Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports no financial relationships relevant to this field of study.
SYNOPSIS: In the United States, first-line treatment for chronic inflammatory demyelinating polyneuropathy (CIDP) is intravenous immunoglobulin (IVIG). Authors of this retrospective survey from Europe found that corticosteroid treatment had similar efficacy as IVIG and should be considered as first-line therapy for CIDP.
SOURCE: van Lieverloo GGA, Peric S, Doneddu PE, et al. Corticosteroids in chronic inflammatory demyelinating polyneuropathy: A retrospective, multicentre study, comparing efficacy and safety of daily prednisolone, pulsed dexamethasone, and pulsed intravenous methylprednisolone. J Neurol 2018;265:2052-2059.
Glucocorticoids, intravenous immunoglobulin (IVIG), and plasma exchange are the mainstays of therapy for chronic inflammatory demyelinating polyneuropathy (CIDP), with the initial choice among them decided by availability, disease severity, venous access, treatment side effects, cost, and concurrent illness. When disease is mild with minimal effect on quality of life or function, treatment may not even be necessary. If glucocorticoids are contraindicated, alternative immunosuppressant agents include azathioprine, cyclosporine, methotrexate, mycophenolate mofetil, rituximab, or tacrolimus. When corticosteroids are administered, various regimens may be offered. Which regimen is most effective and safe for CIDP?
Data on treatment-naïve CIDP patients were collected retrospectively from 2000 until 2018 from three centers in Europe, including Serbia, The Netherlands, and Italy, where corticosteroids were considered first-line treatment. All patients satisfied European Federation of Neurological Societies and Peripheral Nerve Society (EFNS/PNS) criteria for definite, probable, or possible CIDP, and were treated with either oral prednisone or prednisolone, 1-1.5 mg/kg/d for six weeks followed by a taper over at least eight months; oral dexamethasone 40 mg/d for four days, monthly for six months; or intravenous (IV) methylprednisolone, 500 mg/d for four days, with at least two further courses at 1-2 g/month, depending on disease severity. Any patient who did not improve on the regimen was given IVIG. The primary outcome was improvement in motor or sensory impairment as measured by the treating neurologist and/or Rankin scale, with no further need for treatment. Any patient who received IVIG was considered a nonresponder. The secondary outcome was the remission rate, defined as treatment-free stable or improving clinical status, with relapse defined as any setback requiring treatment. Statistical analysis comprised the Fisher-Freeman-Halton t test, one-way ANOVA, two-tailed t test, and Kruskal-Wallis tests, as applicable, with post hoc analyses also encompassing the Mann-Whitney U test. Statistical significance was defined as P < 0.05.
Among 196 screened patients, 125 received corticosteroids alone and were included in the study, of which 54% (n = 67) were treated with daily oral prednisone, 30% (n = 37) with oral dexamethasone, and 17% (n = 21) with IV methylprednisolone. Corticosteroid treatment resulted in a 60%
(n = 75) response rate overall, with no significant difference between the three treatment regimens. Fifty-seven percent improved with either oral prednisone or IV methylprednisolone, and 68% improved following oral dexamethasone. Among the 75 responders, 61% (n = 46) remained in remission over a median follow-up of 55 months. Of the 29 patients who relapsed, 69% (n = 20) did so within six months following treatment cessation. Corticosteroids resulted in a 33% probability of five-year remission, with severe adverse events occurring in two patients (severe hypertension and myocardial infarction in one each) and moderate adverse events in 8% (n = 10), including glaucoma, hypertension, de novo diabetes, depression, Cushingoid appearance, and gastrointestinal complaints. Corticosteroids resulted in an improvement in 60%, with remission in 61% of responders, and any modality of administration was equally efficacious and safe.
Recently described in patients with inflammatory neuropathies, IgG autoantibodies caspr and neurofascin-155 are associated with the subacute onset of severe motor weakness and poor response to IVIG, with the latter autoantibody additionally associated with debilitating tremor of cerebellar origin. Anti-neurofascin IgM autoantibodies have been reported in 8% of patients with inflammatory neuropathy but also in 5% with idiopathic neuropathy. In a recent report, IgM autoantibodies against neurofascin-155, in titers ranging from 1:100 to 1:400, were detected by ELISA in five patients, four with CIDP, three of whom also presented with tremor and one with Guillain-Barré syndrome. Electrodiagnostic studies were consistent with demyelinating neuropathy, although nerve biopsies showed axonal injury in three and demyelination only in one. IgM neurofascin-155 autoantibodies may be worth testing in patients with inflammatory neuropathies, but their pathogenic role remains to be determined.1
- Doppler K, Stengel H, Appeltshauser L, et al. Neurofascin-155 IgM autoantibodies in patients with inflammatory neuropathies. J Neurol Neurosurg Psychiatry 2018; Jun 26. doi:10.1136/jnnp-2018-318170. [Epub ahead of print].