) for TOFA discontinuation were obtained using Cox regression analysis. Results: We enrolled a total of 213 patients. Data analysis revealed that the TOFA retention rate was 86.5% (95% CI: 81.8-91.5%) at month 12, 78.8% (95% CI: 78.8-85.2%) at month 24, 63.8% (95% CI: 55.1-73.8%) at month 36, and 59.9% (95% CI: 55.1-73.8%) at month 48 after starting treatment. None of the factors analyzed, including the number of previous treatments received, disease activity or duration, presence of rheumatoid factor and/or anti-citrullinated protein antibody, and presence of comorbidities, were predictive of the TOFA retention rate. Safety data were comparable to those reported in the registration studies. Conclusions: TOFA demonstrated a long retention rate in RA in a real-world setting. This result, together with the safety data obtained, underscores that TOFA is a viable alternative for patients who have failed treatment with csDMARD and/or biologic DMARDs (bDMARDs). Further large, long-term observational studies are urgently needed to confirm these results.

Baseline characteristics of systemic lupus erythematosus patients included in the Lupus Italian Registry of the Italian Society for Rheumatology.

OBJECTIVE: To report baseline data of SLE patients enrolled in the Lupus Italian Registry (LIRE). METHODS: Patients affected by SLE aged ≥ 16 years were consecutively recruited in a multicenter prospective study comparing two cohorts: patients starting biologic immunosuppressants (BC) and patients starting non-biologic immunosuppresants (NBC). RESULTS: 308 patients were enrolled, 179 in NBC and 129 in BC. Mean age at disease onset and at diagnosis was significantly higher in NBC (p = 0.023, p = 0.045, respectively). Disease duration was longer in BC (p = 0.022). Patients in BC presented arthritis more frequently (p = 0.024), those in NBC nephropathy (p = 0.03). Quality of life was worse in BC (p = 0.031). Anti-dsDNA, low C3, were significantly more frequent in BC (p < 0.001, p = 0.009, respectively). Mycophenolate, methotrexate and azathioprine were the drugs more frequently prescribed in NBC, Belimumab and Rituximab in BC. CONCLUSION: The predominant organ involvement was different in the two cohorts: kidney involvement predominated in NBC, joint involvement in BC. Despite the younger age at disease onset, patients of the BC had a longer disease duration and more frequently had taken a cumulative prednisone dosage greater than 10 g. Even the pattern of clinical manifestations inducing to prescribe biological rather than conventional immunosuppressants was quite different.Keywords: Autoantibody(ies), autoimmune disease, belimumab, cohort studies, glucocorticoids, immunosuppressants, rituximab, systemic lupus erythematosus.

Prevalence of hepatitis B virus infection and risk of reactivation in rheumatic population undergoing biological therapy.

OBJECTIVES: Hepatitis B (HBV) is a common comorbidity among rheumatic patients. The prevalence of HBV infection and the rate of reactivation remain unclear. The literature data suggested a higher risk in chronic than in past infection. Currently, the literature data are mostly focused on anti-TNF and rituximab. This retrospective observational study aimed to analyse the prevalence of HBV infection and the risk of viral reactivation in a population of rheumatic patients undergoing anti-TNF and non-anti-TNF agents. METHODS: We analysed 1216 rheumatic patients, treated with both csDMARDs and bDMARDs between 2006 and 2017. Serologic markers for HBV (HBsAg, anti-HBs, anti-HBc) were performed prior and during biologic treatment. Patients with chronic or resolved infection were monitored every 3 months. RESULTS: The prevalence of HBV in our cohort was 15.7% (chronic infection: 0.4%, resolved infection: 12.6%, anti-HBc positivity alone: 2.6%). 12 (6.2%) out of 191 HBV infected patients experienced a reactivation. All of them showed markers of past infection. One patient experienced HBV reactivation despite lamivudine. Only one patient experienced acute hepatitis, probably due to the interruption of immunosuppressors in anticipation of surgery, not preceded by any HBV prophylactic treatment. CONCLUSIONS: HBV reactivation is a rare event in patients treated with a bDMARD and it can also occur while taking lamivudine, not only in chronic carriers (as per the literature data) but also in inactive ones. Regular screening followed by prompt treatment can prevent symptoms or complications. Due to the risk of hepatitis following the immune reconstitution, an antiviral therapy should be considered in the case of sudden discontinuation of csDMARDs or bDMARD.

