Additions to Methotrexate with Conventional and Biologic Dmards in Rheumatoid Arthritis: Are There Differences in Subsequent Time to Treatment Failure?

Sasha Bernatsky¹, Orit Schieir², Cristiano S. Moura³, Marie-France Valois⁴, Susan J. Bartlett⁵, Carol A Hitchon⁶, Janet E. Pope⁷, Gilles Boire⁸, Boulos Haraoui⁹, Edward C. Keystone¹⁰, Diane Tin¹¹, Carter Thorne¹² and Vivian P. Bykerk¹³, ¹Divisions of Rheumatology and Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada, ²McGill University, Montreal, ON, Canada, ³1Division of Clinical Epidemiology, McGill University Health Centre, Montreal, QC, Canada, ⁴McGill University, Montreal, QC, Canada, ⁵Department of Medicine, Division of ClinEpi, Rheumatology, Respirology, McGill University, Montreal, QC, Canada, ⁶University of Manitoba, Winnipeg, MB, Canada, ⁷Department of Medicine, Division of Rheumatology, University of Western Ontario, St Joseph's Health Care, London, ON, Canada, ⁸Rheumatology Division, Centre Hospitalier Universitaire de Sherbrooke and Universite de Sherbrooke, Sherbrooke, QC, Canada, ⁹Institut de Rhumatologie de Montréal, Montreal, QC, Canada, ¹⁰University of Toronto, Toronto, ON, Canada, ¹¹The Arthritis Program, Southlake Regional Health Centre, Newmarket, ON, Canada, ¹²University of Toronto, Newmarket, ON, Canada, ¹³2-005, Mt Sinai Hospital, Toronto, ON, Canada

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: methotrexate (MTX) and rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 5, 2017

Title: Rheumatoid Arthritis – Clinical Aspects Poster I: Treatment Patterns and Response

Session Type: ACR Poster Session A

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

Background/Purpose: Our objective was to compare RA treatment strategies with conventional and biologic DMARDs after an initial MTX strategy was ineffective or associated with a severe adverse event.

Methods: We studied adults from a multicenter early arthritis cohort (enrolled from 2007- 2017 within one year of symptom onset). RA patients were eligible for our analyses if they initiated MTX (+/-other DMARDs) within 90 days of cohort entry and subsequently changed therapy (changed MTX route, lowered or stopped MTX or other DMARD, or added another DMARD or biologic). For this analyses, the time of medication change formed the time zero for a survival analyses of the second treatment approach. Patients were followed from time zero to assess discontinuations of, or additions to, their therapy. Multivariable survival models were used to compare outcomes. We generated hazard ratios (HRs) and 95% confidence intervals (CI), comparing each of the treatment groups to oral methotrexate monotherapy.

Results: We included 911 RA patients initially exposed to MTX who had a first treatment failure. At time zero (time of initial failure), the most common second treatment strategies were MTX+ another DMARD (32.9%) and non MTX DMARDs (26.1%) (Table 1).

Table 1 Distribution of treatment approaches after a first MTX failure

Treatment	Frequency			Time to discontinuation (in months)¹			Frequency of any failure*		Loss of efficacy²		Serious adverse effect²		Any side effect²
	N	%	Median		Range	N (%)		N (%)		N (%)		N (%)
MTX oral	58	6.4	7.8		0.3 to 69.5	39 (67%)		6 (10.3%)		0 (0%)		11 (19.0%)
MTX subcutaneous	89	9.8	9.1		0.3 to 89.8	58 (65%)		4 (4.5%)		0 (0%)		17 (19.1%)
MTX + another DMARD	300	32.9	6.8		0.3 to 83.9	196 (65%)		23 (7.7%)		1 (0.3%)		100 (33.3%)
MTX+SSZ+HCQ	126	13.8	12.0		0.3 to 83.0	82 (65%)		7 (5.6%)		0 (0%)		48 (38.1%)
Biologics+/- DMARDs including MTX	100	11.0	12.9		0.4 to 95.7	37 (37%)		11 (11.0%)		0 (0%)		22 (22.0%)
Non MTX DMARDs only	238	26.1	4.5		0.3 to 73.9	182 (76%)		6 (2.5%)		0 (0%)		45 (18.9%)
Total	911	100.0	6.9		0.3 to 95.7	594 (65%)		57 (6.3%)		1 (0.1%)		243 (26.7%)
¹ Estimated by Kaplan-Meier curves ²As reported by the treating MD

The multivariable Cox regression analysis for the 911 RA patients suggested that those on biologics and those on triple therapy had a longer time to failure, compared to the group taking MTX oral monotherapy. (Table 2)

Table 2 Adjusted hazard rations (HR) for drug changes after time zero*

Treatment at time zero	HR	95% CI
MTX subcutaneous monotherapy	0.91	0.61, 1.35
MTX + another DMARD	0.87	0.62 1.22
MTX+SSZ+HCQ	0.64	0.44, 0.94
Biologics+/- DMARDs including MTX	0.31	0.20, 0.49
Non MTX DMARDs only	1.26	0.89, 1.77

*Adjusting for baseline characteristics: age, sex, co-morbidities, symptom duration, race, education, smoking, erosions, DAS-28, disease activity, corticosteroids, NSAIDs, and COXIBs

Conclusion: Our data suggest that, in those who fail initial MTX, RA patients given biologics or triple therapy remain on that treatment longer without further changes, versus those taking augmented MTX oral monotherapy. These data do not confirm clear differences in outcomes with respect to MTX(dual or triple) combinations, but width of confidence intervals precludes definitive conclusions in this regard.

Disclosure: S. Bernatsky, None; O. Schieir, None; C. S. Moura, None; M. F. Valois, None; S. J. Bartlett, PROMIS, 6,Pflizer, UCB, Lilly, 5; C. A. Hitchon, None; J. E. Pope, AbbVie, Amgen, Bayer, BMS, Celtrion, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, UCB, 5,Amgen, Bayer, BMS, GSK, Merck, Novartis, Pfizer, Roche, UCB, 2; G. Boire, None; B. Haraoui, None; 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, Crescendo Bioscience, F. Hoffmann-La Roche Inc, Genentech Inc, Janssen Inc, Lilly Pharmaceuticals, Merck, Pfizer Pharmaceuticals, UCB, 5,Amgen, Abbott Laboratories, Astrazeneca LP, Bristol-Myers Squibb Canada,, 8; D. Tin, None; C. Thorne, AbbVie, Amgen, Celgene, Lilly, Novartis, Pfizer, Sanofi, and UCB; has served as a consultant for AbbVie, Amgen, Celgene, Centocor, Genzyme, Hospira, Janssen, Lilly, Medexus/Medac, Merck, Novartis, Pfizer, Sanofi, and UCB, 2,Medexus/Medac, 8; V. P. Bykerk, None.

To cite this abstract in AMA style:

Bernatsky S, Schieir O, Moura CS, Valois MF, Bartlett SJ, Hitchon CA, Pope JE, Boire G, Haraoui B, Keystone EC, Tin D, Thorne C, Bykerk VP. Additions to Methotrexate with Conventional and Biologic Dmards in Rheumatoid Arthritis: Are There Differences in Subsequent Time to Treatment Failure? [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/additions-to-methotrexate-with-conventional-and-biologic-dmards-in-rheumatoid-arthritis-are-there-differences-in-subsequent-time-to-treatment-failure/. Accessed .

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