Induction of Serological Lupus in Patients on Leflunomide and Infliximab

October 29, 2002

Category: 17 RA‹treatment

J Bingham, Anabela Barcelos, Maya H Buch, ,

Emery

University of Leeds, Leeds, United Kingdom

Presentation Number: 361

Poster Board Number: 361

Keywords: Rheumatoid Arthritis, Infliximab, Leflunomide

Aims and Objective: Leflunomide (LEF) is a relatively new DMARD licensed for

the treatment of RA. LEF has not previously been associated with an increase

in ANA titre or lupus-like side effects. Infliximab in combination with MTX

has been associated with an modest increase in dsDNA titres in the ATTRACT

study but there was only one case of clinical lupus out of 340 patients

treated. We are currently conducting an open label study of combination

therapy with LEF and infliximab and have noticed that a high proportion of

patients have become strongly ANA positive with a high dsDNA titre. We have

compared the increase of ANA titre in patients receiving this combination

therapy with a control group receiving LEF alone.

Methods: 40 patients with lack of effect (ACR 0) with at least 3 months of

leflunomide without toxicity were enrolled into an open study where

infliximab was added in combination. The ANA and dsDNA titres were measured

at baseline and then at 12 week intervals during the study. The dose of

infliximab was 3 mg/kg given at 0, 2, 6 and then 8-weekly. For the control

group we retrospectively identified 109 patients who had received LEF

monotherapy in our hospital. ANA titres were measured at baseline and at 12

and 24 weeks following commencing therapy. dsDNA titres were only measured

in those patients where the ANA titre rose above normal. Normal ranges for

our laboratory: ANA < / = 1/40, dsDNA <100 IU.

Results: The number of patients on combination therapy with a positive ANA

titre rose during the study (11% at week 0, 30% at week 12, 38% at week 24,

61% at week 36, 56% at week 48 and 100% at week 60) and the mean dsDNA titre

was over 100 by week 24. No clinical lupus was seen. There was a high

drop-out rate in this study due to adverse events, but there was no

relationship between discontinuation and increased ANA/dsDNA titres. In the

monotherapy group there was no significant rise in the number of patients

with a positive ANA (17% at baseline, 13% at 12 weeks and 17% at 24 weeks).

Conclusion: The combination of infliximab with LEF induces an increase in

ANA and dsDNA titres in all patients staying on therapy that was not seen in

patients on LEF alone. This suggests a specific effect on autoantibody

production.

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