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The objective was to assess the adherence, persistence, and costs of bDMARDs through a multicentre study of nine Italian hospital pharmacies. The drugs analysed were Abatacept, Adalimumab, Certolizumab, Etanercept, Golimumab and Tocilizumab. Adult subjects with Rheumatoid Arthritis were considered in the analysis. In this study, we calculated the following metrics: Adherence to treatment was evaluated as dose-intensity, which is the ratio between the amount of medication received and probably taken by the patient at home (Received Daily Dose, RDD) and the amount prescribed by the clinician (Prescribed Daily Dose, PDD). Persistence was calculated as the number of days between the first and last dispensing of the same drug. Lastly, costs were assessed based on persistence to treatment and normalized for adherence. Adherence to treatment was found to be above 0.8 for all drugs studied. The median persistence for a 5-year treatment period was 1.4 years for Abatacept, 1.7 years for Adalimumab, 1.8 years for Certolizumab, 1.4 years for Etanercept, 1.3 years for Golimumab, and 1.6 years for Tocilizumab. This multicentre retrospective observational study of bDMARDs used in the treatment of RA showed that, for all the drugs studied, there was no problem with adherence to treatment but rather a difficulty in maintaining treatment with the same drug over time. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this economic evaluation was to compare the cost per responder between upadacitinib and abatacept (intravenous [iv] or subcutaneous [sc]) in patients with moderate-to-severe Rheumatoid Arthritis (RA) in Italy. Methods: The clinical efficacy was assessed based on SELECT-CHOICE study results. The clinical efficacy of upadacitinib and abatacept (iv or sc) was measured by Clinical Remission (CR), Low Disease Activity (LDA) and American College of Rheumatology response (ACR20, 50 and 70). The treatment cost was based on the number of administrations dispensed at 12 or 24 weeks. The cost per responder was adopted as a cost-effectiveness indicator. Results: Independent of the clinical efficacy measure used and the duration of treatment considered, the cost per responder was consistently lower for upadacitinib compared to abatacept (iv or sc) across all clinical measures. For example, considering the CR at 24 weeks, the cost per responder for upadacitinib was € 9,417 compared to € 17,817 for abatacept sc or to € 23,110 for abatacept iv. The differences in the cost per responder between upadacitinib and abatacept (iv or sc) increased when higher ACR response levels were considered. Conclusions: These results suggested that upadacitinib is a cost-effectiveness option compared to abatacept (iv or sc) from the perspective of the Italian National Health Service in patients with moderate-to-severe Rheumatoid Arthritis in Italy. [ABSTRACT FROM AUTHOR]

Objectives: EULAR recommendations do not suggest which biologic disease-modifying anti-rheumatic drug (bDMARD) should be preferred after failure of a first bDMARD in the treatment of rheumatoid arthritis (RA). In particular, few data are available regarding the effectiveness of a second-line bDMARD after failure of abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX). The aim of this study was to analyze the retention rate of a second line with tumor necrosis factor inhibitors (TNFi) or other mechanisms of action (MoAs), after the failure of either RTX, TCZ, or ABA., Methods: Two hundred and seventy-eight RA patients from the Italian GISEA registry were included in the study. RTX was the first bDMARD in 18% of patients, ABA in 45.7%, and TCZ in 36.3%, while the second bDMARD was a TNFi (group 1) in 129 patients and an agent with a different MoA (group 2) in 149., Results: During a median follow-up of 22 months (IQR 68), 129 patients discontinued their treatment; patients of group 1 discontinued the treatment more frequently than patients of group 2 (p<0.001) with retention rates of 33.6±5.7% and 63.6±4.6% after 104 weeks for group 1 and group 2, respectively (p<0.001). At multivariate analysis, the mechanism of action was the only predictor for the maintenance in therapy., Conclusions: According to our data, ABA, RTX, and TCZ seem to maintain a good retention rate also when used as a second-line therapy, suggesting their use after the failure of a non-TNFi as first-line therapy. However, specifically designed studies are needed to evaluate the more appropriate therapeutic strategies in RA, according to the first-line drug, including new targeted synthetic DMARDs. Key Points • A large proportion of rheumatoid arthritis patients fail the first biologic DMARD. • Few data are available about the efficacy of biologic DMARD after the failure of a non-TNF inhibitor. • Abatacept, rituximab, or tocilizumab seem to maintain a good retention rate after the failure of a first-course therapy with a non-TNF inhibitor., (© 2021. International League of Associations for Rheumatology (ILAR).)

