T-cell Co-stimulation Modulator Research Articles

Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial

Individuals with serum antibodies to citrullinated protein antigens (ACPA), rheumatoid factor, and symptoms, such as inflammatory joint pain, are at high risk of developing rheumatoid arthritis. In the arthritis prevention in the pre-clinical phase of rheumatoid arthritis with abatacept (APIPPRA) trial, we aimed to evaluate the feasibility, efficacy, and acceptability of treating high risk individuals with the T-cell co-stimulation modulator abatacept. The APIPPRA study was a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial done in 28 hospital-based early arthritis clinics in the UK and three in the Netherlands. Participants (aged ≥18 years) at risk of rheumatoid arthritis positive for ACPA and rheumatoid factor with inflammatory joint pain were recruited. Exclusion criteria included previous episodes of clinical synovitis and previous use of corticosteroids or disease-modifying antirheumatic drugs. Participants were randomly assigned (1:1) using a computer-generated permuted block randomisation (block sizes of 2 and 4) stratified by sex, smoking, and country, to 125 mg abatacept subcutaneous injections weekly or placebo for 12 months, and then followed up for 12 months. Masking was achieved by providing four kits (identical in appearance and packaging) with pre-filled syringes with coded labels of abatacept or placebo every 3 months. The primary endpoint was the time to development of clinical synovitis in three or more joints or rheumatoid arthritis according to American College of Rheumatology and European Alliance of Associations for Rheumatology 2010 criteria, whichever was met first. Synovitis was confirmed by ultrasonography. Follow-up was completed on Jan 13, 2021. All participants meeting the intention-to-treat principle were included in the analysis. This trial was registered with EudraCT (2013-003413-18). Between Dec 22, 2014, and Jan 14, 2019, 280 individuals were evaluated for eligibility and, of 213 participants, 110 were randomly assigned to abatacept and 103 to placebo. During the treatment period, seven (6%) of 110 participants in the abatacept group and 30 (29%) of 103 participants in the placebo group met the primary endpoint. At 24 months, 27 (25%) of 110 participants in the abatacept group had progressed to rheumatoid arthritis, compared with 38 (37%) of 103 in the placebo group. The estimated proportion of participants remaining arthritis-free at 12 months was 92·8% (SE 2·6) in the abatacept group and 69·2% (4·7) in the placebo group. Kaplan-Meier arthritis-free survival plots over 24 months favoured abatacept (log-rank test p=0·044). The difference in restricted mean survival time between groups was 53 days (95% CI 28-78; p<0·0001) at 12 months and 99 days (95% CI 38-161; p=0·0016) at 24 months in favour of abatacept. During treatment, abatacept was associated with improvements in pain scores, functional wellbeing, and quality-of-life measurements, as well as low scores of subclinical synovitis by ultrasonography, compared with placebo. However, the effects were not sustained at 24 months. Seven serious adverse events occurred in the abatacept group and 11 in the placebo group, including one death in each group deemed unrelated to treatment. Therapeutic intervention during the at-risk phase of rheumatoid arthritis is feasible, with acceptable safety profiles. T-cell co-stimulation modulation with abatacept for 12 months reduces progression to rheumatoid arthritis, with evidence of sustained efficacy beyond the treatment period, and with no new safety signals. Bristol Myers Squibb.

A Real-World Evidence Comparison of 1-Year Overall Survival and Relapse-Free Survival between Patients Treated with Abatacept in Combination with a Calcineurin Inhibitor and Methotrexate Versus Antithymocyte Globulin or Post-Transplant Cyclophosphamide Following Allogeneic Hematopoietic Cell Transplantation

