Lack of efficacy of abatacept in axial spondylarthropathies refractory to tumor-necrosis-factor inhibition

Lekpa, Fernando Kemta; Farrenq, Valérie; Canouï‐Poitrine, Florence; Paul, Muriel; Chevalier, Xavier; Bruckert, R.; Bastuji‐Garin, Sylvie; Claudepierre, Pascal

doi:10.1016/j.jbspin.2011.02.018

Cited by 38 publications

(22 citation statements)

References 14 publications

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“…Therefore, the long term benefits of belatacept in renal transplant may outweight the drawbacks (Ford et al, 2014; Vincenti et al, 2010). Abatacept therapy slows c-peptide decline and lowers HgbA1C1 levels in patients with recent-inset type 1 diabetes (Lekpa et al, 2012; Orban et al, 2014; Orban et al, 2011). CTLA4Ig also showed clinical efficacy in a phase I trial in patients with psoriasis vulgaris (Abrams et al, 1999).…”

Section: Costimulatory Therapeutics: Manipulation Of Costimulatory Pamentioning

confidence: 99%

CD28 Costimulation: From Mechanism to Therapy

et al. 2016

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Summary Ligation of the CD28 receptor on T cells provides a critical second signal alongside T cell receptor (TCR) ligation for naive T cell activation. Here we discuss the expression, structure, and biochemistry of CD28 and its ligands. CD28 signals play a key role in many T cell processes including cytoskeletal remodeling, production of cytokines, survival, and differentiation. CD28 ligation leads to unique epigenetic, transcriptional, and post-translational changes in T cells that cannot be recapitulated by TCR ligation alone. We discuss the function of CD28 and its ligands in both effector and regulatory T cells. CD28 is critical for regulatory T cell survival and the maintenance of immune homeostasis. We outline the roles that CD28 and its family members play in human disease and we review the clinical efficacy of drugs that block CD28 ligands. Despite the centrality of CD28 and its family members and ligands to immune function, many aspects of CD28 biology remain unclear. Translation of a basic understanding of CD28 function into immunomodulatory therapeutics has been uneven with both successes and failures. Such real-world results may stem from multiple factors including complex receptor-ligand interactions among CD28 family members, differences between the mouse and human CD28 families, and cell-type specific roles of CD28 family members.

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Section: Costimulatory Therapeutics: Manipulation Of Costimulatory Pamentioning

confidence: 99%

CD28 Costimulation: From Mechanism to Therapy

et al. 2016

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“…41 This lack of efficacy of abatacept in axSpA has since been confirmed in another small trial. 42 Monoclonal antibodies directed against the IL6 receptor, which include tocilizumab (quite effective in the treatment of RA), seem to lack efficacy in patients with AS, in contrast to some earlier positive case reports. Detailed results of two placebocontrolled trials of these antibodies in patients with active AS are expected in the near future.…”

Section: Immunogenicity Efficacy and Switchingmentioning

confidence: 93%

Developments in therapies for spondyloarthritis

Sieper

2012

Nat Rev Rheumatol

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First-line therapy for spondyloarthritis (SpA) has not yet altered in the wake of new classification criteria; NSAIDs and physical therapy are recommended. Anti-TNF agents can be used when NSAIDs fail, but their efficacy has potentially been limited in previous trials by inclusion criteria requiring the presence of established, active disease. Now, not only patients with axial SpA (axSpA) with radiographic signs of sacroiliitis (that is, with ankylosing spondylitis), but also patients in whom structural damage is not-yet-visible radiographically (non-radiographic axSpA) can be included in trials of therapy for axSpA. TNF blockers, it seems already, are at least similarly effective in patients with non-radiographic axSpA as in those with established AS. Short symptom duration and a positive C-reactive protein test at baseline are currently the best predictors for a good response to TNF-blocking agents. Biologic agents besides anti-TNF therapies have so far failed in the treatment of axSpA. New bone formation seems currently to be best prevented by NSAIDs, not by TNF blockers. Whether earlier effective treatment of bony inflammation with anti-TNF therapy will be able to prevent ossification at a later stage has yet to be determined. New classification criteria for peripheral SpA will also allow treatment trials to be conducted more systematically than has previously been possible in this subgroup of patients.

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“…Recommendation 26. There is no evidence for the use of other biologics in SpA, including abatacept (ABA), tocilizumab (TCZ), and anakinra 137,138,139,140,141,142,143,144,145,146,147,148 . Interest ingly, a 6-month, randomized, double-blind, placebo-controlled study of ABA in PsA suggested that it may be effective at a dose of 10 mg/kg, potentially indicating a differential effect in peripheral versus axial disease 137 .…”

Section: Other Biologic Agentsmentioning

confidence: 99%