Alveolar haemorrhage in ANCA-associated vasculitis: Long-term outcome and mortality predictors.

INTRODUCTION: Alveolar haemorrhage (AH) is considered an important cause of morbidity and early mortality in anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV). OBJECTIVES: The aim of this study was to identify predictors of outcome in patients with AH-AAV and to evaluate outcome and causes of death in this subset. MATERIALS AND METHODS: A multicenter retrospective study was conducted in 29 Italian Centers. Clinicians were asked to recruit all patients diagnosed with AAV-associated AH during the last 10 years, from 2007 to 2016. Univariate and multivariable analysis were performed. RESULTS: One-hundred and six patients were included (median age at onset of 55 years [IQR 42-67]). The majority were ANCA-positive (PR3 57.1%, MPO 33.7%) and 72.6% had also renal involvement. At presentation, anaemia was shown in 97 (92.4%) patients, hemoptysis in 54 (51.9%), respiratory failure in 68 (66.7%), of whom 48 (70.6%), requiring respiratory support. At the end of the 37 months [IQR 13-77] follow-up, 19/106 (17.9%) patients were dead. The main causes of death were active disease and infections. By stepwise regression analysis, age >65 years (HR 3.66 [95% CI 1.4-9.51], p = 0.008) and the need for respiratory support (HR 4.58 [95% CI 1.51-13.87], p = 0.007) at AH onset were confirmed to be predictive of mortality. CONCLUSIONS: Predictors of outcome in AAV-AH were determined. Factors related to the patient's performance status and the severity of the lung involvement strongly influenced the outcome. Balancing harms and benefits for the individual patient in induction and maintenance treatment strategies is crucial.

Risk factors of suspected spondyloarthritis among inflammatory bowel disease patients.

Background: Occurring in approximately 20-30% of patients, spondyloarthritis is the most common extraintestinal manifestation in inflammatory bowel disease (IBD).Aims: To look for risk factors of spondyloarthritis among inflammatory bowel disease patients.Methods: We modified the STRIPP questionnaire created for psoriatic patients and we created a rapid questionnaire for rheumatologic investigation in IBD patients (STRII). We submitted the questionnaire to all consecutive patients with a known spondyloarthritis in our centre and to patients with a negative rheumatological diagnosis to find the cut-off value. Finally, we prospectively submitted the STRII questionnaire to all consecutive IBD patients in our centre.Results: A cut-off ≥3 correlated with spondyloarthritis with an AUC = 0.91. The STRII questionnaire was submitted to 1147 IBD patients. Two hundred and forty-four out of 1147 (21.3%) collected a STRII score of ≥3. Female sex (p < .0001) and Crohn's disease (p = .023) were risk factors. Patients with a history of at least 1 immunosuppressant or biologic drug (p = .002 and p < .0001, respectively) had a higher rate of positivity to STRII questionnaire.Conclusion: Among IBD patients, females, Crohn's disease, those with a history of at least 1 immunosuppressive or biological therapy are at increased risk of spondyloarthritis.

The Immunogenicity of Branded and Biosimilar Infliximab in Rheumatoid Arthritis According to Th9-Related Responses.

Our objective was to evaluate the immunogenicity of branded and biosimilar infliximab by detecting changes in T-helper-9 (Th9) percentages induced by an in vitro stimulation test. METHODS: Peripheral blood mononuclear cells collected from 55 consecutive rheumatoid arthritis (RA) outpatients (15 drug free, 20 successfully treated with branded infliximab, 20 branded infliximab inadequate responders) and 10 healthy controls were cultured, with or without 50 µg/mL of infliximab originator (Remicade®) or 50 µg/mL of infliximab biosimilar (Remsima®) for 18 h. Th9 lymphocytes were identified by means of flow cytometry as PU.1 and IRF4-expressing, IL-9-secreting CD4⁺ T cells. Furthermore, the markers CCR7 and CD45RA were used to distinguish naïve from memory IL-9 producer cells. RESULTS: Under unstimulated conditions, the drug-free RA patients had the highest percentages of Th9 lymphocytes. Following stimulation with branded infliximab, the percentages of PU.1 and IRF4-expressing Th9 cells, CCR7⁺, CD45RA- (central memory) and CCR7-, CD45RA- (effector memory) cells significantly increased in the group of inadequate responders, but no significant variation was observed after exposure to the biosimilar of infliximab. CONCLUSIONS: Th9 cells seem to be involved in the immune response to the epitopes of branded, but not biosimilar, infliximab, and this may depend on the recall and stimulation of both central and effector memory cells.

