Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study

Visvanathan, Sudha; Daniluk, Stefan; Ptaszynski, R.; Müller‐Ladner, Ulf; Ramanujam, Meera; Rosenstock, Bernd; Eleftheraki, Anastasia G; Vinisko, Richard; Petrikova, A.; Kellner, Herbert; Dokoupilová, Eva; Kwiatkowska, Brygida; Alten, Rieke; Schwabe, Christian; Baum, Patrick; Joseph, David; Fine, Jay S.; Padula, Steven J.; Steffgen, Jürgen

doi:10.1136/annrheumdis-2018-214729

Cited by 45 publications

(35 citation statements)

References 31 publications

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“…However, the phase II RCTs with abatacept in patients with SLE arthritis did not meet the primary endpoints [67,68] and were stopped. CD40-CD40L blockade is currently being tested in patients with LN after a successful phase IIa RCT in patients with rheumatoid arthritis [69].…”

Section: Emerging Therapiesmentioning

confidence: 99%

Systemic Lupus Erythematosus (SLE) Therapy: The Old and the New

et al. 2020

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Despite recent improvements in the treatment of systemic lupus erythematosus (SLE), disease activity, comorbidities and drug toxicity significantly contribute to the risk of progressive irreversible damage accrual and increased mortality in patients with this chronic disease. Moreover, even lupus patients in remission often report residual symptoms, such as fatigue, which have a considerable impact on their health-related quality of life. In recent decades, SLE treatment has moved from the use of hydroxychloroquine, systemic glucocorticosteroids and conventional immunosuppressive drugs to biologic agents, of which belimumab is the first and only biologic agent approved for the treatment for SLE to date. Novel therapies targeting interferons, cytokines and their receptors, intracellular signals, plasma cells, T lymphocytes and co-stimulatory molecules are being evaluated. In the context of a holistic approach, growing evidence is emerging of the importance of correct lifestyle habits in the management of lupus manifestations and comorbidities. The aim of this paper is to provide an overview of current pharmacological and non-pharmacological treatment options and emerging therapies in SLE.

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Section: Emerging Therapiesmentioning

confidence: 99%

Systemic Lupus Erythematosus (SLE) Therapy: The Old and the New

et al. 2020

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“…CFZ533 is an anti-CD40 mAb with a modified Fc domain ( Ristov et al, 2018 ), and a phase I/II clinical trial for kidney transplantation showed efficacy. BI-655064, a humanized anti-CD40 mAb, is involved in an ongoing clinical trial to investigate the safety, efficacy, and therapeutic mechanism against autoimmune diseases ( Visvanathan et al, 2019 ).…”

Section: Immunomodulating Agents In Xenotransplantationmentioning

confidence: 99%

Corneal xenotransplantation: Where are we standing?

Yoon¹,

Choi²,

Kim

2021

Progress in Retinal and Eye Research

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The search for alternatives to allotransplants is driven by the shortage of corneal donors and is demanding because of the limitations of the alternatives. Indeed, current progress in genetically engineered (GE) pigs, the introduction of gene-editing technology by clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9, and advanced immunosuppressants have made xenotransplantation a possible option for a human trial. Porcine corneal xenotransplantation is considered applicable because the eye is regarded as an immune-privileged site. Furthermore, recent non-human primate studies have shown long-term survival of porcine xenotransplants in keratoplasty. Herein, corneal immune privilege is briefly introduced, and xenogeneic reactions are compared with allogeneic reactions in corneal transplantation. This review describes the current knowledge on special issues of xenotransplantation, xenogeneic rejection mechanisms, current immunosuppressive regimens of corneal xenotransplantation, preclinical efficacy and safety data of corneal xenotransplantation, and updates of the regulatory framework to conduct a clinical trial on corneal xenotransplantation. We also discuss barriers that might prevent xenotransplantation from becoming common practice, such as ethical dilemmas, public concerns on xenotransplantation, and the possible risk of xenozoonosis. Given that the legal definition of decellularized porcine cornea (DPC) lies somewhere between a medical device and a xenotransplant, the preclinical efficacy and clinical trial data using DPC are included. The review finally provides perspectives on the current standpoint of corneal xenotransplantation in the fields of regenerative medicine.

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“…BI-655064 demonstrated safety and was well tolerated in a cohort of healthy volunteers (92). In a doubleblind, randomized Phase 2a trial (NCT01751776), patients with RA received either weekly BI-655064 (120 mg) or placebo as add-on therapy to methotrexate (93). The primary endpoint of an ACR20 response at week 12 was seen in 68.2% in the active arm (n=44) compared to 45.5% in placebo (p=0.06).…”

Section: Targeting Cd40/cd40l In Ra Vib4920 (Medi4920) Is a Novel Cd4mentioning

confidence: 99%

Rationale for CD40 pathway blockade in autoimmune rheumatic disorders

Pucino

Gardner

Fisher

2020

The Lancet Rheumatology

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CD40 and CD40L (CD154) belong to the tumour necrosis factor receptor superfamily and are expressed by immune and non-immune cells. CD40L plays a central role in co-stimulation and regulation of the immune response via activation of CD40-expressing cells. Imbalance of the CD40/CD40L costimulatory pathway is reported in many autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SS) thus supporting its role in the breach of immune tolerance typical of these diseases. Targeting CD40/CD40L signalling may represent a novel therapeutic option for several autoimmune disorders. Key points: 1. CD40/CD40L signalling pathway regulates immune and non-immune cell responses 2. CD40/CD40L signalling is altered in autoimmune diseases such as SLE, RA, and SS 3. Early clinical trials programmes targeting CD40L were halted due to thrombotic adverse events 4. New therapeutic approaches targeting CD40 or using modified molecules against CD40L are currently being tested 5. Targeting CD40/CD40L signalling is a promising novel therapeutic strategy for reducing inflammation in autoimmune rheumatic disorders

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Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study

Cited by 45 publications

References 31 publications

Systemic Lupus Erythematosus (SLE) Therapy: The Old and the New

Systemic Lupus Erythematosus (SLE) Therapy: The Old and the New

Corneal xenotransplantation: Where are we standing?

Rationale for CD40 pathway blockade in autoimmune rheumatic disorders

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