Introduction: Matched sibling or matched unrelated donor (MUD) availability remains a clinical challenge for hematopoietic cell transplant (HCT) recipients. Though HCTs with a mismatched unrelated donor (MMUD) may be an option, graft-versus-host disease (GVHD)-related mortality risk is elevated with MMUD HCTs. Abatacept (ABA), a selective T-cell costimulation modulator, when administered with calcineurin inhibitor/methotrexate (CNI/MTX), improved survival outcomes in 7/8 MMUD and 8/8 MUD recipients (Watkins B, et al. J Clin Oncol 2021) compared with CNI/MTX prophylaxis alone and was approved in the United States for acute GVHD prophylaxis (US FDA 2021). Alternative prophylactics, such as antithymocyte globulin (ATG) + CNI/MTX or post-transplant cyclophosphamide (PT-Cy) + tacrolimus (Tac) + mycophenolate mofetil (MMF) also show promise for improving post-HCT survival outcomes (Walker I, et al. Lancet Haematol 2020; Shaw B, et al. J Clin Oncol 2021; Luznik L, et al. J Clin Oncol 2022). This real-world analysis compared survival outcomes in 7/8 MMUD and 8/8 MUD recipients treated with ABA + CNI/MTX versus ATG + CNI/MTX and versus PT-Cy + Tac + MMF from the Center for International Blood and Marrow Transplant Research (CIBMTR) database of all allogeneic HCTs performed in the United States. Methods: This retrospective cohort study included CIBMTR database allogenic HCT recipients treated with ABA + CNI/MTX, ATG + CNI/MTX, and PT-Cy + Tac + MMF (PT-Cy). Recipients were aged ≥ 6 years; weighed ≥ 20 kg; had a Karnofsky/Lansky performance score ≥ 80%; were diagnosed with leukemia, lymphoma, or myelodysplastic syndrome; and underwent first allogeneic HCT from a 7/8 MMUD or 8/8 MUD in the United States between 2011 and 2018. Overall survival (OS; time between HCT date and documented date of death) and relapse-free survival (RFS; time between HCT date and date of death or relapse, whichever occurred first) were evaluated over 1 year post-HCT. A weighted log-rank test was used to compare outcomes using inverse probability of treatment weighting (IPTW), based on propensity score calculation to control for treatment bias. Marginal hazard ratios (HRs) and 95% CIs were estimated by a weighted Cox proportional hazards model with treatment as a covariate. Results: The 7/8 MMUD cohort included 378 recipients: 54 ABA + CNI/MTX, 162 ATG + CNI/MTX, and 162 PT-Cy. The 8/8 MUD cohort included 781 recipients: 71 ABA + CNI/MTX, 355 ATG + CNI/MTX, and 355 PT-Cy. For 7/8 MMUD recipients, OS (95% CI) was significantly higher with ABA + CNI/MTX (87% [67-95%]) versus ATG + CNI/MTX (58% [49-66%]); P = 0.0026; HR (95% CI): 0.24 (0.10-0.55). The OS comparison between ABA + CNI/MTX versus PT-Cy was 86% (66-94%) and 79% (70-85%), respectively; P = 0.3376; HR (95% CI): 0.61 (0.25-1.51). In 8/8 MUD recipients, OS (95% CI) was significantly higher with ABA + CNI/MTX versus ATG + CNI/MTX (86% [72-93%] versus 70% [65-75%], respectively); P = 0.0209; HR (95% CI): 0.43 (0.21-0.88). The OS comparison for ABA + CNI/MTX versus PT-Cy was 84% (66-93%) versus 78% (73-82%), respectively; P = 0.3616; HR (95% CI): 0.69 (0.30-1.54). In 7/8 MMUD recipients, the ABA + CNI/MTX subgroup had significantly higher RFS versus ATG + CNI/MTX (81% [60-92%] versus 48% [39-56%], respectively); P = 0.0015; HR (95% CI): 0.27 (0.13-0.55). The RFS comparison between ABA + CNI/MTX versus PT-Cy was 75% (56-87%) versus 62% (52-70%), respectively; P = 0.1636; HR (95% CI): 0.60 (0.26-1.39). For 8/8 MUD recipients, Figure 1 shows ABA + CNI/MTX had significantly higher RFS versus ATG + CNI/MTX (82% [69-90%] versus 61% [55-66%], respectively); P = 0.0032; HR (95% CI): 0.39 (0.21-0.73). Figure 2 shows the RFS comparison between ABA + CNI/MTX and PT-Cy (79% [61-90%] versus 65% [60-70%], respectively); P = 0.0944; HR (95% CI): 0.54 (0.26-1.11). Conclusions: ABA + CNI/MTX significantly improved OS and RFS over 1-year post-HCT compared with ATG + CNI/MTX prophylaxis. There was a trend toward improved OS and RFS 1-year post-HCT on ABA + CNI/MTX compared with PT-Cy, although this did not reach statistical significance. OS and RFS in 7/8 MMUD recipients receiving ABA + CNI/MTX was similar to those in 8/8 MUD recipients, suggesting that this treatment improved the risk/benefit ratio for MMUD HCTs. Study support: This study was sponsored by Bristol Myers Squibb. Medical writing: Efrah Yousuf and Ryan Miller (Caudex), funded by Bristol Myers Squibb. We acknowledge Brian Gavin, PhD, for his contributions. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risk of hepatitis B virus reactivation following treatment with abatacept: A retrospective study of international pharmacovigilance databases