Psoriatic Arthritis Registries.

The introduction of new biological drugs for the treatment of rheumatoid arthritis and spondyloarthritis has led to the creation of a number of registries in Europe and the United States. Most of them are sponsored by national rheumatology societies, and provide information that is useful in clinical practice concerning the clinical characteristics, efficacy, and safety of all licensed biological drugs. Their findings also help to improve our understanding of the quality of life and working ability of patients receiving biological drugs, and suggest methods for allocating resources. However, there are only a few registries for psoriatic arthritis, and efforts should be made to increase their number to obtain further reliable and useful data.

Standard and pocket-size lung ultrasound devices can detect interstitial lung disease in rheumatoid arthritis patients.

OBJECTIVES: Interstitial lung disease (ILD) is a frequent extra-articular manifestation of RA associated with increased mortality. High-resolution CT (HRCT) is used for diagnosis and follow-up, but its accuracy is counterbalanced by high costs and radiological risk. In the presence of ILD, lung US (LUS) detects vertical artefacts called B-lines. The aims of the present study were to evaluate the accuracy of LUS in the diagnosis of ILD in RA and to validate the use of a pocket-size US device (PS-USD) as a screening tool. METHODS: LUS was performed with standard equipment by a trained physician through longitudinal scans following anatomical lines: 72 segments were considered (28 anteriorly and 44 posteriorly) and B-lines were counted in each segment. A B-lines score >10 identified a positive examination (presence of ILD). A second LUS session for positive/negative judgment was performed by a short-trained physician using a PS-USD. RESULTS: Thirty-nine patients were studied. The sensitivity and specificity of standard LUS vs HRCT were 92% and 56%, respectively. The B-line score was significantly correlated with HRCT score (r = 0.806). A total of 29 patients were studied with a PS-USD. Sensitivity and specificity for PS-USD vs HRCT were 89% and 50%. CONCLUSION: The sensitivity of LUS in the detection of ILD supports its use as a screening test for ILD in RA patients, even in the ambulatory setting with a PS-USD. The strong correlation between echographic and HRCT scores indicates LUS is a valid tool for grading and follow-up of ILD.

Efficacy and Safety of Upadacitinib in Rheumatoid Arthritis: Real-Life Experience from a Prospective Longitudinal Multicentric Study.

BACKGROUND: We provide the first prospective longitudinal multicenter experience on Upadacitinib efficacy and safety profile in Rheumatoid Arthritis (RA) in a real-life context, focusing on clinimetric and ultrasonographic (US) data. METHODS: RA patients referred to three Italian tertiary Centers who started Upadacitinib were enrolled as per ACR/EULAR classification criteria and prospectively reviewed. The primary aim of this study was to assess changes in clinimetric and ultrasonographic scores through time (at baseline, after 1 month, 3 months, and 6 months from the beginning of the therapy). Secondary aims were to: (i) estimate the impact of biologic lines of treatment and concomitant therapies on response to therapy; (ii) explore changes in laboratory parameters; and (iii) find potential predictive factors associated with response to therapy. RESULTS: Seventy-one patients (49 Females and 22 Males) were included. Clinimetric scores, including the Disease Activity Score (DAS28-CRP) and Simplified Clinical Disease Activity Index (SDAI), and US findings (synovial hypertrophy and power Doppler) significantly improved (p = 0.029, p = 0.001, p = 0.001, p = 0.001, respectively). Regression analysis revealed a significant association between the concomitant csDMARDs therapy at baseline and the lack of improvement in synovial hypertrophy [OR -4.824, p = 0.010] as well as with DAS28-CRP [OR -0.690, p = 0.045], whereas the presence of increased ESR or CRP at baseline was able to predict a significant improvement in SDAI [OR 8.481, p = 0.003]. No adverse events, such as deep venous thrombosis, pulmonary embolism, or herpes zoster virus infection, were reported during this study observation. CONCLUSION: Our real-life experience confirms the efficacy of Upadacitinib in terms of clinical and ultrasonographic improvement, as well as displaying a good safety profile.

