An approach to assessing immunoglobulin dependence in chronic inflammatory demyelinating inflammatory polyneuropathy

Abstract

Regular immunoglobulin treatment maintains strength and prevents disability in chronic inflammatory demyelinating polyneuropathy (CIDP). Discrimination between active disease, with optimum symptom control on treatment, and disease in remission not requiring treatment is essential for therapeutic decision-making and clinical trial design. To compare treatment cessation versus gradual dose reduction in assessment of disease activity (immunoglobulin dependence) in a cohort of stable CIDP patients on maintenance immunoglobulin treatment. An approach to restabilization of immunoglobulin-dependent individuals is also described. Retrospective review of IVIg cessation or gradual reduction in 33 patients with stable CIDP on maintenance IVIg. Demographic, clinical and treatment data were collected; clinical monitoring data were recorded prospectively as part of routine clinical practice. A total of 21/33 patients (62.6%) were immunoglobulin dependent, (gradual dose reduction:11, cessation:10). Mean change in Inflammatory Rasch-built Overall Disability Scale (I-RODS) (À15, standard deviation [SD] 16) and Medical Research Council Sum Score (MRC-SS) (À4, SD: 4) was clinically and statistically meaningful (>75% exceeded minimum clinically important differences). Mean time to deterioration was 5.0 (SD: 4.6) months, shorter in cessation group (3.5 months) than gradual reduction group (8.8 months). All patients were restabilized to previous baseline (M: 2.3, SD: 4.3 months), half within 1 week of retreatment. A total of 12 patients (37.4%) remained stable without treatment for ≥2 years (remission). A total of 50% were identified rapidly by cessation and 50% by gradual dose reduction requiring mean 4.8 (SD: 2.8) years follow-up and costing £113 623 per person Ig spend. No predictors of disease activity were identified. A treatment cessation trial with close clinical monitoring is an efficient, cost-effective and safe approach to assessing disease activity in CIDP.

Association of plasma neurofilament light chain with disease activity in chronic inflammatory demyelinating polyradiculoneuropathy

“…Clinical decline on treatment withdrawal or suspension is the current approach to differentiating CIDP patients with active disease requiring ongoing maintenance treatment from those in remission 11, 12 . Using this approach on 10 stable, treated CIDP patients, we identified four with active disease and six in remission.…”

“…Clinical decline on treatment withdrawal or suspension is the current approach to differentiating CIDP patients with active disease requiring ongoing maintenance treatment from those in remission. 11,12 Using this approach on 10 stable, treated CIDP patients, we identified four with active disease and six in remission. There were no demographic, disease, or treatment differences between those subsequently found to have active disease and those in remission once IVIg was withdrawn.…”

Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Current Therapeutic Approaches and Future Outlooks

“…24,29 It is debatable as to whether gradual weaning off immunoglobulins is preferable to abrupt interruption. Although the latter method has been advocated, 30 this may on occasion, in our experience, result in major, not always subsequently fully reversible decline, with physical and psychological consequences. A recent Dutch study demonstrated that IVIg treatment withdrawal, performed progressively in steps of 25% dose reductions per course, was safe with regard to effective subsequent re-stabilization in case of relapse, bringing support to gradual IVIg wean.…”

Efficacy, safety and tolerability of rozanolixizumab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a randomised, subject-blind, investigator-blind, placebo-controlled, phase 2a trial and open-label extension study

“…No validated biomarkers exist for CIDP disease activity and immunoglobulin dependency is hard to establish, making identification of patients with CIDP difficult, particularly those with immunoglobulin-dependent CIDP. [22][23][24] In CIDP01, CIDP relapse according to the combined assessments of iRODS, adjusted INCAT disability and maximum grip strength showed that patients receiving placebo exhibited relatively stable disease, with only 53% relapsing during the double-blind period, suggesting that many of them did not have Ig-treatment-dependent active disease. We investigated the characteristics of patients who did and did not relapse in a post hoc analysis but did not observe any clear differences between groups.…”