Comorbidities in the Spondyloarthritis GISEA Cohort: an average treatment effect analysis on patients treated with bDMARDs.

OBJECTIVES: We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis. METHODS: SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance. RESULTS: The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities. CONCLUSIONS: Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.

Prevalence and management of tuberculosis infection in Apulian rheumatologic patients treated with biologics: An observational cohort 10-year study from the BIOPURE registry.

INTRODUCTION: The objective of this study was to assess the 10-year prevalence of latent tuberculosis infection (LTBI) among Apulian patients with rheumatic diseases (RDs). Secondary endpoint was to record new cases of active TB disease and LTBI among patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs). METHODS: We analysed the results from the patients included in the BIOPURE registry from 2009 to 2018, who underwent QuantiFERON-TB Gold In-tube (QFT-GIT) test as screening before bDMARDs treatment. Demographic and clinical data were recorded at the time of the first QFT-GIT test. Administration of preventive therapy and bDMARD treatments were recorded for patients with positive QFT-GIT test. All new tuberculosis infections were recorded during the follow-up. RESULTS: The final study population included 3028 patients (855 rheumatoid arthritis, 1001 psoriatic arthritis, 833 spondyloarthritis, 130 connective tissue diseases, 33 systemic vasculitis and 176 other inflammatory rheumatic conditions), more frequently female (67.2%), with a mean age of 52 ± 18 years. Patients with QFT-GIT-positive test were elderly people, predominantly male with higher prevalence of diabetes as comorbidity. The 10-year prevalence of LTBI was 10.8%. Of note, no cases of TB reactivation were recorded in patients who completed preventive therapy treatment. Three thousand and sixteen patients were followed over time (42.6 ± 30 months), and five (.2%) developed active TB, which corresponds to .47 cases per 1000 person-years. CONCLUSIONS: In the 10-year observation, the use of bDMARDs seems to be safe in rheumatologic patients with positive QFT-GIT test treated according to current recommendations. Nevertheless, cases of primary TB disease did occur during treatment with biologicals.

Effectiveness of Golimumab as Second Anti-TNFα Drug in Patients with Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondyloarthritis in Italy: GO-BEYOND, a Prospective Real-World Observational Study.

In this prospective observational study, data were collected from 34 rheumatology clinics in Italy in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) who started golimumab (GLM) as a second anti-TNFα drug. The primary objective was to evaluate the effectiveness of GLM after 6 months. Changes in quality of life using the EQ-5D-5L were also assessed. A total of 194 patients aged 53.2 ± 12 years started GLM as a second anti-TNF drug: 39 (20.1%) with RA, 91 (46.9%) with PsA and 64 (32.9%) with axSpA. After 6 months of GLM treatment, 68% of RA patients achieved low disease activity (LDA; DAS28-CRP ≤ 3.2), 31.9% of PsA patients achieved minimal disease activity and 32.5% of axSpA patients achieved LDA (ASDAS-CRP < 2.1). Good/moderate EULAR response was achieved in 61.9% and 73.8% of patients with RA and PsA, respectively, and 16% of axSpA patients achieved a 50% improvement in BASDAI. Across all indications, improvements in disease activity measures and EQ-5D-5L domains were observed over 6 months. The main reasons for GLM interruption were lack/loss of efficacy (7.2%) or adverse events (2%). This study confirms the effectiveness of GLM as a second-line anti-TNF for the treatment of RA, PsA and axSpA in a real-world setting in Italy.

Effectiveness and safety of secukinumab in 608 patients with psoriatic arthritis in real life: a 24-month prospective, multicentre study.

