Safety of leflunomide plus infliximab combination therapy in rheumatoid arthritis

Clin Exp Rheumatol. 2004 May-Jun;22(3):328-30.


Objective: To analyse the safety of leflunomide plus infliximab combination therapy, in adult rheumatoid arthritis (RA) patients.

Patients: A retrospective study of 17 adult patients with active RA (DAS 28 = 5.94 +/- 0.88 at baseline) who were treated with a combination of leflunomide plus infliximab after failure of treatment with other DMARDs. 13 patients were treated for a minimum of 3 months with leflunomide without toxicity before beginning infliximab. Treatment was begun simultaneously with both drugs in 4 patients. Side effects (clinical and biological) and efficacy (DAS 28) were evaluated at each infliximab infusion (3 mg/kg at week 0, 2, 6 and then every 8 weeks).

Results: Thirteen patients experienced 20 types of side effects and 8 of them stopped the combination therapy. The causes of discontinuation were congestive heart failure (1 case), hypertension with thoracic pain (2 cases), eczematous skin patches (2 cases) and neutropenia (3 cases). No death was registered. Nine RA patients continuted the therapy with a median follow-up of 22 weeks. Only 4 of them experienced no side effects. Eight patients were positive for antinuclear antibodies (ANA) and 1 for double-stranded DNA (dsDNA) antibodies at study entry. After treatment, 13 and 5 patients tested positive respectively for ANAs and dsDNA antibodies. There was no relationship between discontinuation and ANA/dsDNA positivity.

Conclusion: In this cohort, adverse events were not very different from those seen in patients on either treatment alone and the combination of leflunomide plus infliximab did not appear to be as badly tolerated as described in a previous study.

Publication types

  • Clinical Trial

MeSH terms

  • Adjuvants, Immunologic / adverse effects*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Antinuclear / blood
  • Antibodies, Monoclonal / adverse effects*
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / physiopathology
  • Drug Therapy, Combination
  • Female
  • Humans
  • Infliximab
  • Isoxazoles / adverse effects*
  • Leflunomide
  • Male
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome
  • Withholding Treatment


  • Adjuvants, Immunologic
  • Antibodies, Antinuclear
  • Antibodies, Monoclonal
  • Antirheumatic Agents
  • Isoxazoles
  • Infliximab
  • Leflunomide