Definitions of the levels of the recommendations (A, B, C, U) and classification of the evidence (Class I-IV) are provided at the end of the "Major Recommendations" field.
- Based on conflicting primary outcome measures, IV immunoglobulin (IVIg) benefit is uncertain in children with Guillain-Barré syndrome (GBS).
- Based on 2 Class I studies, IVIg is as efficacious as plasmapheresis for treating GBS in adults. Because plasmapheresis is established as effective GBS treatment, the guideline committee concluded that IVIg also has established effectiveness.
- Based on one adequately powered Class I study, the combination of plasmapheresis and IVIg is probably not better than either treatment alone.
- Based on one underpowered Class I study, evidence is insufficient to support or exclude a benefit of adding methylprednisolone (MP) to IVIg in GBS.
- Data are insufficient to make a recommendation on optimal IVIg dosing.
There is insufficient evidence to support or refute the effectiveness of IVIg in children with GBS (Level U).
IVIg should be offered to treat GBS in adults (Level A).
IVIg combined with plasmapheresis should not be considered for treating GBS (Level B).
Evidence is insufficient to recommend MP in combination with IVIg (Level U).
Many experts consider it reasonable treatment to use IVIg for GBS in children given its effectiveness in the same disease in adults.
Chronic Inflammatory Demyelinating Polyneuropathy
- Based on 2 Class I studies, IVIg is effective for the long-term treatment of chronic inflammatory demyelinating polyneuropathy (CIDP).
- Data are insufficient to address the comparative efficacy of prednisolone and IVIg in treating CIDP.
IVIg should be offered for the long-term treatment of CIDP (Level A).
Dosing, frequency, and duration of IVIg for CIDP may vary depending on the clinical assessment. Data are insufficient to address the comparative efficacy of other CIDP treatments (e.g., steroids, plasmapheresis, immunosuppressants). Experts have identified that there may be overuse of IVIg in long-term care of CIDP. The guideline committee was unable to evaluate this question using available randomized trial data.
- Based on one Class I study, IVIg is probably effective in treating patients with myasthenia gravis (MG).
- Evidence is insufficient to compare the efficacy of IVIg and plasmapheresis in treating MG.
IVIg should be considered in the treatment of MG (Level B).
This recommendation was based on studies involving primarily moderately or severely affected patients. The benefits and risks of this medication should be weighed carefully in patients with mild MG. Further studies of IVIg efficacy in MG are warranted due to the few randomized trials and small study size to date.
Multifocal Motor Neuropathy
Based on consistent results from 3 Class II studies, IVIg is probably effective for multifocal motor neuropathy (MMN) treatment.
IVIg should be considered for the treatment of MMN (Level B).
MMN is a chronic disease requiring ongoing treatment. No data are available to address optimal treatment dosing, interval, and duration.
Neuropathy Associated with IgM Paraprotein
Based on 1 Class I study and 1 Class II study, IVIg is possibly ineffective for the treatment of IgM paraprotein–associated neuropathy. A modest benefit cannot be excluded due to each study's small sample size.
Evidence is insufficient to assess the role of IVIg in treating neuropathy associated with IgM paraprotein (Level U).
Based on 1 Class II study, IVIg is possibly effective for the treatment of nonresponsive dermatomyositis in adults.
IVIg may be considered for the treatment of nonresponsive dermatomyositis in adults (Level C).
Inclusion Body Myositis
Two Class I studies and 1 Class II study failed to demonstrate a consistent or significant clinical benefit of IVIg in treating inclusion body myositis (IBM).
Evidence is insufficient to support or refute the use of IVIg in treating IBM (Level U).
There is presently no effective treatment for IBM.
One Class I study showed a significant difference, but the difference was not clinically important for IVIg use on the most affected muscle in postpolio syndrome. One underpowered Class I study showed an effect of IVIg for pain in postpolio syndrome but no effect on strength or fatigue.
Evidence is insufficient to support or refute IVIg use in the routine treatment of postpolio syndrome (Level U).
There is presently no effective treatment for postpolio syndrome.
Lambert-Eaton Myasthenic Syndrome
Based on 1 Class II study, IVIg is possibly effective in Lambert-Eaton myasthenic syndrome (LEMS).
IVIg may be considered in the treatment of LEMS (Level C).
Classification of Recommendations
Level A = Established as effective, ineffective or harmful (or established as useful/predictive or not useful/predictive) for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies.)*
Level B = Probably effective, ineffective or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified population. (Level B rating requires at least one Class I study or two consistent Class II studies.)
Level C = Possibly effective, ineffective or harmful (or possibly useful/predictive or not useful/predictive) for the given condition in the specified population. (Level C rating requires at least one Class II study or two consistent Class III studies.)
Level U = Data inadequate or conflicting; given current knowledge, treatment (test, predictor) is unproven.
*In exceptional cases, one convincing Class I study may suffice for an "A" recommendation if 1) all criteria are met, 2) the magnitude of effect is large (relative rate improved outcome >5 and the lower limit of the confidence interval is >2).
Classification of Evidence for Rating of a Therapeutic Article
Class I = A randomized, controlled clinical trial of the intervention of interest with masked or objective outcome assessment, in a representative population. Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences. The following are also required:
- Concealed allocation
- Primary outcome(s) clearly defined
- Exclusion/inclusion criteria clearly defined
- Adequate accounting for drop-outs (with at least 80% of enrolled subjects completing the study) and cross-overs with numbers sufficiently low to have minimal potential for bias
- For non-inferiority or equivalence trials claiming to prove efficacy for one or both drugs, the following are also required*:
- The authors explicitly state the clinically meaningful difference to be excluded by defining the threshold for equivalence or non-inferiority.
- The standard treatment used in the study is substantially similar to that used in previous studies establishing efficacy of the standard treatment (e.g., for a drug, the mode of administration, dose and dosage adjustments are similar to those previously shown to be effective).
- The inclusion and exclusion criteria for patient selection and the outcomes of patients on the standard treatment are comparable to those of previous studies establishing efficacy of the standard treatment.
- The interpretation of the results of the study is based upon a per protocol analysis that takes into account dropouts or crossovers.
Class II = A randomized controlled clinical trial of the intervention of interest in a representative population with masked or objective outcome assessment that lacks one criteria a–e above or a prospective matched cohort study with masked or objective outcome assessment in a representative population that meets b–e above. Relevant baseline characteristics are presented and substantially equivalent among treatment groups or there is appropriate statistical adjustment for differences.
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 = Studies not meeting Class I, II, or III criteria including consensus or expert opinion.
*Note that numbers 1-3 in Class Ie are required for Class II in equivalence trials. If any one of the three is missing, the class is automatically downgraded to Class III.
**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).