OBJECTIVES: To evaluate in a multicentric Italian cohort of patients with psoriatic arthritis (PsA) on secukinumab followed for 24 months: (1) the long-term effectiveness and safety of secukinumab, (2) the drug retention rate and minimal disease activity (MDA), (3) differences in the outcomes according to the biological treatment line: biologic-naïve patients (group A) versus multifailure (group B) patients. METHODS: Consecutive patients with PsA receiving secukinumab were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical values were recorded at baseline (T0), 6(T6), 12(T12) and 24(T24) months. Effectiveness was evaluated overtime with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and MDA at T6. Infections and adverse events were recorded. RESULTS: 608 patients (41.28% men; mean (SD) age 52.78 (11.33)) were enrolled; secukinumab was prescribed as first-line biological treatment in 227 (37.34%) patients, as second (or more)-line biological treatment in 381 (62.66%). Effectiveness of secukinumab was shown with an improvement in several outcomes, such as Ankylosing Spondylitis Disease Activity Score (T0=3.26 (0.88) vs T24=1.60 (0.69) ;p=0.02) and Disease Activity Index for Psoriatic Arthritis (T0=25.29 (11.14) vs T24=7.69 (4.51); p<0.01). At T24, group A showed lower Psoriasis Area Severity Index (p=0.04), erythrocyte sedimentation rate and C reactive protein (p=0.03 ;p=0.05) and joint count (p=0.03) compared with group B. At T24, MDA was achieved in 75.71% of group A and 70.37% of group B. Treatment was discontinued in 123 (20.23%) patients, mainly due to primary/secondary loss of effectiveness, and in 22 due to adverse events. Retention rate at T24 was 71% in the whole population, with some difference depending on secukinumab dosage (p=0.004) and gender (p=0.05). CONCLUSIONS: In a real-life clinical setting, secukimumab proved safe and effective in all PsA domains, with notable drug retention rate.

Retrospective evaluation of patient profiling and effectiveness of apremilast in an Italian multicentric cohort of psoriatic arthritis patients.

OBJECTIVES: We aimed to evaluate the baseline characteristics, the reasons for prescription, and the effectiveness/safety profile of real-life apremilast for the treatment of psoriatic arthritis (PsA). METHODS: PsA patients treated with apremilast were retrospectively extracted from an Italian multicentric cohort. Baseline population characteristics and reasons for apremilast prescription were analysed. Clinical response was defined as the proportion of patients achieving Disease Activity in PSoriatic Arthritis (DAPSA) remission/low disease activity (LDA), minimal disease activity (MDA), and very low disease activity (VLDA). Six-month retention rate was computed by the Kaplan-Meier method, with a detailed analysis of reasons for discontinuation. Univariate and multivariate models were developed to examine predictors of clinical response and persistence. RESULTS: The study population included 131 patients mainly with oligoarticular PsA (58%), carrying at least one comorbidity (64.1%, in particular history of malignancies [25.9%] and latent tuberculosis [16.3%]) treated with apremilast as first-line targeted therapy (47.7%) or in biologics failures (52.3%). Contraindication to biologics (60.3%) and lack of poor prognostic factors (27.5%) were the most frequent reason for apremilast prescription. The 6-month retention rate was 72.1%. Inefficacy (n=7), diarrhoea (n=10), nausea (n=3), and headache (n=7) were the most frequent reasons for discontinuation. At 3 months DAPSA LDA/remission, MDA, and VLDA were observed in 40.3, 6.7, and 5.6% of patients, respectively. Female sex was a negative predictor of both retention rate and clinical response. CONCLUSIONS: In our real-life analysis apremilast was mainly used in oligoarticular PsA carrying comorbidities leading to contraindications to biologics. Effectiveness and safety profiles were consistent with clinical trials.

Effectiveness of Certolizumab-Pegol in Rheumatoid Arthritis, Spondyloarthritis, and Psoriatic Arthritis Based on the BIOPURE Registry: Can Early Response Predict Late Outcomes?

