By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
SYNOPSIS: First-line therapy for chronic inflammatory demyelinating polyneuropathy is intravenous immunoglobulin (IVIG), but the timing and method for withdrawal of this treatment are uncertain. In a retrospective review of stable patients on IVIG, investigators at the National Hospital in London observed that there was no significant difference in the likelihood of deterioration or response to retreatment if IVIG was stopped abruptly or tapered slowly.
SOURCE: Kapoor M, Compton L, Rossor A, et al. An approach to assessing immunoglobulin dependence in chronic inflammatory demyelinating inflammatory polyneuropathy. J Peripher Nerv Syst 2021;26:461-468.
Intravenous immunoglobulin (IVIG), which is easy to administer compared to plasma exchange and has a more rapid response compared to glucocorticoids, is effective treatment for chronic inflammatory demyelinating polyneuropathy (CIDP). Improvement within one month is significantly higher with IVIG compared to placebo (44% vs. 26%), the relapse rate is significantly lower (13% IVIG vs. 45% placebo), and IVIG provides a longer time until relapse.
Unfortunately, treatment with IVIG alone usually does not result in remission. Of the 75% of patients who will improve initially, 85% will require maintenance treatment, with only about 15% able to stop IVIG after two to three years. When a patient is doing well on maintenance IVIG, how may one best assess disease activity? In a stabilized patient, should IVIG be stopped abruptly or should gradual dose reduction be pursued?
Using European Federation of Neurological Societies/Peripheral Nervous System guidelines, investigators retrospectively identified all CIDP patients seen between 2008 and 2018 at the National Hospital of Neurology and Neurosurgery, London, in whom IVIG dependence was tested either by gradual dose reduction or immediate treatment cessation.
Data collected included disease duration, clinical and neurophysiological information, and IVIG maintenance regimen. Baseline and follow-up outcome measures were obtained in response to an IVIG dependence challenge, with IVIG restarted if IVIG dependence was determined. IVIG independence (remission) was defined as absence of deterioration for at least two years following discontinuation of IVIG, with patients evaluated at six- to 12-month intervals.
Outcome measures included the Inflammatory Rasch-built Overall Disability Scale (I-RODS) and the Medical Research Council sum score. Statistical analysis comprised Mann-Whitney U tests and Fisher’s exact tests, with two-tailed P values < 0.05 deemed significant.
Among 33 stable CIDP patients on IVIG maintenance therapy who underwent at least one IVIG dependence challenge between 2008 and 2018, 16 (48.4%) underwent treatment cessation and 17 (51.2%) underwent gradual dose reduction. When evaluating the entire group (33 patients), 21 (63.6%) were deemed to have active disease and were IVIG dependent, and 12 (36.4%) were in remission without the need for further IVIG, with similar proportions from each group.
Among the 21 patients with active disease, no significant difference was appreciated in the deterioration of scores between the two groups who had IVIG withdrawn, with a mean time of five months from baseline to nadir, longer for the gradual reduction group (8.8 months) compared to the cessation group (3.5 months). Time to deterioration was unrelated to IVIG dose or frequency of administration, and re-stabilization was achieved in all patients, more rapidly in the gradual reduction group compared to the cessation group, two weeks vs. 14.1 weeks, respectively.
Overall, one-half of the patients who deteriorated after IVIG withdrawal improved within one week of retreatment. No statistically significant factor was identified to discern which patients still proved to have active disease and which did not. IVIG cessation, with close clinical monitoring, is a safe and effective manner of determining which CIDP patients require continued maintenance therapy and which are in remission.
COMMENTARY
To what degree does demyelination vs. axonal degeneration play a role in the disability of CIDP? Among 95 patients with typical or variant CIDP who underwent electrophysiological studies in a single-center, prospective, observational, cohort study at St. Josef-Hospital, University Hospital Bochum, Germany, nerve conduction study (NCS) evidence of axonal loss strongly correlated with disability, both at initial diagnosis and during the course of active disease.
Upper limb distal compound muscle action potential amplitudes correlated best with overall clinical function. Axonal damage, as opposed to demyelination, is the main determinant of disability in CIDP and, although symptoms usually are more predominant in the legs, upper limb NCS is most predictive of disability.1
REFERENCE
- Gruter T, Motte J, Bulut Y, et al. Axonal damage determines clinical disability in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): A prospective cohort study of different CIDP subtypes and disease stages. Eur J Neurol 2021; Oct 22. doi: 10.1111/ene.15156. [Online ahead of print].