SummaryBackgroundAbatacept is a selective T-cell costimulation modulator approved for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, and psoriatic arthritis. Reports were recently published on hepatitis B virus reactivation (HBVr) in patients who were treated with abatacept. However, the literature is limited to case reports and series, and no study has investigated the relationship between HBVr and abatacept using extensive population-based databases.MethodsUsing the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database, we collected all cases of HBVr between Jan 1, 2006 and June 30, 2021, for abatacept and other drugs. Disproportionality was analysed using the reporting odds ratio (ROR), which was considered significant when the lower limit of the 95% CI was >1. We also conducted a confirmatory analysis in the European pharmacovigilance database, EudraVigilance.FindingsDuring the study period, 77,669 adverse cases were reported for abatacept use. There were 2889 reports of HBVr with any drug during this period, of which 55 were reported with abatacept. The ROR for HBVr with abatacept was significantly elevated at 4·80 (95% CI 3·68–6·27). All 55 cases of HBVr with abatacept were reported as serious adverse events. Of them, six individuals were hospitalised and four died. Among 832 reports of HBVr with any drug in EudraVigilance, 43 were reported with abatacept; the ROR was 8·99 (95% CI 6·61–12·23).InterpretationWe identified a positive signal between abatacept exposure and HBVr. Future prospective studies should further confirm the relationship and provide evidence to develop strategies involving pre-treatment screening, monitoring, and utilisation of antiviral prophylaxis when using abatacept in patients with rheumatic diseases.FundingThis work was supported by the Fundamental Research Funds for Central Universities (xjh012019063).

Model‐Based Selection and Recommendation for Subcutaneous Abatacept Dose in Patients With Polyarticular Juvenile Idiopathic Arthritis

The selective T‐cell costimulation modulator abatacept is approved for treatment of adult rheumatoid arthritis (RA) and polyarticular juvenile idiopathic arthritis (pJIA; 6‐17 years [intravenous] and 2‐17 years [subcutaneous]). An extrapolation approach was taken to determine subcutaneous weight‐tiered doses of abatacept to evaluate in patients with pJIA. Population pharmacokinetic (PPK) and exposure‐response (E‐R) analyses were conducted to determine whether the weight‐tiered subcutaneous regimen provides near‐maximal efficacy and is therapeutically comparable to the intravenous regimen in patients with pJIA aged 2‐17 years. Combined study data from intravenous or subcutaneous abatacept were used to assess clinically relevant exposure outcomes. The PPK model was developed with data from 13 phase 2/3 studies in RA and pJIA; the E‐R model for the American College of Rheumatology pediatric scores (JIA‐ACR 30/50/70/100 responses) in month 4 was developed with data from 2 phase 3 pJIA studies. Predefined covariates were investigated in both analyses. PPK model‐predicted exposures were steady‐state peak, trough (Cminss), and time‐averaged concentrations. Abatacept PK was characterized by a linear 2‐compartment model (zero‐order intravenous infusion, first‐order subcutaneous absorption, first‐order elimination); body weight was the only clinically relevant covariate. Cminss was the best exposure predictor for the JIA‐ACR response: log odds for response increased in proportion to log‐transformed Cminss; JIA‐ACR30 approached a plateau when Cminss ≥ 10 μg/mL. The PPK and E‐R analyses demonstrated that the weight‐tiered subcutaneous and intravenous abatacept dosing regimens provide near‐maximal efficacy and are clinically comparable across children with pJIA who are > 2 years old.

