Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2020 Sep;39(9):2593-2601.
doi: 10.1007/s10067-020-05008-4. Epub 2020 Mar 12.

Effectiveness of maintenance therapy with methotrexate compared with leflunomide for patients with RA having achieved disease control with both these drugs: results of a predefined sub-analysis of CareRA, a pragmatic RCT

Veerle Stouten  1 , Stijn Michiels  2 , René Westhovens  3   2 , Diederik De Cock  3 , Amy Belba  3   2 , Sofia Pazmino  3 , Kristien Van der Elst  2 , Johan Joly  2 , Patrick Verschueren  3   2
Affiliations
Randomized Controlled Trial

Effectiveness of maintenance therapy with methotrexate compared with leflunomide for patients with RA having achieved disease control with both these drugs: results of a predefined sub-analysis of CareRA, a pragmatic RCT

Veerle Stouten et al. Clin Rheumatol. 2020 Sep.

Abstract

Introduction/objectives: Evidence regarding the effectiveness of step-down strategies for patients with well-controlled early rheumatoid arthritis (RA) on a combination of methotrexate (MTX) and leflunomide (LEF) is currently lacking.

Method: The Care in early RA (CareRA) trial is a 2-year randomized pragmatic trial comparing different remission induction strategies in treatment-naïve patients with early RA. For this study, we included participants who achieved low disease activity (LDA) (DAS28-CRP ≤ 3.2) between 40 to 52 weeks after starting a combination of MTX, LEF, and a prednisone bridging scheme followed by a treat-to-target approach. Patients were re-randomized to a maintenance monotherapy of either MTX 15 mg weekly or LEF 20 mg daily. Remission rates (DAS28-CRP < 2.6) at week 65 counted from re-randomization, as well as drug retention rates and safety during the 65 weeks of follow-up, were compared.

Results: Remission rates at week 65 after re-randomization were numerically higher in patients assigned to MTX (29/32; 90.6%) compared with patients on LEF (20/27; 74.1%) (p = 0.091). Of patients assigned to MTX, 60% (19/32) maintained LDA while continuing their assigned monotherapy until week 65 after re-randomization versus 44% (12/27) in the LEF group (p = 0.25). Patients re-randomized to MTX were more frequently in LDA measured by Clinical Disease Activity Index (32/32; 100%) compared with patients on LEF (23/27; 85.2%) (p = 0.024) 65 weeks after re-randomization. According to survival analyses, the probability of maintaining MTX monotherapy was higher (81%) than maintaining LEF monotherapy (55%) for 65 weeks (p = 0.025) after re-randomization. Safety analysis after re-randomization showed a good safety profile in both groups.

Conclusion: MTX monotherapy seems not significantly more efficacious as maintenance treatment compared with LEF monotherapy but has a better retention rate and is well tolerated in early RA patients in LDA after combination therapy with both.

Trial registration: Clinical trials NCT01172639 Key points • Methotrexate should be preferred over leflunomide as maintenance therapy after an initial intensive combination of these two drugs. • Methotrexate shows a better retention rate to leflunomide as maintenance therapy in this context.

Keywords: Leflunomide; Maintenance therapy; Methotrexate; Monotherapy; Rheumatoid.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

  • Therapeutic Maintenance Level of Methotrexate in Rheumatoid Arthritis: A RBSMR Study.
    Oulkadi L, Rostom S, Hmamouchi I, Binoune IE, Amine B, Abouqal R, Achemlal L, Allali F, Bouchti IE, Maghraoui AE, Ghozlani I, Hassikou H, Harzy T, Ichchou L, Mkinsi O, Niamane R, Bahiri R. Oulkadi L, et al. Mediterr J Rheumatol. 2022 Jun 30;33(2):224-231. doi: 10.31138/mjr.33.2.224. eCollection 2022 Jun. Mediterr J Rheumatol. 2022. PMID: 36128204 Free PMC article.

References

    1. Emery P, Breedveld FC, Lemmel EM, Kaltwasser JP, Dawes PT, Gomor B et al (2000) A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology (Oxford) 39(6):655–665
    1. Jones PB, White DH (2010) Reappraisal of the clinical use of leflunomide in rheumatoid arthritis and psoriatic arthritis. Open Access Rheumatol 2:53–71 - PubMed - PMC
    1. Mladenovic V, Domljan Z, Rozman B, Jajic I, Mihajlovic D, Dordevic J, Popovic M, Dimitrijevic M, Zivkovic M, Campion G (1995) Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis. Results of a randomized, placebo-controlled, phase II study. Arthritis Rheum 38(11):1595–1603 - PubMed
    1. Schultz M, Keeling SO, Katz SJ, Maksymowych WP, Eurich DT, Hall JJ (2017) Clinical effectiveness and safety of leflunomide in inflammatory arthritis: a report from the RAPPORT database with supporting patient survey. Clin Rheumatol 36(7):1471–1478 - PubMed
    1. Scott DL, Smolen JS, Kalden JR, van de Putte LB, Larsen A, Kvien TK, Schattenkirchner M, Nash P, Oed C, Loew-Friedrich I, European Leflunomide Study Group (2001) Treatment of active rheumatoid arthritis with leflunomide: two year follow up of a double blind, placebo controlled trial versus sulfasalazine. Ann Rheum Dis 60(10):913–923 - PubMed - PMC

Publication types

Associated data