Influence of Safety Warnings on the Prescribing Attitude of JAK Inhibitors for Rheumatoid Arthritis in Italy.

Background/Objectives: The Janus kinase inhibitors (JAKi) tofacitinib (TOFA), baricitinib (BARI), upadacitinib (UPA), and filgotinib (FILGO) are effective drugs for the treatment of rheumatoid arthritis. However, the US Food and Drug Administration (FDA) raised concerns about the safety of TOFA after its approval. This prompted the European Medicines Agency (EMA) to issue two safety warnings for limiting TOFA use, then extended a third warning to all JAKi in patients at high risk of developing serious adverse effects (SAE). These include thrombosis, major adverse cardiac events (MACE), and cancer. The purpose of this work was to analyze how the first two safety warnings from the EMA affected the prescribing of JAKi by rheumatologists in Italy. Methods: All patients with rheumatoid arthritis who had been prescribed JAKi for the first time in a 36-month period from 1 July 2019, to 30 June 2022 were considered. Data were obtained from the medical records of 29 Italian tertiary referral rheumatology centers. Patients were divided into three groups of 4 months each, depending on whether the JAKi prescription had occurred before the EMA's first safety alert (1 July-31 October 2019, Group 1), between the first and second alerts (1 November 2019-29 February 2020, Group 2), or between the second and third alerts (1 March 2021-30 June 2021, Group 3). The percentages and absolute changes in the patients prescribed the individual JAKi were analyzed. Differences among the three groups of patients regarding demographic and clinical characteristics were also assessed. Results: A total of 864 patients were prescribed a JAKi during the entire period considered. Of these, 343 were identified in Group 1, 233 in Group 2, and 288 in Group 3. An absolute reduction of 32% was observed in the number of patients prescribed a JAKi between Group 1 and Group 2 and 16% between Group 1 and Group 3. In contrast, there was a 19% increase in the prescription of a JAKi in patients between Group 2 and Group 3. In the first group, BARI was the most prescribed drug (227 prescriptions, 66.2% of the total), followed by TOFA (115, 33.5%) and UPA (1, 0.3%). In the second group, the most prescribed JAKi was BARI (147, 63.1%), followed by TOFA (65, 27.9%) and UPA (33, 11.5%). In the third group, BARI was still the most prescribed JAKi (104 prescriptions, 36.1%), followed by UPA (89, 30.9%), FILGO (89, 21.5%), and TOFA (33, 11.5%). The number of patients prescribed TOFA decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). The number of patients who were prescribed BARI decreased significantly between Group 1 and Group 2 and between Group 2 and Group 3 (p ˂ 0.01). In contrast, the number of patients prescribed UPA increased between Group 2 and Group 3 (p ˂ 0.01). Conclusions: These data suggest that the warnings issued for TOFA were followed by a reduction in total JAKi prescriptions. However, the more selective JAKi (UPA and FILGO) were perceived by prescribers as favorable in terms of the risk/benefit ratio, and their use gradually increased at the expense of the other molecules.

Management of Patients Affected by Giant Cell Arteritis during the COVID-19 Pandemic: Telemedicine Protocol TELEMACOV.

