scholarly journals B cell depletion may be more effective than switching to an alternative anti–tumor necrosis factor agent in rheumatoid arthritis patients with inadequate response to anti–tumor necrosis factor agents

2007 ◽  
Vol 56 (5) ◽  
pp. 1417-1423 ◽  
Author(s):  
Axel Finckh ◽  
Adrian Ciurea ◽  
Laure Brulhart ◽  
Diego Kyburz ◽  
Burkhard Möller ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Cell Depletion ◽  
Inadequate Response ◽  
B Cell Depletion ◽  
Necrosis Factor

scholarly journals Antibodies That Block or Activate Mouse B Cell Activating Factor of the Tumor Necrosis Factor (TNF) Family (BAFF), Respectively, Induce B Cell Depletion or B Cell Hyperplasia

2016 ◽  
Vol 291 (38) ◽  
pp. 19826-19834 ◽  
Author(s):  
Christine Kowalczyk-Quintas ◽  
Sonia Schuepbach-Mallepell ◽  
Michele Vigolo ◽  
Laure Willen ◽  
Aubry Tardivel ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
B Cell ◽  
Tumor Necrosis ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Cell Hyperplasia ◽  
B Cell Activating Factor ◽  
Necrosis Factor

scholarly journals AB0138 A MOLECULAR SIGNATURE RESPONSE CLASSIFIER STRATIFIES SEROPOSITIVE RHEUMATOID ARTHRITIS PATIENTS BASED ON THEIR LIKELIHOOD OF INADEQUATE RESPONSE TO TNF INHIBITOR THERAPIES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1096.3-1097
Author(s):  
S. Cohen ◽  
V. Strand ◽  
E. Connolly-Strong ◽  
J. Withers ◽  
L. Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Therapy ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Molecular Signature ◽  
Inadequate Response ◽  
Tnf Inhibitor ◽  
Odds Ratios ◽  
Selection For ◽  
Necrosis Factor

Background:There is an urgent need for precision medicine in targeted therapy selection for the treatment of rheumatoid arthritis (RA). TNF inhibitor (TNFi) therapies are the most prescribed targeted therapy for RA patients, yet the majority of patients fail to achieve a clinically meaningful response using this medication class. A blood-based molecular signature test evaluates RNA and clinical metrics to stratify RA patients based on their likelihood of having an inadequate response to TNFi therapies.1 Patients unlikely to respond to TNFi therapies can be directed to a different treatment option such as a JAK inhibitor, thus reducing the time needed to identify an effective therapy, improving confidence in and adherence to treatment, and increasing the patients’ chance of reaching treat-to-target goals.Objectives:High-titers of anti-cyclic citrillunated protein (anti-CCP) have been independently associated with reduced response to TNFi therapy;2 thus, we evaluated the ability of a blood-based molecular signature response classifier (MSRC) test to stratify RA patients by their likelihood of inadequate response to TNFi therapies – regardless of their positive or negative anti-CCP status.Methods:A subset of patients enrolled in the Network-04 prospective observational trial evaluating the ability of a molecular signature response classifier to stratify patients were subdivided into two groups based upon whether they were positive (N = 72) or negative (N = 74) for anti-CCP. The odds of inadequate response to TNFi therapies were calculated based on whether or not a patient had a molecular signature of non-response to TNFi therapy at baseline before the start of treatment. Odds ratios and confidence intervals were calculated3,4 to represent the strength of association between detecting the molecular signature of non-response and the patient’s failure to achieve ACR50 at 6 months.Results:The odds that a patient with a molecular signature of non-response failed to meet ACR50 criteria at 6 months was approximately three times greater than among those patients who lacked the signal (Table 1). No significant difference in odds ratios was observed between patients who were positive or negative for anti-CCP.Table 1.The odds of patients with a molecular signature of non-response failing to achieve an ACR50 response 6 months after TNF inhibitor therapy initiationOdds ratio (95% confidence interval)Anti-CCP positive3.5 (1.3-9.7)Anti-CCP negative3.1 (1.2-8.3)Conclusion:The MSRC test evaluates RA disease biology and accurately stratifies patients based on their likelihood of having an inadequate response to TNFi therapies, regardless of being negative or positive for anti-CCP autoantibodies. Rheumatologists can use the results of the MSRC test to inform targeted therapy selection for RA patients, instead of their anti-CCP serostatus, eliminating the variability inherent to the anti-CCP measurement and its inability to consistently predict TNFi therapy incompatibility. With the MSRC test, providers can rely on a more predictable and accurate assessment of TNFi therapy success or failure when coordinating patient management.References:[1]Mellors, T. et al. Clinical Validation of a Blood-Based Predictive Test for Stratification of Response to Tumor Necrosis Factor Inhibitor Therapies in Rheumatoid Arthritis Patients. Network and Systems Medicine3, 91-104, doi:10.1089/nsm.2020.0007 (2020).[2]Braun-Moscovici, Y. et al. Anti-cyclic citrullinated protein antibodies as a predictor of response to anti-tumor necrosis factor-alpha therapy in patients with rheumatoid arthritis. J Rheumatol33, 497-500 (2006).[3]Szumilas, M. Explaining odds ratios. J Can Acad Child Adolesc Psychiatry19, 227-229 (2010).[4]Sperandei, S. Understanding logistic regression analysis. Biochem Med (Zagreb) 24, 12-18, doi:10.11613/BM.2014.003 (2014).Disclosure of Interests:Stanley Cohen: None declared, Vibeke Strand Consultant of: Abbvie, Amgen, Arena, BMS, Boehringer Ingelheim, Celltrion, Galapagos, Genentech/Roche, Gilead, GSK, Ichnos, Inmedix, Janssen,Kiniksa, Lilly,Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Setpoint, UCB, Erin Connolly-Strong Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation

