Enhanced benefit of increasing interferon beta-1a dose and frequency in relapsing multiple sclerosis - The EVIDENCE study
ABSTRACT The EVIDENCE (Evidence of Interferon Dose-Response: European North American Comparative Efficacy) Study demonstrated that patients with multiple sclerosis (MS) who initiate interferon beta-1a therapy with 44 microg 3 times weekly (TIW) were less likely to have a relapse or activity on magnetic resonance imaging (MRI) compared with those who initiate therapy at a dosage of 30 microg 1 time weekly (QW).
To determine the effect of changing the dosage from 30 microg QW to 44 microg TIW in this extension of the EVIDENCE Study.
Patients with relapsing MS originally randomized to interferon beta-1a, 30 microg QW, during the comparative phase of the study changed to 44 microg TIW, whereas patients originally randomized to 44 microg TIW continued that regimen. Patients were followed up, on average, for an additional 32 weeks.
The within-patient pretransition to post-transition change in relapse rate.
At the transition visit, 223 (73%) of 306 patients receiving 30 microg QW converted to 44 microg TIW, and 272 (91%) of 299 receiving 44-microg TIW continued the same therapy. The post-transition annualized relapse rate decreased from 0.64 to 0.32 for patients increasing the dose (P<.001) and from 0.46 to 0.34 for patients continuing 44-microg TIW (P = .03). The change was greater in those increasing dose and frequency (P = .047). Patients converting to the 44-mug TIW regimen had fewer active lesions on T2-weighted MRI compared with before the transition (P = .02), whereas those continuing the 44-microg TIW regimen had no significant change in T2 active lesions. Patients who converted to high-dose/high-frequency interferon beta-1a therapy had increased rates of adverse events and treatment terminations consistent with the initiation of high-dose subcutaneous interferon therapy.
Patients receiving interferon beta-1a improved on clinical and MRI disease measures when they changed from 30 microg QW to 44 microg TIW.
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ABSTRACT: Objective: To explore the effects of exposure to subcutaneous (sc) interferon (IFN) beta-1a on efficacy in patients with relapsing-remitting multiple sclerosis (RRMS) enrolled in the PRISMS (Prevention of Relapses and disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) study.Methods: Patients with RRMS received IFN beta-1a, 44 or 22 µg sc three times weekly (tiw), or placebo, for 2 years, at which point placebo recipients were re-randomized to IFN beta-1a, 44 or 22 µg sc tiw, for a further 2-4 years. Long-term follow-up visits occurred 7-8 years after enrolment and allowed participation of patients who had previously discontinued treatment. Post hoc descriptive analyses were conducted within the lower (MIN) and upper (MAX) quartiles of patients divided according to cumulative dose of IFN beta-1a and cumulative time on treatment. Outcomes were explored in patients initially randomized to IFN beta-1a, 44 µg sc tiw, who had received continuous or noncontinuous therapy during the study.Results: For both cumulative dose and time analyses, the MIN and MAX groups comprised 96 and 95 patients, respectively. The continuous and noncontinuous groups included 45 and 91 patients, respectively. The MAX DOSE and MAX TIME groups had lower annualized relapse rates, lower rates of conversion to secondary progressive MS, lower percentages of patients with Expanded Disability Status Scale progression, higher percentages of relapse-free patients, and less T2 burden of disease than the MIN groups. The continuous therapy group had a lower annualized relapse rate and lower percentages of patients with Expanded Disability Status Scale progression or conversion to secondary progressive MS than the noncontinuous therapy group.Conclusions: The findings of these post hoc analyses suggest that high exposure to sc IFN beta-1a may be associated with better clinical outcomes than low exposure, and also highlight the importance of maximizing adherence. Additional prospective investigation is warranted to evaluate further the effects of treatment exposure on outcomes and to determine the benefits of interventions to improve adherence.Therapeutic Advances in Neurological Disorders 01/2011; 4(1):3-14. DOI:10.1177/1756285610391693
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ABSTRACT: Multiple sclerosis (MS) is a chronic, disabling, and progressive illness, representing one of the most common causes of neurological disability in young and middle-aged adults. There is not a definitive treatment for MS yet. However, disease-modifying drugs (DMDs) for MS, which include interferon-beta and copolymer-1 have shown to be effective in reducing the frequency and severity of relapses and the progression of disability. The clinical efficacy of such therapies has been well documented in the medical literature. Instead, the factors underlying the decision to start the pharmacological treatment, to continue it or to drop out, have not been studied so far. Adverse drug effects, as well as patients’ emotional states, therapeutic expectations, the need to assume the medicines very often, and lack of communication with medical staff, are some of the elements affecting patients’ adherence to the therapy. Data from medical records of 567 MS patients referred to the MS Centre of the IRCCS Centro Studi Neurolesi (Messina) between the years 2001-2008 have been retrospectively analyzed in a first phase. Factors influencing patient decision to start a pharmacological treatment with DMDs, in agreement with the neurologist suggestion, have been evaluated by applying a multinomial logit model. The second phase of the study was cross-sectional and analyzed the data obtained through a questionnaire administered to consecutive outpatients referred to Centro Studi Neurolesi within March and May 2009 (n = 143). The probability to proceed in the treatment or to drop out was estimated through a probit model. The present research constitutes a novelty among the existing economic and medical literature: in fact, there are no, so far, studies evaluating factors underlying MS patients’ decision to undergo a pharmacological treatment and to proceed it according to medical protocols. Moreover, a significant expenditure for health care systems is associated to MS treatment, both for patients who undergo the treatment (cost of medicines, productivity losses for patients who experience severe side effects, etc.) and for those who do not take the medicine or take it discontinuously. Given the documented evidence of augmenting costs (direct and indirect) with increasing disease severity, the ability of the DMDs to reduce relapse rates and slow the progression of MS may help to offset the cost of these therapies. Conversely, delayed treatment or poor compliance can dramatically increase costs and reduce benefits.