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Scleroderma
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Abatacept is currently FDA approved for the treatment of moderate to severe rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and active psoriatic arthritis. In mouse models of SSc, abatacept has also been shown to prevent experimental dermal fibrosis and also induces regression of established inflammation-driven fibrosis (97). In preclinical mouse models of chronic graft-versus-host disease and SSc, abatacept significantly reduced T cell proliferation and M1/M2 macrophage infiltration and limited B cell infiltrates (98). Based on this preclinical data, it was not surprising to see the completion of the Abatacept Systemic SclErosis (ASSET) Trial, a phase 2 RCT evaluating the safety and efficacy of abatacept in patients with early diffuse SSc (99). Although the trial did not meet the primary outcome, which was defined as the change from baseline in mRSS at twelve months, the numerical change in the mRSS favored active therapy. The open-label data at eighteen months showed clinically meaningful improvements in the mRSS and FVC in both the abatacept treated and placebo groups, but slightly higher improvements in the mRSS (100). Overall, these studies, including the ASSET trial, highlighted the need for a larger phase 3 RCT in early diffuse SSc.
Drug Repurposing and Novel Antiviral Drugs for COVID-19 Management
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Shailendra Dwivedi, Aakanksha Rawat, Amit Ranjan, Ruchika Agrawal, Radhieka Misra, Sunil Kumar Gupta, Surekha Kishore, Sanjeev Misra
Abatacept is a selective T cell costimulatory immuno-modulator with an extracellular domain of human cytotoxic T cell-associated antigen 4 fused to a modified immunoglobulin. It prevents full activation of T cells, resulting in inhibition of the downstream inflammatory cascade. An epidemiological survey performed in a large tertiary hospital in Barcelona, Spain, indicated that abatacept-treated patients (42 patients from a cohort of 959 patients treated with biological and synthetic disease-modifying anti-rheumatic drugs [DMARDs]) exhibited the lowest frequency of COVID-19–compatible symptoms [45]. Similar data were also obtained from a hospital in Madrid, Spain, where it was noted that none of the 27 abatacept-treated patients (among 802 DMARD-treated patients) were admitted to hospital with COVID-19 symptoms [46].
Newer Agents in Systemic Treatment
Published in Vineet Relhan, Vijay Kumar Garg, Sneha Ghunawat, Khushbu Mahajan, Comprehensive Textbook on Vitiligo, 2020
Rachita Dhurat, Shilpi Agarwal
Abatacept is known to decrease T cell activity in rheumatoid arthritis and hence its role is being deciphered in psoriasis and vitiligo. It acts via CTLA4 pathway and is self-administered weekly 125 mg subcutaneously [55]. Few studies are underway for treatment of vitiligo via TNF-α inhibitors like infliximab, etanercept, and adalimumab [56]. Vitiligo patients have a defective WNT signaling pathway and hence WNT activation could play a role in treatment of vitiligo. Further large-scale studies and trials are needed to bring all these newer systemic agents in clinical practice.
Biologics and small molecules in the management of psoriatic arthritis: Reproduction related issues in female and male patients
Published in Expert Review of Clinical Pharmacology, 2021
Rebecca Fischer-Betz, Monika Østensen
Biologics that have a proven positive effect both on skin and musculoskeletal symptoms in psoriatic disease include the TNFi, IL-17 and IL-23 inhibitors. When deciding how to treat before or during pregnancy, TNFi are the first-line choice due to extensive pregnancy experience. They have not shown negative effects on male or female fertility. Several studies have shown that cessation of treatment with TNFi before pregnancy is associated with flares during pregnancy and the postpartum period. Disease control should therefore be maintained before conception as well as during and after pregnancy. According to international guidelines, they can be used before conception and throughout pregnancy and during lactation when indicated. TNFi with a low rate of transplacental passage should be preferred. Given the paucity of pregnancies with abatacept and ustekinumab exposure, a definitive conclusion cannot be made regarding their safety in pregnancy. However, by knowledge gained from other biologics, an administration until the second trimester could be considered in the absence of effective alternative therapies. Newer IL-17 inhibitors and IL-23p19 inhibitors lack human pregnancy data and should therefore be avoided since no statements can be made on their compatibility with pregnancy.
Swedish Society of Rheumatology 2018 guidelines for investigation, treatment, and follow-up of giant cell arteritis
Published in Scandinavian Journal of Rheumatology, 2019
C Turesson, O Börjesson, K Larsson, AJ Mohammad, A Knight
Abatacept is a humanized fusion protein that modifies co-stimulation in antigen presentation, thereby inhibiting T-cell activity. Several experimental studies indicate that activated T cells play a role in the pathogenesis of GCA, and activated T cells have been found in arterial biopsies from GCA patients (31). Abatacept has been tested in a phase II study with 49 patients with either new or relapsing GCA, where it was given in combination with glucocorticoids (32). Relapse-free survival was significantly better and relapse frequency was lower in the abatacept group compared to the glucocorticoid-only group. The percentage of serious side effects was the same in both groups (32). To sum up, the addition of abatacept to glucocorticoid treatment results in a lower risk for relapse than with glucocorticoids alone (low quality of evidence). Treatment with abatacept may be considered when there are serious side effects from tocilizumab or when there is a contraindication for tocilizumab.
Long-term deterioration of interstitial lung disease in patients with rheumatoid arthritis treated with abatacept
Published in Modern Rheumatology, 2019
Takeshi Mochizuki, Katsunori Ikari, Koichiro Yano, Motoaki Sato, Ken Okazaki
This retrospective clinical study investigated the clinical course and background variables of patients with RA that fulfilled the American College of Rheumatology (ACR) classification criteria (1987) or/and the ACR/European League against Rheumatism (EULAR) criteria [16,17]. Patients were excluded if they discontinued abatacept due to inadequate efficacy, infections, or serious diseases such as malignancy within 1 year. A total of 131 consecutive patients with RA who had been treated with abatacept for more than 1 year were enrolled in this study. Eighty-five patients received intravenous abatacept and 46 patients received subcutaneous abatacept. Intravenous abatacept was administered as a 30-min infusion on day 0 (first infusion) and at 2, 4, and every 4 weeks thereafter. Patients weighing <60, 60–100, or >100 kg received 500, 750, or 1000 mg of abatacept, respectively. Subcutaneous abatacept was administered at 125 mg once weekly.