Trial of Upadacitinib or Abatacept in Rheumatoid Arthritis

BackgroundUpadacitinib is an oral selective Janus kinase inhibitor to treat rheumatoid arthritis. The efficacy and safety of upadacitinib as compared with abatacept, a T-cell costimulation modulator, in patients with rheumatoid arthritis refractory to biologic disease-modifying antirheumatic drugs (DMARDs) are unclear.MethodsIn this 24-week, phase 3, double-blind, controlled trial, we randomly assigned patients in a 1:1 ratio to receive oral upadacitinib (15 mg once daily) or intravenous abatacept, each in combination with stable synthetic DMARDs. The primary end point was the change from baseline in the composite Disease Activity Score for 28 joints based on the C-reactive protein level (DAS28-CRP; range, 0 to 9.4, with higher scores indicating more disease activity) at week 12, assessed for noninferiority. Key secondary end points at week 12 were the superiority of upadacitinib over abatacept in the change from baseline in the DAS28-CRP and the percentage of patients having clinical remission according to a DAS28-CRP of less than 2.6.ResultsA total of 303 patients received upadacitinib, and 309 patients received abatacept. From baseline DAS28-CRP values of 5.70 in the upadacitinib group and 5.88 in the abatacept group, the mean change at week 12 was −2.52 and −2.00, respectively (difference, −0.52 points; 95% confidence interval [CI], −0.69 to −0.35; P<0.001 for noninferiority; P<0.001 for superiority). The percentage of patients having remission was 30.0% with upadacitinib and 13.3% with abatacept (difference, 16.8 percentage points; 95% CI, 10.4 to 23.2; P<0.001 for superiority). During the treatment period, one death, one nonfatal stroke, and two venous thromboembolic events occurred in the upadacitinib group, and more patients in the upadacitinib group than in the abatacept group had elevated hepatic aminotransferase levels.ConclusionsIn patients with rheumatoid arthritis refractory to biologic DMARDs, upadacitinib was superior to abatacept in the change from baseline in the DAS28-CRP and the achievement of remission at week 12 but was associated with more serious adverse events. Longer and larger trials are required in order to determine the effect and safety of upadacitinib in patients with rheumatoid arthritis. (Funded by AbbVie; SELECT-CHOICE Clinicaltrials.gov number, NCT03086343.)

OP0238 RISK OF HERPES ZOSTER IN PATIENTS WITH RHEUMATOID ARTHRITIS UNDER BIOLOGICAL, TARGETED SYNTHETIC, AND CONVENTIONAL SYNTHETIC DMARD TREATMENT

