To the Editor:

Bramanti et al. report enhanced spasticity in primary progressive MS (PPMS) patients treated with interferon β-1b (IFNβ-1b).1 Thirteen of 19 patients (68%) treated with IFNβ-1b manifested a significant increase in spasticity and 7 (37%) decided to discontinue treatment within 6 months after initiation of therapy.1 In the phase III trial of IFNβ-1b in secondary progressive MS, 37.8% of the patients in the verum group reported increased spasticity and 12.5% stopped treatment because of side effects.2 Unfortunately, it remained unclear how often increased spasticity caused treatment discontinuation.

We retrospectively analyzed our experiences with IFNβ-1b in relapsing-remitting MS (RRMS) to determine reasons for treatment discontinuation. Between January 1995 and November 1998, 90 patients with RRMS started treatment with open label IFNβ-1b in our MS outpatient clinic. The mean age was 34.9 ± 6.9 years, the mean disease duration 5.2 ± 4.3 years, and the mean Expanded Disability Status Scale score (EDSS)3 3.4 ± 1.6. Sixty-one were fully ambulatory (EDSS < 4) at treatment initiation: 29 already had an advanced disability with a restriction of walking distance (EDSS ≥ 4).

Sixty patients are still treated with IFNβ-1b (mean treatment duration 31.3 ± 11.3 months); 30 patients (33%) discontinued treatment. Reasons for early discontinuation were treatment failure assessed by the treating physician in 5 (4.5%), intolerable flu-like symptoms in 4 (3.6%), and severe injection-site reactions in 8 (7.2%) patients, six of them with injection-site necrosis. One patient stopped treatment because of severe depression, another with Graves’ disease, and a third with epilepsy; each developed the symptoms after initiating treatment. Two patients had no medical reasons for discontinuation.

Eight patients (7.2% of all patients, 27.6% of the patients with an EDSS ≥ 4) discontinued treatment because of spasticity severely impairing their walking capacity. Spasticity of the legs occurred several hours after the injection and lasted for 1 or 2 days. These eight patients were characterized by a higher age (39.2 ± 7.3 years), a longer disease duration (10.4 ± 3.3 years), and a higher EDSS (5.0 ± 1.1) as compared to the entire treatment population. They had pretreatment spasticity of their legs and had already been put on antispastic medication. An attempt to adapt the dosage of the antispastic therapy to the patients’ needs before treatment discontinuation was not successful, and the former walking capacity was only resumed after stopping IFNβ-1b treatment.

Increased spasticity was not reported as a side effect in the phase III trial of IFNβ-1b in RRMS,4 and it was present in only 13% of the patients in another open label observation of RRMS.5 In contrast, our data show that muscle hypertonia is the most important reason for treatment discontinuation in those patients with a long-standing disease and already advanced disability. Therefore, we plead for a refined selection of patients for treatment with IFNβ-1b, excluding those with marked spasticity. This refinement would reduce costs, increase the treatment’s efficacy, and augment the drug’s reputation.