Purpose: Body mass index (BMI) demonstrated to influence the clinical response to different drugs in rheumatoid arthritis (RA). The aim of this study was to investigate the role of BMI in the achievement of remission in active RA patients starting the treatment with abatacept., Methods: Data regarding 130 RA patients enrolled in the UltraSound-CLinical ARthritis Activity (US-CLARA) study were retrospectively analyzed. Patients were assessed at baseline (when starting abatacept treatment) and at 3- and 6-months. An extensive clinimetric evaluation, including a new ultrasound (US)/clinical composite disease activity index, termed US-CLARA, was performed at every timepoints. Outcome of interest of the study was the impact of BMI on the achievement of the Disease Activity Score 28-joints erythrocyte sedimentation rate (DAS28-ESR) or the ACR/EULAR Boolean remission criteria at 6 month., Results: At 6-month 26 out of 130 patients were defined as responders to abatacept. Comparing the baseline characteristics of responders to non-responders, US-CLARA showed a statistically significant difference between the two groups. The logistic regression analysis showed that the two indipendent variables, predictive of treatment response (keeping the DAS28-ESR and/or Boolean remission criteria as dependent variable), were the self-tender joint count assessment (p = 0.0412) and the ultrasound score (p = 0.0211). No other baseline variable, notably BMI, was associated to 6-month abatacept response., Conclusions: BMI does not influence the abatacept response in RA patients with active disease. During abatacept treatment, the clinical response can be achieved despite a condition of overweight or obesity., (Copyright © 2019 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: Subcutaneous (SC) abatacept (ABA) is comparable to intravenous (IV) formulation in terms of efficacy and safety profile. Our work analyzed the switch to SC formulation from IV administration in patients with rheumatoid arthritis., Methods: Fifty-one patients treated with SC ABA were included. Clinical data were obtained from clinical charts., Results: Fourteen patients relapsed and needed to return to the IV administration. Neither clinical and laboratory features nor the previous therapies were identified as risk factors for SC formulation inefficacy. Disease activity decreased after the return to IV infusions., Conclusion: SC ABA showed a risk of relapse in 27% of cases. The reinsertion of the IV administration quickly reinstated disease control.

Rheumatoid arthritis (RA) patients under immunosuppressive therapy are particularly susceptible to infections, mainly of the respiratory tract, thus vaccination may represent a strategy to reduce their incidence in this vulnerable population. In the 2009-10 influenza season, the safety and immunogenicity of co-administered non-adjuvanted seasonal and MF59-adjuvanted pandemic influenza vaccines were evaluated in this study in 30 RA patients under therapy with anti-tumour necrosis factor (TNF)-α agents or Abatacept and in 13 healthy controls (HC). Patients and HC underwent clinical and laboratory evaluation before (T0), 1 (T1) and 6 months (T2) after vaccinations. No severe adverse reactions, but a significant increase in total mild side effects in patients versus HC were observed. Both influenza vaccines fulfilled the three criteria of the Committee for Proprietary Medicinal Products (CPMP). Seroconversion rate for any viral strain in patients and HC was, respectively, 68 versus 45 for H1-A/Brisbane/59/07, 72 versus 81 for H3-A/Brisbane/10/07, 68 versus 54 for B/Brisbane/60/08 and 81 versus 54 for A/California/7/2009. A slight increase in activated interferon (IFN)-γ-, TNF-α- or interleukin (IL)-17A-secreting T cells at T1 compared to T0, followed by a reduction at T2 in both patients and HC, was registered. In conclusion, simultaneous administration of adjuvanted pandemic and non-adjuvanted seasonal influenza vaccines is safe and highly immunogenic. The largely overlapping results between patients and HC, in terms of antibody response and cytokine-producing T cells, may represent further evidence for vaccine safety and immunogenicity in RA patients on biologicals., (© 2014 British Society for Immunology.)

