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.
Acute Inflammatory Demyelinating Polyneuropathy (AIDP)/Guillain-Barré Syndrome (GBS)
On the basis of consistent findings from Class I studies, plasmapheresis is established as effective for the treatment of AIDP/GBS severe enough to impair the ability to walk independently or severe enough to require mechanical ventilation. For milder AIDP/GBS, in which ambulation is preserved, plasmapheresis is probably effective, based on a single Class I study.
Plasmapheresis should be offered in the treatment of AIDP/GBS severe enough to impair independent walking or to require mechanical ventilation (Level A). Plasmapheresis should be considered in the treatment of milder clinical presentations of AIDP/GBS (Level B).
Intravenous immunoglobulin (IVIg) is an alternative treatment used in patients with AIDP/GBS. There is insufficient evidence to demonstrate the superiority of one treatment over the other.
Chronic Inflammatory Demyelinating Neuropathy (CIDP)
Based on 2 Class I studies, plasmapheresis is established as effective in the short-term treatment of CIDP; both studies showed the beneficial effect is not sustained, with worsening beginning 1–5 weeks after last plasmapheresis treatment.
Plasmapheresis should be offered as a short-term treatment for patients with CIDP (Level A).
Steroids, IVIg, and immunosuppressants have also been used in the treatment of CIDP.
Plasmapheresis is probably effective in immunoglobulin A (IgA)- and immunoglobulin G (IgG)-monoclonal gammopathy of undetermined significance (MGUS)–associated polyneuropathy, based on one Class I study. On the basis of one Class I and one Class III study, plasmapheresis is probably not effective in polyneuropathy associated with immunoglobulin M (IgM) MGUS.
Plasmapheresis should be considered in polyneuropathy associated with IgA and IgG MGUS (Level B). Plasmapheresis should not be considered in the treatment of polyneuropathy associated with IgM MGUS (Level B).
Myasthenia Gravis (MG)
There are inadequate data to evaluate the use of plasmapheresis in the treatment of myasthenic crisis or in the treatment of MG prethymectomy.
Because of the lack of randomized controlled studies with masked outcomes, there is insufficient evidence to support or refute the efficacy of plasmapheresis in the treatment of myasthenic crisis (Level U) or MG prethymectomy (Level U).
Despite the fact that the use of plasmapheresis in myasthenic crisis and MG prethymectomy receives a Level U recommendation, plasmapheresis is used at many medical centers for these indications.
Central Nervous System (CNS) Demyelinating Disease
Plasmapheresis as adjunctive therapy is probably effective for management of exacerbations in relapsing forms of multiple sclerosis (MS), based on a single Class I study. Based on a single Class II study, plasmapheresis is possibly effective for acute fulminant CNS demyelinating diseases (including MS, acute disseminated encephalomyelitis, neuromyelitis optica, and transverse myelitis) that fail to respond to high-dose corticosteroid treatment. Because the study included subgroups of patients with demyelinating diseases, it is not possible to determine if plasmapheresis is more or less effective in patients with different demyelinating diseases. For chronic progressive or secondary progressive MS, plasmapheresis is established as ineffective based on consistent Class I evidence. (Note that the term chronic progressive MS is no longer used, but previously included patients are now described as having either primary progressive MS or secondary progressive MS.)
Plasmapheresis should be considered for the adjunctive treatment of exacerbations in relapsing forms of MS (Level B). Plasmapheresis may be considered in the treatment of fulminant CNS demyelinating diseases that fail to respond to high-dose corticosteroid treatment (Level C). Plasmapheresis should not be offered for chronic progressive or secondary progressive MS (Level A).
No studies on the efficacy of plasmapheresis compared to other treatment options in MS are available.
Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS)
There are inadequate data to determine the efficacy of plasmapheresis in the treatment of acute obsessive-compulsive disorder (OCD) and tic symptoms in the setting of PANDAS (one Class III study).
There is insufficient evidence to support or refute the use of plasmapheresis in the treatment of acute OCD and tic symptoms in the setting of PANDAS (Level U).
There are inadequate data to determine the efficacy of plasmapheresis in Sydenham chorea (one Class III study).
There is insufficient evidence to support or refute the use of plasmapheresis in the treatment of Sydenham chorea (Level U).
Classification of Recommendations
The strength of practice recommendations is linked directly to the level of evidence:
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 Therapeutic Intervention
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 crossovers 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 are 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).