Longterm Safety and Efficacy of Abatacept Through 5 Years of Treatment in Patients with Rheumatoid Arthritis and an Inadequate Response to Tumor Necrosis Factor Inhibitor Therapy

2012 ◽  
Vol 39 (8) ◽  
pp. 1546-1554 ◽  
Author(s):  
MARK C. GENOVESE ◽  
MICHAEL SCHIFF ◽  
MICHAEL LUGGEN ◽  
MANUELA LE BARS ◽  
RICHARD ARANDA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Disease Activity ◽  
Physical Function ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Inhibitor ◽  
Malignant Neoplasms ◽  
Inadequate Response ◽  
Safety And Efficacy ◽  
Necrosis Factor

Objective.To evaluate abatacept safety and efficacy over 5 years in patients with rheumatoid arthritis (RA) who had inadequate response to anti-tumor necrosis factor (TNF) therapy in the ATTAIN trial.Methods.Patients completing the 6-month, double-blind (DB) placebo-controlled period were eligible to enter the longterm extension (LTE), where all patients received abatacept every 4 weeks (∼10 mg/kg, according to weight range). Safety, efficacy, physical function, and health-related quality of life were monitored throughout.Results.In total, 317 patients (218 DB abatacept, 99 DB placebo) entered the LTE; 150 (47.3%) completed it. Overall incidences of serious adverse events, infections, serious infections, malignant neoplasms, and autoimmune events did not increase during the LTE versus the DB period. American College of Rheumatology responses with abatacept at Month 6 were maintained over 5 years. At Year 5, among patients who received abatacept for 5 years and had available data, 38/103 (36.9%) achieved low disease activity as defined by the 28-joint Disease Activity Score (DAS28)/C-reactive protein (CRP); 23/103 (22.3%) achieved DAS28/CRP-defined remission. Health Assessment Questionnaire response was achieved by 62.5% of patients remaining on treatment at Year 5; mean improvements from baseline in physical component summary and mental component summary scores were 7.34 and 6.42, respectively. High proportions of patients maintained efficacy and physical function benefits or improved their disease state at each timepoint throughout the LTE, if remaining on abatacept treatment.Conclusion.Safety remained consistent, and abatacept efficacy was maintained from 6 months to 5 years, demonstrating the benefits of switching to abatacept in this difficult-to-treat population of patients with RA previously failing anti-TNF therapy.

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