Morgan Schultz 1, Stephanie Keeling 2, Steven Katz 2, Walter Maksymowych 2, Dean Eurich 3, Jill Hall 1 1

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1 Morgan Schultz 1, Stephanie Keeling 2, Steven Katz 2, Walter Maksymowych 2, Dean Eurich 3, Jill Hall 1 1 Faculty of Pharmacy and Pharmaceutical Sciences, 2 Faciluty of Medicine and Dentistry, 3 School of Public Health, University of Alberta Presented by: Morgan Schultz BSc(Pharm), PharmD Student University of Alberta September 12 th, 2015

2 Presenter Disclosure Presenter s Name: Morgan Schultz I have no current or past relationships with commercial entities Speaking Fees for current program: I have received no speaker s fee for this learning activity

3 Commercial Support Disclosure This program has received no financial or in-kind support from any commercial or other organization

4 Objectives To inform pharmacists of a research project being completed in the area of rheumatology at the University of Alberta To describe the proportion of patients self reporting achievement of a clinically meaningful response with leflunomide therapy To inform pharmacists of reported side effects and discontinuation rates with leflunomide in patients with rheumatoid arthritis

5 Background Leflunomide is a disease modifying anti-rheumatic drug (DMARD) Indicated for treatment of rheumatoid arthritis

6 Canadian Rheumatology Association Recommendations

7 Problem In 7 of 10 provinces, including Alberta, patients must fail leflunomide therapy prior to receiving provincial drug coverage of biologic DMARDs However, no guidelines (Canadian, American, European) specifically recommend that leflunomide should be trialled before initiating biologic therapy Risks of leflunomide therapy: Hepatic toxicity Led to FDA Black Box warning in 2010

8 Research Objectives To assess the proportion of patients achieving a clinically meaningful response with leflunomide at 3 months Defined as remission or low disease activity To assess the proportion of patients experiencing adverse effects (AEs) including: Those requiring therapy discontinuation Description of adverse effects Infections Liver toxicities

9 Methods Development of selfreported, standardized questionnaire Selection of populationbased cohort from RAPPORT database Distribution to n = 1,956 recipients during February & March 2015 RAPPORT: Rheumatoid Arthritis Pharmacovigilance Program

10 Results N = 714 completed the survey 36.5% response rate Of those who provided information regarding type of inflammatory arthritis: 82.6% had Rheumatoid Arthritis 15.7% had Psoriatic Arthritis The majority (72.4%) reported an initial dose of 20mg daily The majority (97.4%) reported previously taking methotrexate Of the 392 respondents who disclosed their insurance coverage: 22% reported having Alberta Blue Cross coverage

11 Clinical Response Of the 395 respondents who reported taking leflunomide for at least 3 months: 38% reported a clinical response Defined as remission or low disease activity

12 Discontinuation Rates Of the 407 respondents, 236 (58%) discontinued therapy Of those who reported rationale for discontinuation (n=230): 36.1% discontinued due to AEs 28.7% discontinued due to lack of efficacy 24.8% discontinued due to both AEs and lack of efficacy

13 Adverse Effects Of the 226 respondents that described their adverse effects: 52.2% reported nuisance side effects (hair loss, nausea, stomach pain) 38.5% reported diarrhea 7.1% reported liver toxicity 5.8% reported a serious infection

14 Discussion & Conclusion Achievement of a clinically meaningful response with leflunomide was self-reported by a minority of survey respondents, with a greater proportion reporting AEs Serious AEs were rare, however a substantial number of patients discontinued leflunomide due to AEs Current policies requiring failure of leflunomide therapy prior to coverage of biologic DMARDs should be reassessed

15 References Bykerk VP, Akhavan P, Hazlewood GS, et al. Canadian Rheumatology Association recommendations for pharmacological management of rheumatoid arthritis with traditional and biologic disease-modifying antirheumatic drugs. J Rheumatol. 2012;39(8): doi: /jrheum Singh J a, Furst DE, Bharat A, et al update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Am Coll Rheumatol. 2012;64(5): doi: /acr Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010;69: doi: /ard Pease C, Pope JE, Thorne C, et al. Canadian variation by province in rheumatoid arthritis initiating anti-tumor necrosis factor therapy: Results from the optimization of adalimumab trial. J Rheumatol. 2010;37: doi: /jrheum FDA.gov. FDA Drug Safety Communication: New boxed warning for severe liver injury with arthritis drug Arava (leflunomide) viders/ucm htm. Accessed February 24, de Vries ST, Mol PG, de Zeeuw D, Haaijer-Ruskamp FM, Denig P. Development and Initial Validation of a Patient-Reported Adverse Drug Event Questionnaire. Drug Saf Apr 4. [Epub ahead of print].