Belatacept 250mg powder for solution for infusion vials

Background The novel immunosuppressant belatacept demonstrates a unique mechanism of action that significantly improves renal function and reduces metabolic complications. However, systematic evidence comparing the risk of post-transplant diabetes mellitus (PTDM) and overall safety profiles between belatacept-based regimens and calcineurin inhibitor (CNI)-based protocols remains limited. This meta-analysis aims to synthesize high-quality evidence to determine the comparative efficacy of these two regimens in PTDM prevention and safety outcomes, thereby providing robust guidance for clinical decision-making. Methods We systematically searched PubMed, Cochrane Library, CNKI, and EMBASE for studies published until November 30, 2024, comparing belatacept versus calcineurin inhibitors (CNIs) regarding PTDM risk in kidney transplant recipients. The primary outcome was PTDM incidence. Following data extraction and quality assessment, we performed pairwise meta-analyses to compare PTDM risk between belatacept (either less intensive(LI) or more intensive (MI) regimen) and CNIs. Bayesian network meta-analysis (WinBUGS 1.4.3) was then conducted for indirect comparison between belatacept LI and MI regimens. Results The initial search yielded 3,206 records. After deduplication, title/abstract screening, and full-text evaluation, 6 studies involving 1,737 kidney transplant recipients were included in the final analysis. Compared with CNIs, belatacept demonstrated significant reductions in PTDM risk for both the LI (RR = 0.65, 95% CI 0.52-0.81, p<0.001; I²=30%) and MI (RR = 0.65, 95% CI 0.52-0.81, p<0.001; I²=30%) regimens. Bayesian network meta-analysis revealed no statistically significant difference between the LI and MI regimens. Conclusions This meta-analysis demonstrates that belatacept significantly reduces PTDM risk compared to CNIs, a finding consistent with previous studies. Notably, both LI and MI dosing regimens showed protective effects, suggesting that even low-intensity belatacept therapy could serve as a viable alternative to CNIs, particularly for patients requiring reduced immunosuppressive toxicity. Systematic review registration https://inplasy.com/, identifier INPLASY202540041.

Abstract licence: CC BY

Vascularized composite allotransplantation (VCA) enables functional reconstruction for patients with extensive tissue defects, but has obstacles such as immune rejection, lifelong immunosuppression, and systems-level barriers that limit widespread adoption. VCA has rapidly evolved through novel surgical, immunologic, and bioengineering technologies. This systematic review synthesizes the current landscape of emerging VCA technologies, identifies literature gaps, and emphasizes opportunities for future research. We conducted a systematic literature review of PubMed and Embase with supplemental manual reference review. English-language experimental studies reporting novel VCA technologies and innovations published after 2004 were included. Case reports, reviews, studies without technological innovation, and non-English publications were excluded. Seventy-two studies fit the inclusion criteria. Novel immunomodulation strategies including belatacept, phototherapy, siRNA therapeutics, and tolerance induction via regulatory T-cells show potential to reduce systemic immunosuppression, while mesenchymal stem cell approaches may increase graft tolerance. On another front, advanced surgical techniques with real-time monitoring and nerve regeneration protocols are looking to promote functional recovery. Digital innovations like 3D modeling and virtual surgical planning allow for patient-specific preoperative planning and intra-operative assistance. In parallel, machine perfusion and cryopreservation extend tolerable ischemia times and may also enable early rejection detection. Similarly, biomarkers and imaging provide early and noninvasive rejection prediction. On a bigger scale, patient selection incorporating evidence-backed psychosocial factors and communication training work to address systems-level barriers to expand access. Ongoing research to translate these innovations into clinical practice will be important in realizing the potential of VCA.

Abstract licence: CC BY

BackgroundAbatacept (ABA) and belatacept (BEL) are immunomodulatory fusion proteins in which the extracellular domain of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is linked to the Fc fragment of human IgG1. Functionally, they bind to cell surface antigens CD80 and CD86 on antigen-presenting cells, thereby preventing CD28-mediated costimulatory signaling. This systematic review aims to evaluate the clinical efficacy of ABA and BEL in immune-mediated diseases, focusing on indications currently not approved by the United States Food and Drug Administration (FDA) or the European Medicines Agency (EMA).MethodsWe searched PubMed and Web of Science for reports describing clinical efficacy of ABA or BEL in at least one patient with immune-mediated conditions outside FDA/EMA-approved indications. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist guided our data reporting.ResultsOf 5333 articles initially extracted, 2778 unique records were screened after de-duplication, and 96 matched our criteria and were included in this study. ABA was beneficial in patients diagnosed with Sjögren's syndrome (particularly secondary forms); autoimmunity in association with immunodeficiency; early, inflammatory and normal-like subtypes of systemic sclerosis; scleroderma; arthritis in systemic lupus erythematosus; inflammatory myopathies (polymyositis, immune-mediated necrotizing myositis, and antisynthetase syndrome); and giant-cell arteritis. Lower-level evidence studies reported positive results using ABA to treat granulomatosis with polyangiitis; relapsing polychondritis; sarcoidosis; and inflammatory eye diseases. Results of several studies highlighted the positive impact of ABA on arthritis in patients taking this drug for other indications. Likewise, several autoimmune diseases responded effectively to ABA when used to treat concomitant rheumatoid arthritis. Positive serological responses suggesting downstream modulation of B cell activation were reported in several randomized controlled trials. BEL was used after kidney transplantation in patients with proteinuric kidney disease or lupus nephritis, and in a few non-transplanted CTLA-4 haploinsufficiency carriers for immunodeficiency-associated autoimmunity.ConclusionsOur results provide a comprehensive summary of the efficacy of ABA and BEL across a broad spectrum of autoimmune diseases.

Abstract licence: CC BY-NC