Association of mycophenolate and azathioprine use with cognitive function in systemic lupus

Author:

Dobrowolski Chrisanna1,McGinley John2,Fazzari Melissa3,Su Jiandong4,Bingham Kathleen S5,Anderson Nicole4,Ruttan Lesley6,Beaton Dorcas E7,Wither Joan E4,Tartaglia Maria Carmela8,Kakvan Mahta4,Bonilla Dennisse4,Choi May Y9ORCID,Fritzler Marvin J9ORCID,Diaz Martinez Juan Pablo4,Katz Patricia10,Green Robin6,Putterman Chaim11121314,Touma Zahi4ORCID

Affiliation:

1. Division of Rheumatology, Icahn School of Medicine at Mount Sinai , New York, NY, USA

2. Department of Neurology, Albert Einstein College of Medicine , Bronx, NY, USA

3. Department of Epidemiology and Population Health and Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine , Bronx, NY, USA

4. University of Toronto Lupus Clinic, Centre for Prognosis Studies in Rheumatic Diseases, Toronto Western Hospital , Toronto, ON, Canada

5. Centre for Mental Health, University Health Network; Department of Psychiatry, University of Toronto , Toronto, ON, Canada

6. University Health Network-Toronto Rehabilitation Institute , Toronto, ON, Canada

7. Institute for Work and Health, University of Toronto , Toronto, ON, Canada

8. University of Toronto Krembil Neurosciences Centre , Toronto, ON, Canada

9. Cumming School of Medicine, University of Calgary , Calgary, AB, Canada

10. University of California, San Francisco , Novato, CA, USA

11. Department of Microbiology and Immunology, Albert Einstein School of Medicine , Bronx, NY, USA

12. Division of Rheumatology, Albert Einstein College of Medicine , Bronx, NY, USA

13. Azrieli School of Medicine , Safed, Israel

14. Galillee Medical Center , Nahariya, Israel

Abstract

Abstract Objectives Cognitive dysfunction (CD) is a common manifestation of SLE that can have detrimental consequences for those affected. To date, no treatments have been approved for SLE-CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given that these medications have demonstrated neuroprotective qualities in prior studies. Methods Consecutive adult SLE patients presenting to a single healthcare center were considered for participation. The ACR neuropsychological battery for SLE was administered to consenting patients at 0, 6 and 12 months. Scores were compared with age- and sex-matched controls. Primary outcome was CD, defined as a z-score ≤−1.5 in two or more cognitive domains. Mixed-effects logistic regression models were constructed to estimate the odds of CD with respect to AZA and MMF use. Results A total of 300 participants representing 676 patient visits completed the study; 114 (38%) met criteria for CD at baseline. The cumulative AZA dose (g/kg) was associated with reduced odds of CD [odds ratio (OR) 0.76 (95% CI 0.58, 0.98), P = 0.04]. Years of AZA treatment was also associated with reduced odds of CD [OR 0.72 (95% CI 0.54, 0.97), P = 0.03]. MMF use was not associated with CD. Conclusion AZA use was associated with significantly lower odds of SLE-CD, while MMF use was not. Additional studies are warranted to further investigate the relationship of AZA and SLE-CD.

Funder

National Institutes of Health

National Center for Advancing Translational Science

Arthritis Society of Canada, Canadian Institutes of Health Research, Physician’s Services Incorporated

Province of Ontario Early Research Award

Lupus Research Alliance

Arthritis Society, Young Investigator Award

Canadian Rheumatology Association–Arthritis Society Clinician Investigator Award

Department of Medicine, University of Toronto

Lupus Ontario and Schroeder Arthritis Institute

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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