Therapeutic Trials: Meeting Review^©

Abstracts written for <http://www.multiplesclerosis.com> in 2002 and reprinted here with permission.

Betaseron® and Avonex® efficacy differences become more pronounced over time

A large body of both MRI and clinical data show that interferon (IFN) beta-1b (Betaseron®) reduces both disease activity and progression more effectively than IFN beta-1a (Avonex®). Researcher Luca Durelli, reports that the difference in efficacy becomes even more pronounced over time.* This latest evidence of superior Betaseron efficacy was shown in a 2-year investigation of 188 relapsing-remitting MS patients. At 24 months, 51% of patients in the Betaseron group were free of relapses compared to 36% in the Avonex group (p=0.036). MRI data showed that 55% of Betaseron patients were free of new T2 lesions compared with only 26% of those receiving Avonex (p=0.0003). Furthermore, the T2 disease burden decreased by 2.8% in the Betaseron group and increased by 11.7% in patients on Avonex. Dr. Durelli said these results underline: "…the importance of conducting long-term studies, the only ones which, in the context of a chronic disease, may provide clinically relevant results."

* The Independent Comparison of Interferon (INCOMIN) Trial
[S13.004/A86]

Can patients who are doing well on high-dose, frequently administered interferons be switched to lower dose therapy given less often? The answer is "no."

INCOMIN investigators also examined the possibility of switching patients who had their disease stabilized with Betaseron® to a lower-dose, less frequently administered interferon (Avonex®). Twenty-seven RRMS patients without clinical signs of disease activity for at least 3 years were randomly assigned to one of two groups: Group 1 patients were gradually switched from alternate-day Betaseron to once-weekly Avonex whereas Group 2 continued on Betaseron 3 times a week (30 µg; n=13 and 8 MIU; n=14 respectively).

The results, presented by Pierangelo Barbero, clearly showed that IFN beta dose reduction is not advisable, even after years of absence of clinical and MRI disease activity.* After one year, exacerbation rates (as well as the proportions of patients with exacerbations), EDSS worsening, or MRI activity were significantly higher in the patients switched to Avonex (p=0.05). The researchers conclude that IFN beta treatment is chronic and patients responding well to higher, more frequent-dose medication should remain on the successful regimen.

* The Independent Comparison of Interferon (INCOMIN) Trial
[S62.004/A493]

Higher and more frequent doses of interferons significantly improve outcome

24-week results show dosing schedule has major impact on outcome:
Results of the first head-to-head comparison of two versions of IFN beta-1a: Rebif® (44 mcg subcutaneously, given three times weekly) vs Avonex® (30 mcg intramuscularly, once a week) were reported by Mohammad K. Sharief. This large, multicenter, randomized trial (n=677) showed that the higher dose, more frequently administered agent, Rebif, had a significantly greater impact on outcome than Avonex.* Importantly, 75% of patients treated with Rebif remained relapse-free throughout the 24 week-week study compared to 63% in the Avonex group (p=0.001). In addition, Rebif patients needed significantly fewer courses of steroid therapy than those treated with Avonex. According to Dr Sharief: "These findings support the hypothesis that dosing schedule has a major impact on the efficacy of IFN beta-1a, and indicate that higher and more frequent doses of IFN beta-1a are beneficial in RRMS."

48-week results prove long-term durability of increased efficacy:
Hillel Panitch told the audience that efficacy differences between the two dosing schedules of IFN beta-1a persisted out to 48 weeks. The data from the EVIDENCE study extension prove the long-term durability of the 24-week findings -that significant clinical and MRI benefit are provided by giving higher and more frequent doses of interferons.

* European-North American Comparative Efficacy (EVIDENCE) study
[S13.005/A86; S13.006/A86,87]

Adding MITX to Immunotherapy appears to improve outcome in patients with aggressive disease

Preliminary results suggest that patients with aggressive forms of MS may benefit from the combined use of Betaseron and mitoxantrone (MITX). Ten patients with relapsing remitting (RR) or secondary progressive (SP) multiple sclerosis had MITX added to their Immunotherapy. Douglas Jeffrey, who reported the findings, said the addition was well tolerated and, importantly, the median number of new enhancing lesions decreased by 81% and relapse rates decreased by 74% from baseline. Further studies are underway.

[S23.004/A167]

MITX proves relatively safe over the long term

Mitoxantrone (MITX/Mitox), originally developed as an antineoplastic drug, was recently approved for patients with MS by the U.S. Food and Drug Administration. Investigators from 12 French MS centers monitored the safety in 302 RRMS, 351 SPMS and 143 PPMS patients from 1992 to 2001. Gilles Edan, who presented the findings, said that although continued pharmacovigilence is warranted, the new agent appears generally well tolerated. While 12 patients (1.8%) experienced asymptomatic reduction in left ventricle ejection fraction (LVEF), there was no evidence of clinical heart failure in any patients. Acute myelogenous leukemia was detected in one individual 22 months into the study and 6 patients developed infection associated with low neutrophil (<500) counts.

Addendum: The same group tested the potential benefit of using MITX as induction therapy, following by chronic immunotherapy, for people with worsening disease. They discovered that disease activity dropped dramatically with this innovative regimen. The number of patients was small, but the potential benefits of such treatment is exciting.

[S23.005/S A168; PO3.023/A187]

Well-known "miracle" drug also proves valuable in MS

In addition to all its other uses, aspirin also appears to reduce the severity of fatigue in patients with multiple sclerosis. Dean M. Wingerchuk and colleagues at the Mayo Clinic studied 30 ambulatory patients with significant MS-related fatigue. Fifteen patients were treated with 650 mg aspirin morning and noon and another 15 received placebo. Good or excellent improvement in fatigue levels was reported by 42% of patients taking aspirin compared to 11% on placebo (p=0.008). Modified Fatigue Impact Scale scores were also significantly reduced in patients receiving active drug (p=0.035). The group concluded that aspirin may reduce fatigue severity in MS. An immmunomodulatory mechanism is probably the source of this effect.

[S62.003/A492]