What Is the Rate of Primary and Secondary Failure of Anti-TNF in RA Patients? Data from a Rheumatoid Arthritis Cohort

Edward C. Keystone¹, Mohammad Movahedi^2,3, Angela Cesta², Xiuying Li², Sandra Couto², Emmanouil Rampakakis³, John S. Sampalis^3,4, Claire Bombardier^2,5,6 and OBRI Investigators, ¹The Rebecca MacDonald Centre For Arthritis, Mount Sinai Hospital, Toronto, ON, Canada, ²Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada, ³JSS Medical Research, St-Laurent, QC, Canada, ⁴McGill University, Montreal, QC, Canada, ⁵University of Toronto, Department of Medicine (DOM) and Institute of Health Policy Management, and Evaluation (IHPME), Toronto, ON, Canada, ⁶Division of Rheumatology, Mount Sinai Hospital, Toronto, ON, Canada

Meeting: ACR/ARHP Annual Meeting 2015

Date of first publication: September 29, 2015

Keywords: Anti-TNF therapy and rheumatoid arthritis, Biologics, DMARDs, treatment

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Small Molecules, Biologics and Gene Therapy Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Although the majority of RA patients respond to treatment with anti-TNF agents, some patients present with refractory disease (1ry failure) while others show some initial clinical response and eventually lose responsiveness (2ry failure). Assessing primary and secondary failure, and thus the extent of non-response to anti-TNF agents, is complex due to the use of different definitions and variations in the timing of patient assessment in routine clinical care. The purpose of this analysis was to assess the rate of non-response based on different definitions among RA patients treated with anti-TNF in a large observational cohort.

Methods: Patients enrolled in the Ontario Best Practices Research Initiative (OBRI) that were treated with an anti-TNF agent and had available information on treatment discontinuation were included in the analysis. Those who discontinued anti-TNF due to 1ry failure, 2ry failure, or an adverse event (AE) as per the judgment of the treating physician were classified in three different types of failure, based on (i) time of failure (<6 months, 6-12 months, >12 months); (ii) response to treatment, i.e. whether they achieved DAS28 low disease activity (LDA) prior to discontinuation, and; (iii) time and response criteria. Time to treatment discontinuation and time to LDA were assessed with the Kaplan-Meier (K-M) estimator of the survival function.

Results:

953 patients (81.6% female) were included with a mean (SD) age at OBRI enrolment of 56.0 (12.5) and disease duration of 9.8 (9.5). Mean (SD) disease parameters were: DAS28: 4.6 (1.2); SJC: 6.1 (5.2); TJC: 6.8 (6.5); physician global: 4.8 (2.5) cm; patient global: 5.2 (2.7) cm.

After a mean (SD) follow-up of 32.8 (30.6) months, 259 (27.2%) patients were discontinued due to some type of failure; 187 (19.6%) due to non-response and 72 (7.6%) due to safety reasons with mean (SD) K-M-based time to failure of 9.3 (0.4) years. Table 1 summarizes the incidence of each type of failure by type of definition. Among patients failing anti-TNF treatment after 12 months half achieved DAS28 LDA before failure after a median of 37 months.

Table 1: Rates of 1ry and 2ry Anti-TNF Failure Based on Different Definitions
	Failure Definition
% of patients	Time Criteria		Response Criteria		Time & Response Criteria
1ry Failure	<6 mos	5.6%	No LDA	14.9%	No LDA	14.9%
Partial Response	6-12 mos	4.5%	–	–	<12 mos + LDA or >12 mos + LDA after 12 mos	2.0%
2ry Failure	>12 mos	9.5%	LDA	4.7%	>12 mos + LDA before 12 mos	2.7%
Safety	–	–	AE	7.6%		–
Early Safety	<6 mos	3.3%	–	–	<6 mos + AE	3.3%
Intermediate Safety	6-12 mos	1.7%	–	–	6-12 mos + AE	1.7%
Late Safety	>12 mos	2.6%	–	–	>12 mos + AE	2.6%

Conclusion: The results of this analysis have shown that the rate of primary failure to anti-TNF treatment may range from 6% to 15% depending on the failure definition used highlighting the need for standardization. Furthermore, approximately half of the patients showing some initial clinical response can achieve LDA over a 3-year period.

Disclosure: E. C. Keystone, Abbott Laboratories, Amgen Inc., AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb, F. Hoffmann-La Roche Inc, Janssen Inc, Lilly Pharmaceuticals, Novartis Pharmaceuticals, Pfizer Pharmaceuticals, Sanofi-Aventis, UCB., 2,Abbott Laboratories, AstraZeneca Pharma, Biotest, Bristol-Myers Squibb Company, F. Hoffmann-La Roche Inc, Genentech Inc, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, UCB., 5,Abbott Laboratories, Astrazeneca LP, Bristol-Myers Squibb Canada, F. Hoffmann-La Roche Inc., Janssen Inc., Pfizer Pharmaceuticals, UCB, Amgen., 6; M. Movahedi, JSS Medical Research, a Contract Research Organization, 3; A. Cesta, None; X. Li, None; S. Couto, None; E. Rampakakis, JSS Medical Research, a Contract Research Organization, 3; J. S. Sampalis, JSS Medical Research, a Contract Research Organization, 3; C. Bombardier, Abbvie, Amgen, Bristol Myers Squibb, Hospira, Janssen, Roche, Pfizer, UCB, 2.

To cite this abstract in AMA style:

Keystone EC, Movahedi M, Cesta A, Li X, Couto S, Rampakakis E, Sampalis JS, Bombardier C. What Is the Rate of Primary and Secondary Failure of Anti-TNF in RA Patients? Data from a Rheumatoid Arthritis Cohort [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/what-is-the-rate-of-primary-and-secondary-failure-of-anti-tnf-in-ra-patients-data-from-a-rheumatoid-arthritis-cohort/. Accessed .

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