Background:The risk of herpes zoster (HZ) is higher in patients with rheumatoid arthritis (RA) than in the general population. This risk is further increased with biologic disease-modifying anti-rheumatic drugs (bDMARDs) such as tumour necrosis factor inhibitors (TNFi) and targeted synthetic (ts)DMARDs such as Janus kinase inhibitors (JAKi) compared to patients taking conventional synthetic (cs)DMARDs such as methotrexate (MTX).Objectives:To compare incidence rates of HZ in RA patients under treatment with bDMARDs, tsDMARDs and csDMARDs with different modes of action and to find potential risk factors.Methods:Data of patients enrolled in the German biologics register RABBIT from 2007 onwards with the start of a bDMARD, tsDMARD or a change in csDMARD treatment were analysed. Patients were included when at least one follow-up documentation was available. All HZ events reported until 30 April 2019 were identified and assigned to treatments administered within the 3 month period prior to the HZ event. Crude incidence rates (IR) of HZ were calculated per 1,000 patient years (py). Cox regression was applied to investigate risk factors for the occurrence of HZ with and without inverse probability weights (IPW) to adjust for confounding by indication.Results:Data of 12,470 patients (53,218 py of observation) were included in the analysis. A total of 452 HZ cases in 433 patients were reported, of which 52 events were serious. The crude IRs per 1,000 py are illustrated by Figure. Adjusted for age, sex, and glucocorticoid use, a significantly increased risk was observed for treatment with monoclonal TNF antibodies (hazard ratio [HR], 1.55 [95% CI, 1.21-2.00]), B-cell targeted therapies (HR, 1.45 [95% CI, 1.07-1.97]), and tsDMARDs (HR, 3.55 [95% CI, 2.33-5.41]). Treatment with soluble TNF receptors, T-cell co-stimulation modulator, and IL-6 inhibitors were not significantly associated (Table). Adjustment with IPW amplified the effect and treatment with T-cell co-stimulation modulator and IL-6 inhibitors were also significantly associated with a higher risk compared to csDMARD treatment (Table).Conclusion:This is the first analysis in a European prospective cohort study comparing the incidence rates and risk of HZ in RA patients under treatment with six different modes of action within one cohort to csDMARD treatment. We found a significant association between HZ and treatment with JAKi. Our results also confirm a higher risk for monoclonal TNF antibodies and show a similar result for the T-cell co-stimulation modulator and B-cell targeted therapies. This study clearly supports systematic HZ vaccination of RA patients.Table.Risk of herpes zoster: Results of adjusted regression analyses with and without inverse probability weightsMultivariate Analysiswithout IPWMultivariate Analysiswith IPWAdjusted HR (95% CI)P ValueAdjusted HR (95% CI)P ValueFemale sex1.42 (1.12-1.82)0.00421.21 (0.96-1.53)0.1095Age per 10 years1.23 (1.13-1.33)&lt;.00011.31 (1.2-1.43)&lt;.0001Glucocorticoids, 5-10 vs 0 mg/d1.16 (0.95-1.41)0.15771.23 (1-1.52)0.0501Glucocorticoids, &gt;10 vs 0 mg/d1.58 (1.02-2.46)0.04171.92 (1.27-2.92)0.0022csDMARD treatmentReferenceReferenceMonoclonal TNFi antibodies1.55 (1.20-2.00)0.00091.63 (1.25-2.12)0.0003Soluble TNF receptors1.32 (0.98-1.77)0.06831.34 (0.98-1.83)0.0631T-cell co-stimulation modulator1.41 (0.97-2.05)0.07461.69 (1.17-2.45)0.0048B-cell targeted therapies1.45 (1.07-1.97)0.01561.66 (1.19-2.3)0.0026IL-6 inhibitors1.31 (0.97-1.77)0.07371.55 (1.15-2.09)0.0045JAK inhibitors3.55 (2.33-5.41)&lt;.00015.01 (3.45-7.28)&lt;.0001Acknowledgments:RABBIT is supported by a joint, unconditional grant from AbbVie, Amgen, BMS, Fresenius Kabi, Hexal, Lilly, MSD, Mylan, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis and UCBDisclosure of Interests:Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Imke Redeker: None declared, Jörn Kekow Speakers bureau: BMS, MSD, Pfizer, Roche, Gerd Rüdiger Burmester Consultant of: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Speakers bureau: AbbVie Inc, Eli Lilly, Gilead, Janssen, Merck, Roche, Pfizer, and UCB Pharma, Juergen Braun Grant/research support from: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, Eli Lilly and Company, Medac, MSD (Schering Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi- Aventis, and UCB Pharma, Consultant of: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Speakers bureau: Abbvie (Abbott), Amgen, BMS, Boehringer, Celgene, Celltrion, Centocor, Chugai, EBEWE Pharma, Eli Lilly and Company, Medac, MSD (Schering-Plough), Mundipharma, Novartis, Pfizer (Wyeth), Roche, Sanofi-Aventis, and UCB Pharma, Angela Zink Speakers bureau: AbbVie, Amgen, BMS, Gilead, Hexal, Janssen, Lilly, MSD, Pfizer, Roche, Sanofi Aventis, UCB

Abatacept: from a budget impact model to cost-effectiveness analysis - data from RCT and real life.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder that affects joints with swelling and progressive joint destruction. The pathology leads to a progressive disability with an impact on the quality of life of the patients. Strategies to reduce in-patient care costs could have a considerable impact on lowering the direct medical costs of RA in Italy. Abatacept, a selective T-cell costimulation modulator, is a valuable treatment option for patients with moderate-to-severe RA. A search using the keywords “cost-effectiveness analysis", "budget impact model", "abatacept", and "rheumatoid arthritis” was carried out on PubMed. Abatacept in the first- and second-treatment lines has been evaluated in our research. We evaluated patients with inadequate MTX response, inadequate anti-TNF agents response, switch studies and real-world data. Furthermore, in our research, we evaluated the main head-to-head studies published.

Abatacept in the treatment of psoriatic arthritis: biological and clinical profiles of the responders.