BACKGROUND: Identification of predictors of clinical response to certolizumab-pegol (certolizumab) may aid the decision-making process for treating patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). OBJECTIVE: The aim of our study was to evaluate the effectiveness of certolizumab and identify any predictors of favorable outcome in patients with RA, PsA, or SpA. METHODS: We studied 355 RA, SpA, and PsA patients starting treatment with certolizumab. Endpoints of the study were drug survival and identification of predictors of clinical outcome. Drug retention was analyzed via the Kaplan-Meier method, and hazard ratios (HRs) were estimated using Cox regression models. RESULTS: Of 355 certolizumab initiators, 178 had RA, 94 had PsA, and 83 had SpA. Biologic-naïve RA patients had significantly higher survival rates (73.3%) than switchers taking certolizumab as a second-line (49.0%) or third- or next-line biologic agent (51.2%; p = 0.0001). Instead, PsA and SpA patients showed similar drug retention rates regardless of the line of treatment. A significant clinical improvement from baseline was seen at 3 months for RA (28 joint-Disease Activity Score [DAS28]; p = 0.001), PsA (Disease Activity Index for PsA [DAPSA]; p = 0.001), and SpA (Bath Ankylosing Disease Index; p = 0.01). Biologic-naïve patients had the lowest HR (0.31; p = 0.001) of discontinuing certolizumab for RA, and the highest HR (7.94; p = 0.01) of achieving minimal disease activity (MDA) for PsA. For PsA, a predictor of late MDA was the achievement of low/remission DAPSA at 3 months, and 3-month low/remission DAS28 predicted late remission for RA. CONCLUSIONS: Our study revealed that the best predictor of certolizumab effectiveness in unselected patients with RA, PsA, or SpA was a biologic-naïve status and achievement of an early response within 3 months.

Switch or swap strategy in rheumatoid arthritis patients failing TNF inhibitors? Results of a modified Italian Expert Consensus.

Objective: To establish evidence-based and experts' opinion filtered statements on the optimal treatment choice between cycling (switch) and changing mode of action strategies (swap) in RA patients failing TNF inhibitors (TNFis). Methods: The relevant question (switch vs swap) was rephrased into a research question according to the population, intervention, comparison and outcome (PICO) strategy, considering all the available scientific evidence published from the 2013 EULAR set of recommendations up to mid-January 2016. Final statements derived from the retrieved scientific evidence and experts' consensus, with eventual rephrasing through a Delphi method during a national consensus of Italian rheumatologists. Results: From a total of 365 records, 12 studies were finally included. The final statements argued that, until head-to-head comparison data are available, switch and swap can be still considered suitable strategies in RA patients failing first TNFi, even though some data seem to lend more support to a different mode of action-targeted strategy. Conclusion: After failure of first TNFi course, switch and swap can be currently considered as alternative suitable approaches in RA patients.

Correction to: Drug survival and effectiveness of ustekinumab in patients with psoriatic arthritis. Real-life data from the biologic Apulian registry (BIOPURE).

In Fig. 1 - paned D, incorrect image was published. This is now presented correctly in this article.

Drug survival and effectiveness of ustekinumab in patients with psoriatic arthritis. Real-life data from the biologic Apulian registry (BIOPURE).

This study aims to evaluate the drug survival and effectiveness of ustekinumab in psoriatic arthritis (PsA) patients naïve to biologics or inadequate responders to tumor necrosis factor (TNF-IR) inhibitors in real life. PsA patients starting ustekinumab were enrolled from 2014 to 2016. Joint involvement, peripheral or axial, Psoriatic Area Severity Index, Disease Activity Psoriatic Arthritis (DAPSA), Lee Enthesitis Index, Health Assessment Questionnaire, body mass index, comorbidities, co-therapies, mechanism of action, and causes of discontinuation of prior TNFi were collected at baseline, and 6 and 12 months. Twelve-month drug survival was evaluated by Kaplan-Meier curves. Hazard ratios (HRs) of drug discontinuation adjusted for baseline factors were estimated by multiple Cox regression analysis. Percentages of DAPSA-based remission, as crude value and adjusted for drug retention (LUNDEX index), were compared by χ2 test. Mean differences of DAPSA from baseline to 6 and 12 months were compared between naïve and TNF-IR patients by ANOVA. Of 160 PsA patients starting ustekinumab, 54 were naïve and 106 were TNF-IR. Twelve-month drug survival was significantly higher in naïve (87%) than in TNF-IR (68%, p = 0.01). Baseline co-therapy with methotrexate did not increase the persistence on ustekinumab. Naïve patients had the lowest risk of ustekinumab discontinuation (HR 0.27, p = 0.01), and the highest DAPSA-based remission (34%, LUNDEX 26%). Mean differences from baseline of DAPSA was significantly greater in naïve than in TNF-IR patients at 12 months (- 14.4 ± 10 vs. - 4.1 ± 17, p = 0.01). Our data showed that ustekinumab has a good effectiveness in real life and the best outcomes are achieved in biologic-naïve PsA patients.