The objective of this study was to determine long-term effectiveness and safety of 1st biological treatment (BT) in a cohort of 301 juvenile idiopathic arthritis (JIA) patients (pts), non-responders to disease-modifying antirheumatic drugs (DMARDs), in terms of drug survival (continuation rate on therapy) and to identify the baseline predictors of treatment discontinuation. Each JIA pt enrolled in BT is prospectively assessed at the start of treatment and then every 2 months for the evaluation of safety and efficacy according to ACR-Pedi30 criteria. All clinical charts of pts who started a BT between November 1999 and July 2010 have been reviewed. Survival analysis methods suitable for competing risks were used to study time to drug discontinuation due to disease control (defined according to Wallace criteria) or failure [adverse event (AE), lack of efficacy (LaE) or loss of efficacy (LoE) according ACR-Pedi30]. A number of 301 JIA pts, non-responders or intolerant to DMARDs and treated with one or more cycles of BT, were identified. Median disease duration, from onset to the beginning of 1st BT, was 7.8 years (interquartil range 2.21-15.1). In total, there were 294 1st corses with anti-TNF agents, 5 with abatacept and 2 with anakinra. A number of 298 pts were included in the analysis for drug discontinuation (3 pts with no follow-up data after their first dose of BT were excluded). The median follow-up on treatment, before discontinuation due to every cause, was 53.7 months (range 0.45-124.45). One hundred and sixty-five pts discontinued BT: 27 due to disease control, 135 because of failure (78 AEs, 12 LaE and 45 LoE), 3 pts temporarily stopped for pregnancy. Among 135 pts who discontinued for failure, 117 switched to a 2nd BT. Among 27 pts who discontinued due to remission, 13 pts restarted on BT for relapse of disease activity (10 pts restarted with the same BT, 3 switched to a different one). Predictors of discontinuation due to AE were female gender (P=0.01) and longer disease duration (P=0.02). Predictors of discontinuation due to LaE or LoE were systemic onset and polyarthritis FR positive (vs other JIA subtypes) (P&lt;0.05) and use of mAb-anti-TNF (vs sTNFR) (P=0.02). Predictors of discontinuation due to inactive disease were male gender and shorter disease duration (P&lt;0.05). Although only few pts discontinued BT due to a complete and persistent disease control, the majority of them remained on BT for a long time, suggesting that in our cohort of JIA pts, affected by a severe long lasting refractory disease, BT was globally well tolerate and efficacious in controlling the disease.

Objectives: In the 1-year, double-blind, placebo-controlled ATTEST trial, efficacy of abatacept or infliximab versus placebo was reported in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). The current study estimated trial-based and real-life costs of abatacept and infliximab for achieving pre-defined remission or low disease activity state (LDAS)., Methods: Quantity of drug, serious adverse event (SAE) rates and time (months) in remission or LDAS were taken from ATTEST for the trial-based calculation to derive a cost per remitting/LDAS patient and a cost per patient-month in remission/LDAS. Trial-based and real-life scenarios were performed., Results: The annual trial-based costs per remitting/LDAS patient were €70.238/€37.208 for abatacept and €85.565/€46.602 for infliximab. In the first 6 months of the ATTEST trial, costs per patient-month in remission/LDAS were higher for abatacept (€11.024 and €6.018, respectively), relative to infliximab (€8.347 and €4.174, respectively). Over the full 12-month trial period cost per month in remission/LDAS estimates were only slightly in favour of infliximab (€6.959/€3.625) relative to abatacept (€7.297/€3.909). Assuming extension of treatment under real life conditions the cost per month in remission/LDAS turned substantially in favour of abatacept (€5.321/€2.819), as compared to infliximab (€7.189/€3.916). The higher initiation cost for abatacept to achieve remission/LDAS would be offset after a total 14.6 and 16.1 months of treatment, respectively, if treatment extended beyond 6 months under real-life conditions. These results proved to be robust when it was assumed that the (i) sharing of vials across patients completely averted infliximab wastage, (ii) AE risks were similar and (iii) onset of response was slower for abatacept., Conclusions: Our findings suggest a lower cost-consequence for abatacept during real-life treatment.

