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.

Methotrexate and Leflunomide Combination Therapy Is a Safe and Effective Alternative to Methotrexate and Etanercept in JIA.

Borzutzky1,  Arturo, Lagunas2,  Tamy, Zurakowski2,  David, Sundel3,  Robert P.

Children's Hospital Boston, Boston, MA
Children's Hospital Boston
Childrens Hosp Medical Center, Boston, MA


Methotrexate combined with TNF-inhibitors is generally regarded as the most effective treatment for recalcitrant juvenile idiopathic arthritis (JIA). Ongoing studies are evaluating the possibility that this should be first-line treatment in some situations. TNF inhibitors, however, are currently available only as parenteral formulations, and they are associated with significant immunosuppression, an increased risk of opportunistic infections, and possibly an increased risk of malignancies. These factors make the combination less than ideal for treating children with JIA. Combination therapy with methotrexate and leflunomide (MTX-LEF) has been shown to be effective in active rheumatoid arthritis as an alternative to the use of biologic agents. However, there is little information on the use of this combination in JIA.


To compare the efficacy and safety of MTX-LEF to that of MTX and etanercept (MTX-ETN) in children with polyarticular JIA incompletely responsive to MTX or LEF monotherapy.


We retrospectively reviewed the clinical data of children with JIA treated at a single tertiary care children's hospital between 1999 and 2009. We compared outcomes and adverse events in patients treated with combination MTX-LEF to those treated with MTX-ETN after failure of methotrexate monotherapy. Inactive disease was defined as absence of active arthritis and normal inflammatory parameters. Remission was defined as 6 months of inactive disease.


56 patients met inclusion criteria: 25 patients treated with MTX-LEF and 31 patients treated with MTX-ETN were available for evaluation. Groups did not differ significantly for age, sex, race, time from diagnosis to combination therapy, follow-up length, JIA subtype, initial joint count or initial ESR (Table 1). Outcomes and significant adverse events did not differ significantly between the two groups after a mean follow-up of 20.5 ± 13 months. No serious adverse events were identified in any of the treatment groups. Inactive disease was achieved in 52% of the MTX-LEF group and 61.3% of the MTX-ETN group (P = 0.59). Remission was achieved in 28% of the MTX-LEF group and 35.5% of the MTX-ETN group (P = 0.58). Kaplan-Meier survival distributions for time to inactive disease and to remission were comparable between groups (P=0.94 and P=0.86, respectively).


In a retrospective pilot study of 56 children with JIA, MTX-LEF was a safe and effective alternative to MTX-ETN in patients with arthritis refractory to DMARD monotherapy. Lower costs, availability of oral dosing, and an absence of risk of opportunistic infections or malignancies favor the use of combination DMARDs over biologics. Randomized controlled trials are necessary to evaluate this prospectively.

Table 1. Clinical characteristics of patients.

CharacteristicMTX+LEF (n = 25)MTX+ETN (n = 31)P
Age, mean ± SD12 ± 5.210.55 ± 5.10.3
Female sex, %72840.34
Race (% white)84%90.3%0.56
Diagnosis to combination therapy (months)56.7 ± 5047.9 ± 440.49
Duration of follow-up (months)18.5 ± 11.722.1 ± 13.90.3
ILAR JIA diagnosis  0.81
  Polyarthritis (RF+)16%16% 
  Polyarthritis (RF-)56%42% 
  Psoriatic arthritis16%19% 
  Enthesitis related arthritis8%13% 
Initial joint count, mean ± SD8.5 ± 8.66.7 ± 6.90.37
Initial ESR, mean ± SD12.9 ± 9.613.9 ± 14.50.77

To cite this abstract, please use the following information:
Borzutzky, Arturo, Lagunas, Tamy, Zurakowski, David, Sundel, Robert P.; Methotrexate and Leflunomide Combination Therapy Is a Safe and Effective Alternative to Methotrexate and Etanercept in JIA. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :229
DOI: 10.1002/art.27998

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