This is the current release of the guideline.

Definitions of the strength of the recommendations (A, B, C, U) and classification of the evidence (Class I through Class IV) are provided at the end of the "Major Recommendations" field.

1. Treatment of multiple sclerosis (MS) with interferon beta (IFN beta) (Avonex, Betaseron, or Rebif) is associated with the production of neutralizing antibodies (Nabs) to the IFN beta molecule (Level A).
2. It is probable that the presence of NAbs, especially in persistently high titers, is associated with a reduction in the radiographic and clinical effectiveness of IFN beta treatment (Level B).
3. It is probable that the rate of NAb production is less with IFN beta-1a treatment compared to IFN beta-1b treatment (Level B). However, because of the variability of the prevalence data, and because Nabs disappear in the majority of patients even with continued treatment (especially in those with low-titer NAbs), the magnitude and persistence of any difference in seroprevalence between these forms of IFN beta is difficult to determine.
4. It is probable that the seroprevalence of Nabs to IFN beta is affected by one or more of the following: its formulation, dose, route of administration, or frequency of administration (Level B). Regardless of the explanation, it seems clear that IFN beta-1a (as it is currently formulated for intramuscular injection) is less immunogenic than the current IFN beta preparations (either IFN beta-1a or IFN beta-1b) given multiple times per week subcutaneously (Level A). Because NAbs may disappear in many patients with continued therapy, the persistence of this difference is difficult to determine (Level B).
5. Although the finding of sustained high-titer NAbs (>100 to 200 NU/mL) has been associated with a reduction in the therapeutic effects of IFN beta on radiographic and clinical measures of multiple sclerosis disease activity, there is insufficient information on the utilization of NAb testing to provide specific recommendations regarding when to test, which test to use, how many tests are necessary, and which cutoff titer to apply (Level U).

Definitions:

Classification of Evidence for Therapeutic Intervention

Class I: Prospective, randomized, controlled clinical trial with masked outcome assessment, in a representative population. The following are required: a) primary outcome(s) clearly defined; b) exclusion/inclusion criteria clearly defined; c) adequate accounting for dropouts and crossovers with numbers sufficiently low to have minimal potential for bias; and d) relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences.

Class II: Prospective matched group cohort study in a representative population with masked outcome assessment that meets a–d above OR a randomized controlled trial in a representative population that lacks one criteria a–d.

Class III: All other controlled trials (including well-defined natural history controls or patients serving as own controls) in a representative population, where outcome is independently assessed, or independently derived by objective outcome measurement.*

Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion.

* Objective outcome measurement: an outcome measure that is unlikely to be affected by an observer's (patient, treating physician, investigator) expectation or bias (e.g., blood tests, administrative outcome data).

Classification of Recommendations

A = Established as effective, ineffective, or harmful for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies.)

B = Probably effective, ineffective, or harmful for the given condition in the specified population. (Level B rating requires at least one Class I study or at least two consistent Class II studies.)

C = Possibly effective, ineffective, or harmful for the given condition in the specified population. (Level C rating requires at least one Class II study or two consistent Class III studies.)

U = Data inadequate or conflicting; given current knowledge, treatment is unproven.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Not applicable: The guideline was not adapted from another source.

2007 Mar 27

American Academy of Neurology - Medical Specialty Society

American Academy of Neurology (AAN)

Therapeutics and Technology Assessment Subcommittee

Primary Authors: D.S. Goodin, MD; E.M. Frohman, MD, FAAN; B. Hurwitz, MD; P.W. O'Connor, MD; J.J. Oger, MD, FRCPC, FAAN; A.T. Reder, MD; and J.C. Stevens, MD, FAAN

Therapeutics and Technology Assessment Subcommittee Members: Janis Miyasaki, MD, FAAN (Co-Chair); Yuen T. So, MD, PhD (Co-Chair); Carmel Armon, MD, MHS, FAAN (ex-officio); Vinay Chaudhry, MD, FAAN; Richard M. Dubinsky, MD, MPH, FAAN; Douglas S. Goodin, MD (ex-officio, facilitator); Mark Hallett, MD, FAAN; Cynthia L. Harden, MD; Kenneth J. Mack, MD, PhD; Fenwick T. Nichols III, MD; Michael A. Sloan, MD, MS, FAAN; James C. Stevens, MD; Paul W. O'Connor, MD, FAAN

This is the current release of the guideline.

None available

This summary was completed by ECRI Institute on May 14, 2007.

This NGC summary is based on the original guideline, which is copyrighted by the American Academy of Neurology.