Management of breakthrough disease in patients with multiple sclerosis: when an increasing of Interferon beta dose should be effective?

BMC Neurol. 2011 Feb 25:11:26. doi: 10.1186/1471-2377-11-26.

Abstract

Background: In daily clinical setting, some patients affected by relapsing-remitting Multiple Sclerosis (RRMS) are switched from the low-dose to the high-dose Interferon beta (IFNB) in order to achieve a better control of the disease.

Purpose: In this observational, post-marketing study we reported the 2-year clinical outcomes of patients switched to the high-dose IFNB; we also evaluated whether different criteria adopted to switch patients had an influence on the clinical outcomes.

Methods: Patients affected by RRMS and switched from the low-dose to the high-dose IFNB due to the occurrence of relapses, or contrast-enhancing lesions (CELs) as detected by yearly scheduled MRI scans, were followed for two years. Expanded Disability Status Scale (EDSS) scores, as well as clinical relapses, were evaluated during the follow-up period.

Results: We identified 121 patients switched to the high-dose IFNB. One hundred patients increased the IFNB dose because of the occurrence of one or more relapses, and 21 because of the presence of one or more CELs, even in absence of clinical relapses. At the end of the 2-year follow-up, 72 (59.5%) patients had a relapse, and 51 (42.1%) reached a sustained progression on EDSS score. Overall, 85 (70.3%) patients showed some clinical disease activity (i.e. relapses or disability progression) after the switch. Relapse risk after increasing the IFNB dose was greater in patients who switched because of relapses than those switched only for MRI activity (HR: 5.55, p = 0.001). A high EDSS score (HR: 1.77, p < 0.001) and the combination of clinical and MRI activity at switch raised the risk of sustained disability progression after increasing the IFNB dose (HR: 2.14, p = 0.01).

Conclusion: In the majority of MS patients, switching from the low-dose to the high-dose IFNB did not reduce the risk of further relapses or increased disability in the 2-year follow period.Although we observed that patients who switched only on the basis on MRI activity (even in absence of clinical attacks) had a lower risk of further relapses, larger studies are warranted before to recommend a switch algorithm based on MRI findings.

MeSH terms

  • Adult
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / therapeutic use*
  • Interferon-beta / administration & dosage*
  • Interferon-beta / therapeutic use
  • Magnetic Resonance Imaging
  • Male
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / prevention & control*
  • Product Surveillance, Postmarketing / methods
  • Secondary Prevention
  • Severity of Illness Index

Substances

  • Immunologic Factors
  • Interferon-beta