Safety Profile Of Methotrexate And Leflunomide In Rheumatoid Arthritis

Authors

  • Fuad Shaikh
  • Rabia Arshad
  • Nasim Karim

Keywords:

Rheumatoid arthritis, Methotrexate, Leflunomide, Laboratory parameters, Adverse effects

Abstract

Objective: To compare the safety profile of Methotrexate and Leflunomide in patients of rheumatoid arthritis. Material and Methods: A 24-week, single-blind, interventional, study was carried out on 274 patients of either sex, aged 29-69 years, diagnosed to have rheumatoid arthritis. One group was given tablet Methotrexate, 10 mg (four 2.5 mg tablets), once weekly and the other was put on tablet Leflunomide, 20 mg, once daily, orally. At each follow up laboratory parameters (Hb%, TLC, ESR, PC, SGPT,S Creatinine) and adverse effects were evaluated. Results: Of the 274 patients, 126 were on Methotrexate (70.63 % females, 61.11% RF positive, mean age 45.57 + 10.32 years) and 148 on Leflunomide (79.72 % females, 73.64 % RF positive, mean age 46.35 + 9.68 years). Laboratory parameters (TLC, SGPT, creatinine) between the two groups showed statistically significant results at the end of the study. Nausea was seen in 30.2% & 10.8% patients at 6 weeks and 5.6% and 0% at 24 weeks in the Methotrexate and Leflunomide groups respectively while alopecia was seen in 0% & 19.6% patients at 6 weeks and 1.6% & 24.3% at 24 weeks in the Methotrexate and Leflunomide groups respectively. All values were significant statistically. Conclusion: Leflunomide was found to have a better safety profile than Methotrexate as it produced greater improvement in laboratory parameters with lesser adverse effects in comparison to the traditionally used, first-choice, drug Methotrexate. 

References

Allaire SH, Prashker MJ, Meenan RF. The costs of rheumatoid arthritis. Pharmaco Economics 1994; 6:513–22.

Del Puente A, Knowler WC, Pettit DJ, Bennett PH. High incidence and prevalence of rheumatoid arthritis in Pima Indians. Am J Epidemiol 1989; 129:1170-8

Akhter E, Bilal S, Kiani A, Haque U. Prevalence of arthritis in India and Pakistan: a review. Rheumatol Int 2011; 31(7): 849-55.

Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L. A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum. 2004; 50:3085-92.

Álvarez-Lafuente R, Fernández-Gutiérrez B, Miguel S de, Jover JA, Rollin R, Loza E et al. Potential relationship between herpes virus and rheumatoid arthritis: analysis with quantitative real-time polymerase chain reaction. Annals of the Rheumatic Diseases. 2005; 64:1357-9.

Turesson C., O'Fallon WM, Crowson CS, Gabriel SE, Matteson EL. "Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years". Ann. Rheum. Dis. 2003; 62 (8): 722–7.

Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. “The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis”. Arthritis Rheum. 1988; 31 (3): 315-24.

Rantalaiho V, Korpela M, Hannonen P, Kautiainen H, Jarvenpaa S, Hakala M et al. The good initial response to therapy with a combination of traditional disease-modifying anti-rheumatic drugs is sustained over time: the eleven-year results of the Finnish rheumatoid arthritis combination therapy trial. Arthritis Rheum. May 2009; 60(5):1222-31

Emery P, Breedveld FC, Lemmel EM, Kaltwasser JP, Dawes PT, Gömör B et al. A comparison of the efficacy & safety of Leflunomide and Methotrexate for the treatment of rheumatoid arthritis. Rheumatology. 2000; 39(6)655-65.

Smolen JS, Kalden JR, Scott DL and the European Leflunomide Study Group. Efficacy and safety of Leflunomide compared with placebo and sulphasalazine in active rheumatoid arthritis: a double-blind, randomized, multicentre trial. Lancet. 1999; 353: 259–66.

Ishaq M, Muhammed JS, Hameed K, Mirza AI. Leflunomide or Methotrexate? Comparison of clinical efficacy and safety in low socio-economic rheumatoid arthritis patients. Mod Rheumatol. 2011 Aug; 21(4):375-80.

