RESEARCH - Arava is as effective in combination with TNF-alpha antagonists as MTX, but has more side effects

[Guest guest]

ACR/ARHP 2008 Scientific Meeting

Session: RA Treatment Strategies and Treatment Safety

Tuesday, Oct 28, 2008, 9:00 AM - 6:00 PM

Presentation: 1655 - Leflunomide is as effective in Combination with

TNFα Antagonists as MTX, but has more Side Effects: Results from a

Case-Control-Study

Author(s): Jochen Wacker, e Lutz, Matthias Englbrecht, Bernhard

Manger, Georg Schett. Universitätsklinikum Erlangen, Department of

Rheumatology and Immunology, Erlangen, Germany

Abstract:

Background:

TNFα antagonists (TNF-A) are well established in RA Therapy after

failure of conventional DMARDs. Usually, the combination with MTX is

recommended. If MTX is not well tolerated, other DMARDs like

Leflunomide (LEF) are used effectively. There are several studies

showing the efficacy of a combination of LEF with TNF-A, but there are

no controlled trials comparing the outcome of the combination

MTX/TNF-A with LEF/TNF-A.

Objective:

We performed a retrospective Case-Control-Trial to evaluate efficacy

and safety of the combination therapy MTX/TNF-A compared to LEF/TNF-A.

Methods:

24 patients with a combination of LEF with any TNF-A (INF, ADA, ETA)

were searched from the database of our out-patient-clinic. All

patients had active disease under DMARD monotherapy (i.e., MTX or LEF)

before the TNF-A was added.

They were matched for DAS28 at the beginning of this combination

therapy to a control group of 24 patients on MTX/TNF-A. DAS28 was

analyzed at 3, 6, and 12 months after start. The primary endpoint was

a significant improvement in the DAS28 after 12 months without change

of therapy. Secondary endpoints were the reduction in DAS28 at 3, 6,

and 12 months, adverse events, and discontinuation or switch due to

lack or loss of efficacy or due to side effects.

Results:

There were no significant differences between both groups regarding

population characteristics (disease duration; number of previous

DMARDs; subjects with positive RF, positive CCP-antibodies, or with

erosive disease). 23/24 patients in the LEF group had previously

failed MTX.

In the LEF group, 12 patients (50.0%) reached the primary endpoint,

compared to 13 (54.1%) in the MTX group. In both groups, the average

DAS28 dropped significantly after 12 months from 6.0 (both groups) to

4.1 (LEF, p< 0.001) and 4.2 (MTX, p< 0.001), with no significant

difference between the two groups at each timepoint.

6 subjects (25.0%) discontinued the combination therapy in the LEF

group due to adverse events, compared to 2 (8.3%) in the MTX group,

while another 6 patients (25.0%) on LEF did not reach the primary

endpoint due to lack or loss of efficacy (MTX: 9 subjects). In the LEF

group, 16 patients experienced adverse events compared to 9 in the MTX

group (p<0.01). Most common AEs for LEF were diarrhea (n=4),

hypertension (n=4), and infections (n=3); the most frequent side

effect in the MTX group was nausea (n=3).

Conclusions:

The combination of LEF with TNF-A is comparable in efficacy to the

combination MTX/TNF-A. The patients in this study, however,

experienced significantly more AEs and more discontinuations due to

adverse events if treated with LEF.

http://www.abstractsonline.com/plan/start.aspx?mkey={5880E483-F47E-4EFF-A557-2EF\

143592815}

Not an MD