Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Multi-Centre, Cross-Sectional, Observational Study of the Safety of Methotrexate and Leflunomide in Combination in the Treatment of Patients with Rheumatoid Arthritis The SMILE StudySafety ofMethotrexateIn Combination withLeflunomide.

Bird2,  Paul, Griffiths1,  Hedley, The Optimising Patient Outcomes in Australian RheumatoLogy [OPAL] Consortium,  

Barwon Rheumatology Service, Victoria, Australia
Combined Rheumatology Practice (CRP), University of NSW, Sydney, NSW, Australia

Background:

The combination of methotrexate and leflunomide is effective in early RA[1] and commonly utilized in Australia. The frequency of use of this combination in Australia is in part due to Federal government legislation, mandating the combination as pre-requisite treatment prior to eligibility for government funded biological therapy. Hepatotoxicity and neutropenia are two of the most common adverse effects associated with this combination.

The primary objective of this study was to assess the safety of treating patients with rheumatoid arthritis with a combination of methotrexate (MTX) and leflunomide (LEF) in comparison to methotrexate monotherapy (MTX).

Methods:

Multi-centre, observational, cross-sectional, retrospective, safety study. The study was conducted by the OPAL QUMI (Optimising Patient outcomes in Australian rheumatoLogy – Quality Use of Medicines Initiative). Using a clinical audit program, data was sourced from 12 participating rheumatology practices comprising 24 rheumatologists. All data was de-identified to patient, clinic and clinician prior to collection. Approval for the study was granted by the University of New South Wales Human Research Ethics Committee.

Results:

In total, 3362 patients were included in the study; 72% female, 27% male, <1% gender unassigned, mean age 62 years (SD 13.8). Distribution of therapy: MTX monotherapy 49.2%, LEF monotherapy 7.6%, MTX/LEF 14.8%, Neither MTX or LEF 28.4%.

Mean MTX dose in the monotherapy group was 14 mg/week (SD 6.7), mean MTX dose in the MTX/LEF combination group 18 mg (SD 17). Mean LEF dose in the monotherapy group was 16.8 mg/day (SD 4.9), mean LEF dose in the MTX/ LEF combination group was 16.0 (SD 5.3). Co-morbid liver disease was reported in less than 5% of patients.

Liver function abnormalities were reported in 12% of the MTX monotherapy group, 16% of the LEF monotherapy group, 14% of the MTX/LEF combination group and 16% of the group taking neither of the drugs. The majority of the AST/ALT abnormalities were in the range less than 1.5 times the upper limit of normal in all four groups.

Neutropenia was reported in 2% of the MTX monotherapy group, 8% of the LEF monotherapy group, 5% of the MTX/LEF combination group and 3% of the group not taking either drug.

Conclusion:

Liver function abnormalities and neutropenia in the MTX/LEF combination group were mild and equivalent to reported levels in either MTX monotherapy or LEF monotherapy. Levels of liver function abnormalities in the combination group were lower than those reported in previously published trials.[2] The combination of MTX and LEF was well tolerated, with adverse events comparable to monotherapy and the other non biologic DMARD treatment group.

[1]Kremer, J, et al. JRheumatol 2004;Aug 31(8): 1521-31

[2]Lee, SS et al. ScandJRheum 2009 Jan-Feb;38(1):11-14

To cite this abstract, please use the following information:
Bird, Paul, Griffiths, Hedley, The Optimising Patient Outcomes in Australian RheumatoLogy [OPAL] Consortium, ; Multi-Centre, Cross-Sectional, Observational Study of the Safety of Methotrexate and Leflunomide in Combination in the Treatment of Patients with Rheumatoid Arthritis The SMILE StudySafety ofMethotrexateIn Combination withLeflunomide. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :319
DOI: 10.1002/art.28088

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2010 ACR/ARHP