Hansen KE, Cush J, Singhal A, Cooley DA, Cohen S, Patel SR et al. The Safety and Efficacy of Leflunomide in Combination with Infliximab in Rheumatoid Arthritis. Arthritis & Rheumatism (Arthritis Care & Research) 2004 April 15; 51(2): 228 –32

Rau R, Herborn G. Benefit and risk of methotrexate treatment in rheumatoid arthritis. Clin Exp Rheumatol, 2004; 22 (Suppl. 35): S83-94.

Chopra A, Saluja M, Lagu-Joshiv V, Sarmukadam S. Leflunomide is a useful DMARD in Indian (Asian) patients. A clinic based observational study of 1 year treatment. Clin Rheumatol. 2008; 27(8):1039–44

Attar SM. Adverse effects of low dose methotrexate in rheumatoid arthritis patients. A hospital-based study. Saudi Med J. 2010 Aug; 31(8):909-15.

Curtis JR, Beukelman T, Onofrei A, Cassell S, Greenberg JD, Kavanaugh A et al. Elevated Liver Enzyme Tests Among Rheumatoid Arthritis and Psoriatic Arthritis Patients treated with Methotrexate and/or Leflunomide. Ann Rheum Dis. 2010 January; 69(1): 43-7

Beyeler C, Reichen J , Thomann SR. Quantitative liver function in patients with rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study. Br J Rheumatol. 1997; 36:338-44.

Weinblatt ME, Kaplan H, Germain BF. Low- dose methotrexate compared with auranofin in adult rheumatoid arthritis: a thirty-six-week, double-blind trial. Arthritis Rheum. 1990; 33:330-8

Kremer J, Genovese M, Cannon GW, Cush J, Furst D. Combination leflunomide and methotrexate (MTX) therapy for patients with active rheumatoid arthritis failing MTX monotherapy: open-label extension of a randomized, double-blind, placebo controlled trial. J Rheumatol. 2004; 31(8):1521–31

Morgan SL, Baggott JE, Vaughn WH. Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med. 1994; 121:833–41

Ortiz Z, Shea B, Suarez-Almazor ME, Moher D, Wells GA, Tugwell P. The efficacy of folic acid and folinic acid in reducing methotrexate gastrointestinal toxicity in rheumatoid arthritis. A meta-analysis of randomized controlled trials. J Rheumatol. 1998; 1:36–43.

Hoekstra M, van Ede AE, Haagsma CJ, Van de laar MA, Huizinga TW, Kruijsen MW et al. Factors associated with toxicity, final dose, and efficacy of Methotrexate in patients with rheumatoid arthritis. Ann Rheum Dis. 2003; 62: 423-6

Ahmed NM, Farman S, Saeed MA, Hameed R, Umair M, Ghafoor E. Leflunomide in Pakistani patients with rheumatoid arthritis: prospective study in daily rheumatology practice. International Journal of Rheumatic diseases. 2011; 14:48-54

Kalden JR, Schattenkirchner M, Sorensen H, Emery P, Deighton C, Rozman B et al. The Efficacy and Safety of Leflunomide in Patients with Active Rheumatoid Arthritis; A Five-Year Follow-up Study. Arthritis & Rheumatism. 2003; 48(6):1513–20

Silverman E, Mouy R, Spiegel L, Jung LK, Saurenmann RK, Lahdenne P et al. Leflunomide in Juvenile Rheumatoid Arthritis (JRA) Investigator Group, Leflunomide or Methotrexate for Juvenile Rheumatoid Arthritis. N Engl J Med. 2005; 352:1655-66

Buhroo AM, Baba AN. Adverse Effects of Low-Dose Methotrexate in Patients with Rheumatoid Arthritis. IJPMR October 2006; 17 (2): 21-5

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Published

2015-03-03

How to Cite

Shaikh, F. ., Arshad, R., & Karim, N. (2015). Safety Profile Of Methotrexate And Leflunomide In Rheumatoid Arthritis. Journal of Bahria University Medical and Dental College, 5(1), 20–24. Retrieved from https://jbumdc.bahria.edu.pk/index.php/ojs/article/view/98

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