Post-market drug safety and effectiveness in ankylosing spondylitis (AS)

Query 10-22b: The effects of Disease-Modifying Anti-Rheumatic Drugs (DMARDs) in Ankylosing Spondylitis (AS)

Ankylosing spondylitis (AS) is a chronic, progressive, inflammatory type of arthritis that affects up to 1 percent of Canadians. Therapy options are limited, especially for patients with active and severe disease. Nonsteroidal anti-inflammatory drugs (NSAIDs, e.g. Naproxen) are used along with disease-modifying anti-rheumatic drugs (DMARDs, e.g. methotrexate).

Unfortunately there is relatively little published evidence to help physicians and their patients choose which DMARDs to use in which AS patients, under which circumstances. In this catalyst grant, we based our analyses on data prospectively collected on patients enrolled in a large AS patient cohort.

The main clinical outcomes are measured by validated measures of disease activity, functional limitation, and quality of life. Data on infections requiring hospitalizations are being used to evaluate safety.

We presented the results at the Canadian Rheumatology Association (CRA) meeting in Quebec City, Quebec in February 2015, and the EUropean League Against Rheumatism (EURLA) meeting in Rome, Italy in June 2015.

Moura et al. Persistence of Anti-TNF and nbDMARD use in a Population-Based Sample of Ankylosing Spondylitis in Quebec. JRheum #40 Canadian Rheumatology Association (CRA) Annual Scientific Meeting. Quebec City, Canada. 4-7 February 2015.

Moura et al. Risk of hospitalized serious infection in spondylitis ankylosing patients using nbDMARD or Anti-TNF.  Ann rheum dis 2015; 74(suppl2): 266. Annual European Congress of Rheumatology EULAR. Rome, Italy. 10-13 June 2015.

Moura C, Rahme E, Maksymowych W, Abrahamowicz M, Bessette L, Bernatsky S. Use of disease-modifying anti-rheumatic or anti-tumour necrosis factor drugs and risk of hospitalized infections in ankylosing spondylitis (AS).  Scandinavian Journal of Rheumatology. 2018 Aug;1-7.

For more information contact: Autumn Neville. Research Coordinator. [email protected]   514.934.1934 ext.44844 or ext.44718

Newer antidepressants and pediatric pulmonary hypertension

Query 12-10: Newer antidepressants and Persistent Pulmonary Hypertension of the Newborn (PPHN)

This project was funded (by CIHR-DSEN, as a query posed by Health Canada) on November 2013 for one year (Nominated PI A. Berard, co-PI S. Bernatsky, co-investigator M. Abrahamowicz).

In our analyses, we used data from three pre-established pregnancy cohorts (Quebec, Saskatchewan and US Medicaid). At present, all three cohorts have been built using a similar protocol and all variables have been defined (exposure, outcome and covariates/confounders).

Results were discussed at the June 2015 Reseau Quebecois de Recherche sur les Medicaments (RQRM) meeting and the International Society for Pharmacoepidemiology (ICPE) meeting in August 2015.

Our manuscript has been published:

Berard A, Sheehy O, Zhao JP,Vinet E, Bernatsky S, Abrahamowicz M. SSRI and SNRI use during pregnancy and the risk of persistent pulmonary hypertension of the newborn. Br J Clin Pharmacol. 2017 May;83(5):1126-1133.

For more information contact: Autumn Neville. Research Coordinator. [email protected]   514.934.1934 ext.44844 or ext.44718

Darunavir and congenital malformations

Query 13-01: Darunavir and congenital malformations

This project was funded (by CIHR-DSEN, as a query posed by Health Canada) in August 2013 for one year (PI: A. Berard, co-PI S. Bernatsky, co-investigator M. Abrahamowicz).

In our analyses, we used data from three pre-established pregnancy cohorts (Quebec, Saskatchewan and US Medicaid). Results indicated that antiretroviral use during the first trimester of pregnancy was increasing the risk of gastrointestinal defect and genital organ defects.

Results were discussed at the June 2015 Reseau Quebecois de Recherche sur les Medicaments (RQRM) meeting and the Teratology Society meeting in June 2015.

Our manuscript has been accepted for publication:

Berard A, Sheehy O, Zhao J, Abrahamowicz M, Loutfy M, Boucoiran I, Bernatsky S. Antiretroviral combination use during pregnancy and the risk of major congenital malformations. AIDS. 2017 Oct;31(16):2267-2277.

