Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports he is a consultant for Merck Sharp & Dohme Corp.
SYNOPSIS: Rituximab has been used “off label” for the treatment of primary chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with variable reports of success. These authors reported a high rate of response in patients who developed CIDP in the setting of other systemic immune-mediated disorders.
SOURCE: Roux T, Debs R, Maisonobe T, et al. Rituximab in chronic inflammatory demyelinating polyradiculoneuropathy with associated diseases. J Peripher Nerv Syst 2018;23:235-240.
Intravenous immune globulin (IVIG), plasma exchange (PLEX), and glucocorticoids are the pillars of treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), but each has its advantages and disadvantages. IVIG may lead to improvement more rapidly than steroids but it is expensive, sometimes limited in supply, and is less likely to result in remission, with a response rate of 40-60%. PLEX also may lead to more rapid improvement than steroids and has a response rate of up to 80%, but it is invasive, expensive, not as widely available, and venous access may be problematic. Steroids are inexpensive and readily available, but are fraught with significant side effects and have a response rate of 54-63%. Rituximab has been suggested as an alternative to prednisone as an immune modulator for treatment of CIDP.
This was a retrospective study of all CIDP patients in the database of Pitié-Salpêtrière Hospital, Paris, treated with rituximab between January 2004 and December 2016. Patients with anti-MAG antibodies were excluded. All received standard treatment (corticosteroids, IVIG, PLEX) for CIDP but additionally received rituximab, either because they had an insufficient response to or continued dependence on first-line CIDP treatment, or had an associated autoimmune or hematological condition requiring rituximab. Rituximab 375 mg/m2 usually was administered twice, two weeks apart (n = 11), with two patients receiving it weekly for four weeks, and nine patients receiving it monthly for four or six months. One lupus patient received it every three months for three years. Patients were seen in follow-up every four to eight weeks, and response to rituximab was defined as a five-point increase in the Medical Research Council (MRC) sum score, a one-point decrease in the Overall Neuropathy Limitations Scale (ONLS) score, discontinuation of first-line treatment(s), or an increase of at least one week in the interval between courses of IVIG or PLEX compared to the dependence threshold. Response was considered significant if it was maintained for at least two consecutive visits. Additionally, electrodiagnostic (EDX) studies were performed prior to and between five and nine months following the first rituximab infusion, with improvement defined as disappearance of conduction block in at least one site or two nerves showing decreased distal motor latency, improved motor conduction velocity by at least 10 m/s, or improved motor amplitude, with no nerve showing worsening. Worsening EDX was defined as at least one new site of conduction block or two nerves showing increased distal motor latency, slowed motor conduction velocity by at least 10 m/s, or decreased motor amplitude. Statistical analysis comprised Student’s t test, χ2 test, and the Shapiro-Wilk test, with significance set at P < 0.05.
Twenty-eight CIDP patients (12 men and 16 women) with a mean age of 66 years received rituximab. Eighteen patients had the common form of CIDP, seven had sensory CIDP, and three had Lewis-Sumner syndrome (multifocal acquired demyelinating sensory and motor neuropathy, MADSAM). All but one had an associated disease, either B-cell malignancy (n = 13), monoclonal gammopathy of undetermined significance (MGS, n = 7), or an autoimmune process, including rheumatoid arthritis or lupus (n = 1 each), anti-neurofascin 155 antibodies (n = 3), or anti-SSA/anti-SSB antibodies (n = 2). Thirteen (46%) received rituximab because of an insufficient response to CIDP first-line treatment, eight (29%) because of treatment dependence, and seven (25%) for hematological disease. Overall, within a median of six months, 21 patients (75%) responded to rituximab, with 11 demonstrating improved clinical scores, 10 decreasing their dependence threshold, and seven of the latter improving both. Of these 10, six were able to discontinue their first-line treatment, and four increased their inter-treatment interval by a median of three weeks (one to six weeks). Typical CIDP responded best (83%) vs. 43% of sensory CIDP and 67% of Lewis-Sumner disease, a statistically significant difference. Rituximab resulted in no major adverse events and appeared to improve clinical response and decrease dependence on first-line agents in CIDP patients with associated hematological or autoimmune disease.
Patients with CIDP represent a significant clinical and economic burden. Neuropathic pain, back pain, and osteoarthritis requiring opioids, antidepressants, and anticonvulsants are more frequent, as are hospitalizations, physician office visits, and outpatient prescriptions. Mean total costs increase by a factor of six, with therapy accounting for more than 50% of mean total costs.1 Additions to the therapeutic armamentarium against CIDP, including rituximab, are to be welcomed.
- Divino V, Mallick R, DeKoven M, Krishnarajah G. The economic burden of CIDP in the United States: A case-control study. PLoS One 2018;13:e0206205. doi.org/10.1371/journal.pone.0206205.