This study aimed to evaluate the incidence of influenza-like illness (ILI), from October 2009 to May 2010, in a group of patients suffering from chronic inflammatory rheumatism and treated with biological therapies. At the end of 2009-2010 influenza season, 159 patients under biological therapies answered to a questionnaire distributed 8 months before and were deeply interviewed. The group included 69 men and 90 women (mean age 47.6); forty-nine suffering from rheumatoid arthritis, 61 with psoriatic arthritis, 32 with ankylosing spondylitis and 17 with other spondyloarthritis; 146 patients were treated with anti-TNF-α, 7 with rituximab and 6 with abatacept; 128 patients assumed DMARDs and 72 patients assumed low dose of steroids. A case of ILI was identified by anamnestic findings and according to the case definitions commonly used in Europe. Seventeen percent of the considered population reported at least one episode of ILI during the monitoring period; none of the patients during the acute influenza attack suffered particularly severe symptoms and no one was hospitalized due to complications. Despite the diversity among the considered subgroups, the statistical analysis did not show any significant difference when incidence of ILI was considered for different disease, different biological agent and different association therapy. None of the examined variables resulted statistically significant concerning the relative risk evaluation. The incidence of ILI into a cohort of 159 patients treated with biological agents during the influenza season 2009-2010 resulted higher than the value reported in a wide sample of Italian population in the same period. However, the pandemic impact was not heavy among the studied patients, considering that no important complications or hospitalizations have been reported.

Objectives: The objective of this Budget Impact Analysis is to evaluate the financial implications of a rituximab-based sequencing strategy in the treatment of rheumatoid arthritis in the perspective of the Italian National Health Service., Methods: Yearly patients who were eligible for a second-line biological DMARD in Italy were entered into a 5-year model. A Markov chain reproduced the course of this cohort under a number of alternative strategies, including anti-TNF-α cycling and rituximab or abatacept as second and third line agents. The dynamic of the simulation was given by first biological drug failure data, mortality rates, and survival-on-treatment data from published literature. Drug acquisition, administration and monitoring costs were assessed., Results: Italian patients refractory to a first anti-TNF-α therapy resulted to be about 650 per year, giving a cumulative number of treated patients in five years of 3,240. The anti-TNF-α cycling had a total direct cost which rose from €8.2 million in the first year to €33.8 million in the fifth. The cost per patient of rituximab was lower than the average cost of the anti-TNF-α therapies; the annual difference was around € 4,300. The savings gained from lower individual costs with rituximab were partially offset by the increasing number of patients receiving active medication, resulting in a substantial cost equivalence between third line rituximab and anti-TNF-α cycling scenarios; rituximab, as a second line therapy, produced a savings in total costs of -31.8%. Strategies including abatacept shared the same dynamics, but with higher costs., Conclusions: The introduction of rituximab in clinical practice could allow an increase in the number of patients receiving an active rheumatoid arthritis treatment without inflating therapy costs.