Abatacept (CTLA4Ig), a selective T-cell costimulation modulator, has been approved for the treatment of psoriatic arthritis patients with an inadequate response to conventional synthetic disease-modifying antirheumatic drugs, but not for those with uncontrolled skin lesions, nor with axial involvement. In this review, we will try to interpret such a differential efficacy of abatacept on the psoriatic arthritis clinical domains, on the basis of its differential effectiveness on the diverse T-cell subsets at different sites. Clinical and biological profiles of possible responders to abatacept will be provided.

Pulmonary arterial hypertension associated with abatacept treatment for rheumatoid arthritis: A case report

ABSTRACTAbatacept (Orencia®, Bristol-Myers Squibb Canada) is a selective T-cell co-stimulation modulator that has an emerging role in the treatment of rheumatoid arthritis (RA). We present a case of a patient with RA who developed severe pulmonary arterial hypertension (PAH) after exposure to abatacept therapy. To our knowledge, this is the first case describing a possible association between abatacept and the development of PAH. A causal link between abatacept and PAH is not clear, but ongoing monitoring by physicians prescribing abatacept is important to monitor for other instances of this potentially serious complication.RÉSUMÉL'abatacept (Orencia®, Bristol-Myers Squibb Canada) est un modulateur sélectif de la costimulation des cellules T qui a un rôle émergent dans le traitement de l'arthrite rhumatoïde. Nous présentons le cas d'un patient atteint d'arthrite rhumatoïde qui a commencé à souffrir d'hypertension artérielle pulmonaire grave après un traitement par abatacept. À notre connaissance, il s'agit du premier cas décrivant une association possible entre l'abatacept et la survenue de l'hypertension artérielle pulmonaire. Il n'existe pas de lien causal clair entre l'abatacept et l'hypertension artérielle pulmonaire, mais il est important que les médecins qui prescrivent de l'abatacept effectuent un suivi continu pour surveiller l'apparition d'autres cas présentant cette complication potentiellement grave.

Efficacy and safety of abatacept, a T-cell modulator, in a randomised, double-blind, placebo-controlled, phase III study in psoriatic arthritis

ObjectivesTo assess the efficacy and safety of abatacept, a selective T-cell costimulation modulator, in a phase III study in psoriatic arthritis (PsA).MethodsThis study randomised patients (1:1) with active PsA (~60%...

FRI0023 Is Positivity of Rheumatoid Factor and Anti-Cyclic Citrullinated Peptide Associated with the Response Rate of Infliximab, Tocilizumab, and Abatacept in Treatment of Rheumatoid Arthritis?

BackgroundRecent reports have shown that positivity for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) can influence the efficacy of rheumatoid arthritis (RA) treatment. Additionally, RF+ and ACPA+ statuses were...

A critical evaluation of the role of subcutaneous abatacept in the treatment of rheumatoid arthritis: patient considerations

There are now more therapeutic options for the treatment of rheumatoid arthritis (RA) than ever before, involving a range of mechanisms of action and different routes of administration. The T-cell costimulation modulator abatacept is the first biologic therapy for RA to be available in both subcutaneous (SC) and intravenous (IV) formulations. This review evaluates the utility of SC abatacept, with a particular focus on patient-reported outcomes, including physical function, pain, fatigue, and quality of life. Practical questions relating to the clinical use of SC abatacept are also addressed, including the relevance of abatacept’s mechanism of action; whether IV and SC abatacept are comparable; if patients can easily switch from IV to SC abatacept; whether an IV loading dose is needed; and if temporary treatment interruptions or lack of concomitant methotrexate can affect efficacy or safety. Topics that are of particular concern to patients when using SC biologics, such as injection-site reactions, are also discussed. Observational data from registries and meta-analyses of clinical studies suggest comparable clinical efficacy between biologic disease-modifying antirheumatic drugs; however, such analyses rarely focus on key determinants of patient quality of life such as pain, fatigue, and physical function. The head-to-head AMPLE study is one of the first studies powered to directly compare two biologics in patients with RA. Patient-reported outcomes from year 1 of the ongoing study are evaluated, demonstrating comparable improvements in physical function, pain, fatigue, Short Form-36 Health Survey, and Routine Assessment of Patient Index Data 3 scores between SC abatacept and SC adalimumab when administered with concomitant methotrexate. In summary, the data presented herein show that the SC formulation of abatacept provides a valuable addition to the range of available therapy options for patients with RA, capable of significantly improving key patient considerations such as pain, disability, loss of function, fatigue, and quality of life.