Giant cell arteritis (GCA) is the most common primary systemic vasculitis in western countries, prevalently affecting elderly people. Both early diagnosis and regular monitoring are necessary for the correct management of GCA. Following the outbreak of the COVID-19 pandemic, government decisions aiming at reducing the contagion led to reductions in health activities, limiting them to urgent cases. At the same time, remote monitoring activities have been implemented through telephone contacts or video calls carried out by specialists. In line with these deep changes affecting the worldwide healthcare system and in consideration of the high risk of GCA morbidity, we activated the TELEMACOV protocol (TELEmedicine and Management of the patient affected by GCA during the COVID-19 pandemic) in order to remotely monitor patients affected by GCA. The aim of this study was to evaluate the effectiveness of telemedicine in the follow-up of patients already diagnosed with GCA. This was a monocenter observational study. Patients with a previous diagnosis of GCA admitted to the Rheumatology Unit of the University Hospital "Città della Salute e della Scienza" in Turin were monitored every 6-7 weeks by means of video/phone calls from 9 March to 9 June 2020. All patients were asked questions concerning the onset of new symptoms or their recurrence, exams carried out, changes in current therapy, and satisfaction with video/phone calls. We performed 74 remote monitoring visits in 37 GCA patients. Patients were mostly women (77.8%) and had a mean age of 71.85 ± 9.25 years old. The mean disease duration was 5.3 ± 2.3 months. A total of 19 patients received oral glucocorticoids (GC) alone at the time of diagnosis with a daily dose of 0.8-1 mg/kg (52.7 ± 18.3 mg) of prednisone, while 18 patients were treated with a combination of oral steroids (at the time of diagnosis, the prednisone mean dose was 51.7 ± 18.8 mg) and subcutaneous injections of tocilizumab (TCZ). During the follow-up, patients additionally treated with TCZ reduced their GC dose more than patients treated with GC alone (p = 0.03). Only one patient, who was treated with GC alone, had a cranial flare and needed to increase the dosage of GC, which led to rapid improvement. Furthermore, all patients proved very adherent to the therapies (assessed by Medication Adherence Rating Scale (MARS)) and considered this type of monitoring very satisfactory according to a Likert scale (mean score 4.4 ± 0.2 on a 1-5 range). Our study shows that telemedicine can be safely and effectively used in patients with GCA under control as a possible alternative, at least for a limited period of time, to traditional visits.

New Onset of Giant Cell Arteritis following ChAdOx1-S (Vaxevria®) Vaccine Administration.

We report a 78-year-old man presenting with persistent headaches in vertex and temporo-parietal area; fatigue, worsening after walking; jaw claudication; scotomas; pharyngodynia; and dry cough after the second dose of the SARS-CoV-2 vaccine (ChAdOx1-S) administration. Laboratory findings showed an elevated C-reactive protein level and FDG-CT PET showed evidence of active large vessel vasculitis with diffuse abnormal artery uptake. Under suspicion of vasculitis, a temporal arteries biopsy was performed; the histopathologic findings demonstrated the transmural inflammatory infiltrate with giant cells, compatible with giant cell arteritis. Although the overall incidence of vaccine-triggered autoimmunity is low, rheumatologists worldwide should be aware of autoimmune diseases as a new potential adverse event of vaccines.

Predictors of DAPSA Response in Psoriatic Arthritis Patients Treated with Apremilast in a Retrospective Observational Multi-Centric Study.

BACKGROUND: To date, only a few real-world-setting studies evaluated apremilast effectiveness in psoriatic arthritis (PsA). The aims of this retrospective observational study are to report long-term Disease Activity Index for Psoriatic Arthritis (DAPSA) response of apremilast in PsA patients and to analyze the predictors of clinical response. METHODS: All PsA consecutive patients treated with apremilast in fifteen Italian rheumatological referral centers were enrolled. Anamnestic data, treatment history, and PsA disease activity (DAPSA) at baseline, 6 months, and 12 months were recorded. The Mann-Whitney test and chi-squared tests assessed the differences between independent groups, whereas the Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. Logistic regressions verified if there were factors associated with achievement of DAPSA low disease activity or remission at 6 and 12 months. RESULTS: DAPSA low disease activity or remission rates at 6 and 12 months were observed, respectively, in 42.7% (n = 125) and 54.9% (n = 161) patients. Baseline DAPSA was inversely associated with the odds of achieving low disease activity or remission at 6 months (odds ratio (OR) 0.841, 95% confidence interval (CI) 0.804-0.879; p < 0.01) and at 12 months (OR 0.911, 95% CI 0.883-0.939; p < 0.01). CONCLUSIONS: Almost half of the PsA patients receiving apremilast achieved DAPSA low disease activity or remission at 6 and 12 months. The only factor associated with achievement of low disease activity or remission at both 6 and 12 months was baseline DAPSA.