For more information contact: Autumn Neville. Research Coordinator. [email protected]   514.934.1934 ext.44844 or ext.44718

Insulin glargine vs NPH insulin in type 1 diabetes mellitus & Sitagliptan vs NPH insulin in type 2 diabetes mellitus

Query 11-04: How does real world use of insulin glargine compare to NPH insulin in terms of effectiveness and safety (and ideally cost-effectiveness) for the management of type 1 diabetes mellitus? What is the comparative effectiveness and safety of sitagliptan and NPH insulin for the management of type 2 diabetes (T2D) not controlled by metformin plus sulfonylurea?

This project was originated with a query by British Columbia Ministry of Health in 2013 and funded for 3 years.

Final analysis using Marketscan for both parts of this query were finalized. With T1DM, we found that initiators of NPH insulin were more likely to switch to another insulin therapy after discontinuation (HR: 1.51; 95% CI 1.27-1.79) when compared to initiators of insulin glargine. The risk of hypoglycemia, DKA, and microvascular complications was not significant different among NPH and glargine initiators. With T2DM analysis, we found that initiators of NPH insulin discontinued earlier and have three times higher risk of hypoglycemia when compared to DPP-4 users.

Moura et al. Rates of therapy switching is higher among initiators insulin glargine versus of insulin NPH in a population-based type 1 diabetes mellitus cohort. 2016 (ICPE abstract)

Moura et al. Treatment discontinuation and rates of hypoglycemia in type 2 diabetes patients treated with dipeptidyl peptidase-4 (DDP4) inhibitors or NPH insulin as third line therapy. 2016 (ICPE abstract)

Moura et al. Treatment discontinuation and clinical events in type 2 diabetes patients treated with dipeptidyl peptidase-4 inhibitors or NPH insulin as third-line therapy. Journal of Diabetes Research, 2018: 4817178.

Elharram M et al. Novel glucose-lowering agents are associated with a lower risk of cardiovascular and adverse events in type-2 diabetes: a population-based analysis. (Manuscript in preparation)

Elharram M et al. Novel glucose-lowering agents are associated with a lower risk of cardiovascular and adverse events in type-2 diabetes: a population-based analysis. Abstract – Moderated Presentation. Canadian Cardiovascular Congress (CCC), Toronto, Ontario, October 20-23, 2018.

Elharram M et al. Risk of cardiovascular events in type-2 diabetes patients initiating novel glucose lowering drugs: a population-based analysis. Oral Presentation. McGill Cardiovascular Research Day, Jewish General Hospital, Montreal, Quebec, May 2, 2018.

Raparelli V et al. Sex differences in effectiveness of glucose-lowering drugs in type-2 diabetics requiring second-line agents. (Manuscript in preparation)

For more information contact: Autumn Neville. Research Coordinator. [email protected]   514.934.1934 ext.44844 or ext.44718

SSRI and risk of fracture

Q# 11-06: Serotonin reuptake inhibitors and risk of fracture 

This project, that originated with a query by Health Canada, was funded in March 2013 (PI: Sasha Bernatsky) and is already completed.

To respond to this query, our team ensured access to the CaMos (Canadian Multicentre Osteoporosis Study) database.

We presented preliminary results at the CAPT Conference in November 2013.

Moura C, Bernatsky S, Rahme E, Beauchamp M-E, Bessette L, Adachi J, Papaioannou A, Goltzman D, Prior J, Kreiger N, Towheed T, Leslie W, Kaiser, Pickard L, Ioannidis, Fraser L-A, Abrahamowicz M. Psychotropic medication use and 10-year incident fracture risk in men and women ages 50 and older in the population-based Canadian Multicentre Osteoporosis Study (CaMOS). CAPT – ATCP Conference in Toronto, Montreal, QC, November 17-19, 2013.

Since then, our results have been presented and approved by the Health Canada.

We also prepared and published a manuscript in the high-ranking journal Osteoporosis International in January 2014.

Our results lend additional support to the hypothesis that SSRI/SNRI use is associated with an increased risk of fragility fractures. Given the high prevalence of antidepressants use, and the impact of fractures on health, our findings may have a significant clinical impact.

For more information contact: Autumn Neville. Research Coordinator. [email protected]   514.934.1934 ext.44844 or ext.44718