Mesangial immunoglobulin (Ig)A glomerulonephritis in a patient with rheumatoid arthritis treated with abatacept

We report observations of a 47-year-old seropositive woman with rheumatoid arthritis (RA) suffering from mesangial immunoglobulin (Ig)A glomerulonephritis (GN) after initiation of abatacept, a selective T-cell co-stimulation modulator cytotoxic T-lymphocyte antigen 4 (CTLA4)-Ig. She was initially treated by corticosteroids, followed by methotrexate associated with a TNF inhibitor (adalimumab then switched to etanercept), finally switched to abatacept monotherapy, after secondary failure of these two forms of TNF inhibitors. Due to a progressively increased hematuria and proteinuria after abatacept therapy initiation, a renal biopsy was performed highlighting GN with mesangial IgA deposits, with necrosis and extracapillary crescent formations. IgA GN as a possible adverse event to abatacept was considered. Abatacept was stopped and a treatment by corticosteroids was initiated. Proteinuria decreased a couple of months after abatacept interruption. The short term between abatacept induction and IgA GN onset, as well as GN improvement since abatacept discontinuation, lend weight to the argument that CTLA4-Ig may play a crucial role in IgA GN pathogenesis. The possibility of a drug postponed adverse event justifies a long-term renal surveillance in RA patients treated by abatacept.

AB0553 Switching from SC to IV abatacept: Pharmacokinetic simulations to support dose regimen

BackgroundAbatacept (ABA) is a selective T-cell co-stimulation modulator approved in the US for RA, available in both IV and SC formulations. There is a need to establish a safe and...

Trichinellosis Masquerading as a Soft-Tissue Mass: A Case Report.

Trichinellosis, also known as trichinosis and trichiniasis, is a rare infection caused by the ingestion of raw or undercooked meat containing viable encysted larvae of the parasitic roundworm Trichinella species1-3. Previously quite common, the Centers for Disease Control and Prevention currently report only a few trichinellosis cases annually in the United States2,4. The scarcity of present-day cases is largely attributed to increased federal legislation over the past several decades that led to many public health measures to educate people regarding techniques for safe food preparation2,4-6. Trichinellosis usually presents acutely with circumorbital edema, fever, myalgia, and abdominal discomfort. We report a case in a fifty-seven-year-old woman who presented atypically with a soft-tissue mass in the forearm. Clinical presentation, diagnosis, prevention, and treatment of this rare infection are discussed. The patient was informed that data concerning her case would be submitted for publication, and she provided consent. A fifty-seven-year-old woman presented to the orthopaedic oncology service for evaluation of a painless mass in the left forearm, which had been slowly enlarging over several years. The patient's rheumatoid arthritis had caused finger deformities and diffuse rheumatoid nodules. At the time of presentation, the rheumatoid arthritis was being treated with abatacept, a T-cell costimulation modulator, but in the past it had been treated with other disease-modifying antirheumatic drugs. Additionally, she had a twenty-year history of anterior interosseous nerve syndrome of the right forearm, and a one-year history of anterior interosseous nerve syndrome of the left forearm, although the cause of these bilateral syndromes was unknown. Physical examination demonstrated a firm, fixed, painless mass on the volar side of the left forearm, proximal to the wrist crease. The patient had an absence of flexor pollicus longus and flexor digitorium profundus function …

Abatacept for severe anti-TNF-alfa refractory JIA-associated uveitis: one year follow-up

Uveitis in JIA can be severe and immunosoppressive therapies may not be sufficient. Anti-TNF-alfa agents (Infliximab, Adalimumab) have been proposed. The percentage of success is different among series and no controlled trials have been published yet. Abatacept, a selective T-cell co-stimulation modulator, has been shown to be a valid alternative to anti-TNF-alfa agents in patients with refractory uveitis (Angels-Han S.2008; Zulian 2010).