Therapeutic Effects of Apremilast on Enthesitis and Dactylitis in Real Clinical Setting: An Italian Multicenter Study.

INTRODUCTION: Enthesitis and dactylitis are difficult-to-treat features of psoriatic arthritis (PsA), leading to disability and affecting quality of life. OBJECTIVE: The aim of this study is to evaluate enthesitis (using the Leed enthesitis index (LEI)) and dactylitis at 6 and 12 months in patients treated with apremilast. METHODS: Patients affected by PsA from fifteen Italian rheumatological referral centers were screened. The inclusion criteria were: (a) enthesitis or dactylitisphenotype; (b) treatment with apremilast 30 mg bid. Clinical and treatment history, including PsA disease activity, were recorded. Mann-Whitney and chi-squared tests were used to assess the differences between independent groups, and Wilcoxon matched pairs signed-rank test assessed the differences between dependent samples. A p-value of <0.05 was considered statistically significant. RESULTS: The Eph cohort consisted of 118 patients (median LEI 3); the Dph cohort included 96 patients with a median dactylitis of 1 (IQR 1-2). According to an intention to treat analysis, 25% and 34% of patients with enthesitis achieved remission (i.e., LEI = 0) in T1 and T2. The remission of dactylitis was 47% in T1 and 44% in T2. The per protocol analysis (patients observed for at least 12 months) showed that both dactylitis and LEI significantly improved in T1 (median LEI 1 (IQR 1-3)) and T2 (median LEI 0 (IQR 1-2)). CONCLUSION: Eph and Dph PsA patients treated with apremilast experienced a significant improvement in enthesitis and dactylitis activity. After 1 year, enthesitis and dactylitis remission was achieved in more than one-third of patients.

Effectiveness of SB4 Transition from Originator Etanercept in Rheumatoid Arthritis and Axial Spondyloarthritis: A Subgroup Analysis from the BENEFIT Study.

Objectives: The pan-European BENEFIT study of patients with stable rheumatoid arthritis (RA) or axial spondyloarthritis (axSpA) who transitioned from reference etanercept to SB4 found no clinically meaningful changes in disease control after transition. The analysis aims to illustrate the peculiarities of the Italian cohort of patients compared with the whole population to provide a more real-life approach to the data for the Italian rheumatologists, ruling out possible local confounding factors. Methods: A prospective study for up to 6 months following transition was conducted. Outcome measures of interest include clinical characteristics at time of transition and disease activity scores (Disease Activity Score-28 [DAS28] for RA, Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] for axSpA) over time and safety. Results: One-hundred and eleven subjects (out of the 557 in total enrolled in the study) were derived from 8 Italian sites, including 79 with RA and 32 with axSpA. In both cohorts, the efficacy was maintained at 3 months and 6 months from the transition to the biosimilar with no significant change in mean DAS28 and BASDAI scores: at the end of the 6 months of observation the mean DAS28 and BASDAI was similar to baseline (confidence interval [CI] -0.22, 0.22), while the mean variation of the BASDAI was -0.14. Of note, 100.0% (95% CI 89.1, 100.0) in the axSpA and 90.8% (95% CI 81.5, 95.5) in the RA cohort of patients continued to receive SB4 at month 6 (binary variable with 95% Clopper-Pearson CI). Conclusions: Italian patients with stable RA or axSpA who transitioned from originator Etanercept to SB4 maintained clinical response at 6 months post-transition. Both the cohorts are representative of typical patients with long-standing established diagnoses. Most of the patients transitioned to the same dose regimen of biosimilar as that received for the originator, and the regimen remained unchanged at 6 months, supporting the effectiveness of the transition.

Adalimumab and ABP 501 in the Treatment of a Large Cohort of Patients with Inflammatory Arthritis: A Real Life Retrospective Analysis.