Golimumab in real-life settings: 2 Years drug survival and predictors of clinical outcomes in rheumatoid arthritis, spondyloarthritis, and psoriatic arthritis.

OBJECTIVES: To assess the drug survival of golimumab, and predictors thereof, in patients affected with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) in a prospective observational cohort. METHODS: This is a non-interventional, longitudinal study on RA, SpA, and PsA patients starting treatment with golimumab. Endpoints were the 2 years persistence rate of golimumab and predictors of therapy discontinuation. Drug retention was analyzed using Kaplan-Meier and Cox models. Hazard ratios (HR) of golimumab discontinuation were estimated by Cox-regression hazard models. RESULTS: Of 416 patients starting golimumab, 171 biologic-naïve and 245 inadequate responders to prior biologic drugs, 88 had RA, 147 SpA, and 181 PsA. Global 2 years drug retention was 70.2%, with no different hazard of discontinuation among diseases or line of biologic treatment. The strongest predictor of golimumab discontinuation was female gender (HR = 1.95). Golimumab monotherapy was associated with higher risk drug interruption (HR = 1.67). Within SpA, predictors of golimumab discontinuation were female sex (HR = 4.19), and absence of extra-articular manifestations (HR = 4.60). In PsA, duration of disease was negatively associated to drug interruption (HR = 0.93), whereas golimumab monotherapy was positively (HR = 2.21) associated. Interestingly, failing to achieve a good EULAR response at 3 months was the only predictor of golimumab discontinuation for RA patients (HR = 3.03). CONCLUSIONS: This study provided evidence that golimumab has high retention rate in real-life settings. SpA male patients with extra-articular manifestations, PsA patients on co-therapy with DMARDs, and RA patients attaining an early clinical response had the highest probability to continue golimumab over 2 years.

Use of ultrasound in treatment decisions for patients with rheumatoid arthritis: an observational study in Italy.

In rheumatoid arthritis (RA), treatment response is generally assessed using standard clinical disease activity measures. However, ultrasound has become increasingly popular among rheumatologists to monitor disease activity and response. The purpose of this analysis of ECOgraphic evaluation for STaging ARthritis (ECOSTAR) study data was to determine how ultrasound affects clinicians' decisions about changing treatment in RA. ECOSTAR was an observational, cohort study conducted between March 2010 and December 2012 at nine clinical centers in Italy in RA patients being considered for treatment change. After clinical evaluation of each patient, patients underwent diagnostic ultrasound (US) investigations and each patient was given a total echography score using a combination of scores for joint effusion, synovial hypertrophy, and power Doppler. The US results were provided to the clinicians and the influence of US on the clinicians' treatment choices were recorded. Ninety-five patients screened for study inclusion had confirmed RA (mean age 53.9 years; mean disease duration 8.9 years). Therapy changes were made by clinicians according to the hand and wrist joint US scores: score 0 appeared to have no influence on clinicians' decision to modify treatment, scores >0-3 were associated with a numerically higher estimated probability of not changing therapy than changing therapy, and scores >3 had a greater influence on the clinician to modify therapy and an increased probability of the clinician changing therapy versus not changing therapy. Ultrasonography scores appear to influence treatment decisions in patients with RA, with clinicians appearing less likely to alter treatment regimens in patients with low ultrasound scores and more likely to change treatment regimens when higher scores are obtained. Further research is warranted.