HIGH DISCONTINUATION RATE OF TREATMENT WITH LEFLUNOMIDE IN DAILY PRACTICE.

October 7, 2002

Philomine A van Pelt, Dirkjan van Schaardenburg, Irene EM Bultink, Ben AC

Dijkmans Amsterdam, Netherlands

BACKGROUND: Clinical studies of leflunomide in patients with rheumatoid

arthritis (RA) have shown rates of efficacy and adverse events that were

comparable to those of methotrexate and sulfasalazine (Smolen et al, Lancet

1999; Emery et al, Rheumatol 2000). However, such data may differ

substantially from what is encountered in daily practice. Therefore, we have

evaluated the discontinuation of leflunomide in clinical practice.

METHODS: Leflunomide was prescribed and monitored according to the

manufacturer¹s recommendations. We checked the medical records of all RA

patients who started with leflunomide in the period between 1 February 2000

and 1 May 2001.

RESULTS: 99 patients were included; 76% female, median age 57 years (range

27-82), median disease duration 9 years (0-53), median number of previously

used DMARD 4 (0-8). Comedication was used in 53 patients: prednisone (n=42),

methotrexate (n=9), sulfasalazine (n=1) and injectable gold (n=1).

Leflunomide was discontinued in 61 patients (62%), after a median of 12

weeks (range 1-64 weeks). The main reasons for discontinuation were: failure

(n=25, 41%), gastrointestinal symptoms (n=23, 38%), liver enzyme elevation

more than twice the upper limit of normal (n=5, 8%), neurological symptoms

(n=9, 15%), skin symptoms (n=9, 15%), hypertension (n=5, 8%) and leucopenia

(n=3, 5%). There were no statistically significant differences in: age at

the start of leflunomide, disease duration, number of previously used

DMARD¹s, and erythrocyte sedimentation rate, between the patient groups who

stopped and who continued leflunomide. There were no hospitalizations or

deaths due to adverse events. In total, 54 patients (55%) discontinued

leflunomide because of side effects; in the abovementioned clinical trials

this figure was 15-22%. 38 patients were still using leflunomide (median

duration of use 58 weeks, range 9-68) at the time of the survey.

CONCLUSION: The rate of discontinuation of leflunomide was unexpectedly

high. At least in part, this may be due to the selection of patients with

longstanding disease responding poorly to previous drugs.

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