Abatacept treatment for rheumatoid arthritis

Significant advances in our understanding of RA and its management have been made in the past decade, resulting in earlier intervention with biologic DMARDs, particularly in patients with evidence of aggressive, erosive disease. Here, one such biologic therapy, the T-cell co-stimulation modulator abatacept, is discussed, exploring clinical evidence published to date on its use in patients with very early arthritis/early RA who are MTX naïve, and in patients with established RA and an inadequate response to MTX or TNF antagonists. Data from relevant clinical trials are overviewed, discussing the clinical efficacy of abatacept in early disease, the clinical outcomes over long-term treatment in different patient populations and the effects of abatacept on structural damage. Findings from integrated safety analyses of abatacept clinical trial data, representing 10 366 patient-years of exposure are described, and clinically important safety events, including serious infections, malignancies and autoimmune events, are highlighted. It is concluded that abatacept represents an effective treatment option with an established safety profile across different patient populations, including patients with both early and erosive RA and those with established disease. Furthermore, efficacy data from studies in patients with early disease suggest that the risk–benefit profile of abatacept may be more favourable when introduced earlier in the treatment paradigm.

Do new biologics meet the unmet medical need in rheumatoid arthritis? Safety and efficacy of abatacept following B-cell depletion

Sir, anti TNF-α agents (aTNFs) are the most commonly prescribed biological agents in RA. More recently abatacept (ABA), a T-cell costimulation modulator, and rituximab (RTX), a monoclonal antibody directed against CD20, have become available. Observational studies suggest that switching to a new drug class may be more effective in uncontrolled RA than switching to a class of biologics to which the patient had unsuccessfully been exposed [1]. Information about the efficacy and safety of cycling strategies through third-line biologics is lacking. This study aimed to analyse the effectiveness and safety of switching patients to ABA as the third biological class after failure of aTNF plus RTX. The Swiss Clinical Quality Management (SCQM) programme for RA is a longitudinal population-based cohort, which has been approved by the local ethics committees of all participating centres [2]. For this analysis, we collected all the …

Immunologic rheumatic disorders

We provide the basics for clinicians who might be called on to consider the diagnosis of diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in their practice. We will emphasize clinical recognition and first-line laboratory testing. Only characteristics of the classic rheumatic inflammatory diseases (ie, RA, seronegative spondyloarthropathy, SLE, antiphospholipid syndrome, Sjögren syndrome, scleroderma, and polymyositis/dermatomyositis) will be covered. In the past decade, treatment for RA and seronegative spondyloarthropathy has substantially improved. Their treatment has been revolutionized by the use of methotrexate and, more recently, TNF inhibitors, T-cell costimulation modulators, and B-cell depletion. The goal of RA treatment today is to induce a complete remission as early as possible in the disease process, with the mantra being "elimination of synovitis equals elimination of joint destruction." The hope is that if the major mediators of Sjögren syndrome, SLE, or scleroderma can be identified and then blocked, as in the example of TNF inhibitors in patients with RA, more specific treatments will become available. Thus RA has become an excellent model of this evolving paradigm. Through the identification of major mediators in its pathogenesis, novel and highly efficacious therapeutic agents have been developed.

Therapeutic agents for patients with rheumatoid arthritis and an inadequate response to tumour necrosis factor-α antagonists

Background: Rheumatoid arthritis (RA) is a disabling autoimmune disease; unless adequately controlled, patients have a poor long-term prognosis. Tumour necrosis factor (TNF)-α antagonists have provided relief for many RA patients; however, despite their efficacy, some patients do not respond or fail to maintain initial response. In the UK, patients with an inadequate response to TNF-α antagonists have limited options, as the National Institute of Clinical Excellence (NICE) currently only recommend switching to an alternative TNF-α antagonists if discontinuation occurs due to safety during the first 6 months of treatment. The EU has approved three biological agents, rituximab, abatacept, and tocilizumab, for patients with RA with an inadequate response to TNF-α antagonists. Objective: This review examines the clinical experience with two therapies targeting key immune cells involved in RA – rituximab (lyses B-cells), and abatacept (T-cell co-stimulation modulator) – specifically focusing on patients with an inadequate response to TNF-α blockade. Methods: Phase II/III clinical trials and original studies were identified using Medline and Pubmed; articles assessing the efficacy and/or safety of rituximab or abatacept in patients with RA refractory to TNF-α blockade were reviewed. Conclusions: Clinical data for rituximab and abatacept demonstrate that both reduce disease activity in TNF-α antagonist inadequate responders, suggesting that agents with alternative mechanisms of action, such as those targeting key immune cells, may be useful in this patient population.