Background: In Caucasians, a small number of Type 1 diabetic patients do not show evidence of humoral islet autoimmunity at disease onset, at least with common screening procedures. In African- and Hispanic-American diabetic children at time of diagnosis, many show no evidence of autoimmunity but have an atypical clinical form of the disease. According to the recent American Diabetes Association classification, this subgroup of autoantibody negative patients is referred to as Type 1b diabetic subjects. In the present study, a homogeneous Caucasian Type 1 diabetic clinic-based cohort has been evaluated at diagnosis using a large panel of diabetes-related antibodies and then characterized for various genetic features in order to identify newly diagnosed Type 1 diabetics who are potentially autoantibody negative, i.e. possibly referrable to as idiopathic Type 1b diabetes., Methods: Newly diagnosed Type 1 diabetic patients of Italian origin (n=141, mean age 12.0+/-7.6 years) were tested for anti-islet cell, anti-insulin, anti-65 kDa isoform of glutamic acid decarboxylase and anti-amino acid residues 256-979 of the tyrosine-phosphatase IA-2 molecule autoantibodies (Step 1). Only those patients found to be autoantibody negative were tested for anti-disialo-ganglioside GD3, anti-thyroid peroxidase, anti-thyroglobulin, anti-21-OH hydroxylase, anti-gastric parietal cell and anti-transglutaminase antibodies (Step 2). Sera negative for the presence of these six autoantibodies as well were characterized in terms of HLA DRB1, DQB1 and CTLA-4., Results: Six out of 141 subjects (3.5%) were autoantibody negative in the first step of the study and five out of six in the second. These five autoantibody negative patients underwent genetic analysis. Three of them had at least one Type 1 diabetes-related high risk HLA haplotype (3/141, 2.1%) while the remaining two cases showed neutral (DR5-DQB1*0301/DR5-DQB1*0301) or strongly protective (DR2-DQB1*0602/DR2-DQB1*0602) HLA genotypes, respectively (2/141, 1. 4%)., Conclusions: Clinically defined Type 1 diabetic patients with no sign of autoimmunity do exist in a Caucasian population. These patients (2 out of 141) that cannot be classified as Type 1a diabetic patients lack clinical characteristics of Type 1b diabetes and have to be reconsidered for a more appropriate ADA classification. These data suggest the need of further large population-based studies to understand if Type 1b diabetes really occurs in a Caucasian population. The patient with a strongly protective HLA genotype is particularly interesting considering that among Caucasians only a few sporadic cases with Type 1 diabetes and DQB1*0602, have been reported, none of whom was homozygous at DQB1 locus., (Copyright 2000 John Wiley & Sons, Ltd.)

Objective: To determine whether 7 candidate genes, including tumor necrosis factor receptor II, bcl-2, CTLA-4, interleukin-10 (IL-10), CD19, Fcy receptor type IIA (CD32), and IL-1 receptor antagonist, may contribute to susceptibility to systemic lupus erythematosus (SLE) in the Italian population., Methods: The association with SLE of intragenic markers for each candidate gene, including either microsatellites or dimorphisms, was analyzed. Gene frequencies of these gene markers were compared for patients and ethnically matched controls. Significance was tested by chi-square test on 2 x 2 tables and by Monte Carlo simulation on 2 x N tables., Results: A significant increase was found in SLE patients (0.170 versus 0.095; chi2y = 4.11, P = 0.0425) in the frequency of the 140-basepair allele of the IL10.G microsatellite located in the promoter region of the IL-10 gene. This finding was confirmed in a second independent panel where, again, the frequency of the 140-bp allele was found to be significantly increased in SLE patients versus controls (0.176 versus 0.086; chi2y = 3.95, P = 0.0470). Considering the 2 panels together, the relative risk conferred by the presence of the 140-bp allele was 1.78 (95% confidence interval 1.19-2.66). Conversely, no significant association was detected for the remaining 6 candidate genes, even when the patients were stratified according to the presence of different clinical and immunologic features according to the presence of the associated HLA-DR or IL-10 alleles., Conclusion: Of the 7 candidate genes tested, only IL-10 was significantly associated with SLE in Italian patients. This genetic marker represents, apart from HLA, the only genetic susceptibility factor for SLE found so far in the Italian population.

Coeliac disease (CD) is a multifactorial disease for which there is an intensive search for genetic risk factors. Some authors found an association between the CTLA-4 region and CD. In the present work, we investigate the possible implication of the CTLA-4 region as a genetic risk factor for CD, through two statistical approaches: the maximum likelihood score (MLS) test in a large Italian sample of affected sib-pairs using polymorphic genetic markers on chromosome 2, and the transmission disequilibrium test (TDT) in continental Italian and Tunisian families using the CTLA-4 exon 1 49 A/G polymorphism. None of these approaches provides evidence for linkage or association between the CTLA-4 region and CD. This might result from a difference in the CTLA-4 region from population to population, either in its involvement as a risk factor or in the strength of linkage disequilibrium.