The recent introduction of ABP 501, an adalimumab biosimilar, in the treatment of rheumatic diseases was supported by a comprehensive comparability exercise with its originator. On the other hand, observational studies comparing adalimumab and ABP 501 in inflammatory arthritis are still lacking. The main aim of this study is to compare the clinical outcomes of the treatment with adalimumab, both the originator and ABP 501, in a large cohort of patients affected by autoimmune arthritis in a real life setting. We retrospectively analysed the baseline characteristics and the retention rate in a cohort of patients who received at least a course of adalimumab (originator or ABP 501) from January 2003 to December 2020. We stratified the study population according to adalimumab use: naive to original (oADA), naive to ABP 501 (bADA) and switched from original to ABP 501 (sADA). The oADA, bADA and sADA groups included, respectively, 724, 129 and 193 patients. In each group, the majority of patients had a diagnosis of rheumatoid arthritis. The total observation period was 9805.6 patient-months. The 18-month retentions rate in oADA, bADA and sADA was, respectively, 81.5%, 84.0% and 88.0% (p > 0.05). The factors influencing the adalimumab retention rate were an axial spondylarthritis diagnosis (Hazard Ratio (HR) 0.70; p = 0.04), switch from oADA to ABP 501 (HR 0.53; p = 0.02) and year of prescription (HR 1.04; p = 0.04). In this retrospective study, patients naive to the adalimumab originator and its biosimilar ABP 501 showed the same retention rate. Patients switching from the originator to biosimilar had a higher retention rate, even though not statistically significant, when compared to naive.

Efficacy and Drug Survival after Switching from Etanercept to the Biosimilar SB4: A Real-Life Long-Term Study.

We evaluated the 3-year drug survival and efficacy of the biosimilar SB4/Benepali in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients, previously treated with etanercept (ETA). Drug survival rate was calculated using the Kaplan-Meier method and Cox proportional hazard models were developed to examine predictors of SB4 discontinuation. 236 patients (120 RA, 80 PsA and 36 AS), aged 60.7 ± 13.8 years and with an ETA duration of 4.1 ± 3.4 years were included. The 3-year retention rate for SB4 was 94.4%, 88% and 86% in AS, RA and PsA patients, respectively, with no difference between groups. Patients without comorbid disease had higher retention rates vs. patients with comorbid disease (90% vs. 60%, p < 0.0001). Disease activity, as measured by DAS28, DAPSA and BASDAI remained stable over the 3 years. Comorbid disease (hazard ratio; HR: 4.06, p < 0.0001) and HAQ at baseline (HR: 2.42, p = 0.0024) significantly increased the risk of SB4 discontinuation, while previous ETA duration was negatively associated with SB4 discontinuation (HR: 0.97, p = 0.0064). Forty-one (17.4%) patients left the study due to the interruption of the SB4 treatment, 31 (75.6%) discontinued due to inefficacy and 10 (24.4%) due to adverse events. This real-life study confirms the similar efficacy profile of ETA with long-term retention and a good safety profile in inflammatory arthritis patients.

Rheumatic manifestations in inflammatory bowel disease.

Rheumatic manifestations are the most frequent extra-intestinal manifestations (EIMs) in inflammatory bowel disease (IBD) patients, and they are responsible for a relevant reduction of quality of life. IBD is associated with a variety of musculoskeletal manifestations such as arthritis and non-inflammatory pain as well as with metabolic diseases, such as osteoporosis. Different imaging techniques (primarily ultrasound, magnetic resonance imaging and X-rays) can help the clinician to correctly identify the nature of manifestations and to treat the patient accordingly. Nowadays, in the setting of IBD-related arthritides, different drugs are available and can be effective on both articular and intestinal involvement. Therefore, a multi-disciplinary approach provides an early diagnosis and a better clinical outcome that can only be given from the recognition and consideration of the different EIMs. As for rheumatic manifestations, namely IBD-related arthritis, an early intervention allows to control disease activity and to prevent structural damage.

Autoantibodies and Rheumatologic Manifestations in Hepatitis C Virus Infection.

HCV is a virus that can cause chronic infection which can result in a systemic disease that may include many rheumatologic manifestations such as arthritis, myalgia, sicca syndrome, cryoglobulinemia vasculitis as well as other non-rheumatological disorders (renal failure, onco-haematological malignancies). In this population, the high frequency of rheumatoid factor (45-70%), antinuclear (10-40%) and anticardiolipin (15-20%) antibodies is a B-cell mediated finding sustained by the infection. However, the possibility that a primitive rheumatic pathology may coexist with the HCV infection is not to be excluded thus complicating a differential diagnosis between primitive and HCV-related disorders.