Inflammatory Neuropathy Consortium base (INCbase): a protocol of a global prospective observational cohort study for the development of a prediction model for treatment response in chronic inflammatory demyelinating polyneuropathy

Abstract

Background: INCbase is an international, multicenter prospective observational study using a customizable web-based modular registry to study the clinical, biological and electrophysiological variation and boundaries of chronic inflammatory demyelinating polyneuropathy (CIDP). The primary objective of INCbase is to develop and validate a clinical prediction model for treatment response.

Methods: All patients meeting clinical criteria for CIDP can be included in INCbase. Collected data include demographics, clinical history, diagnostics and various domains of clinical outcomes. Data is collected at a minimum of every 6 months for two years, and more frequently at the discretion of the investigational site to allow for assessment of unexpected changes in treatment response or clinical status. Participants can be enrolled in various sub-studies designed to capture data relevant to specific groups of interest. Data is entered directly into the web-based data entry system by local investigators and/or participants. Collection and local storage of biomaterial is optional. To develop a clinical prediction model for treatment response, newly diagnosed patients with active disease warranting start of first-line treatment will be included. The study population will be split into a development and validation cohort. Univariate and multivariate logistic regression analysis will be used to identify and combine predictors at start of treatment for treatment response at six months. Model performance will be assessed through discrimination and calibration in an external validation cohort. The externally validated prediction model will be made available to researchers and clinicians on the INCbase website.

Discussion: With this study, we aim to create a clinically relevant and implementable prediction model for treatment response to first line treatments in CIDP. INCbase enrollment started in April 2021, with 29 centers across 8 countries and 303 patients participating to date. This collaborative effort between academia, patient advocacy organizations and pharmaceutical industry will deepen our understanding of how to diagnose and treat CIDP.

Keywords: Biomarkers; Chronic inflammatory demyelinating polyneuropathy; Clinimetrics; Diagnosis; Outcome; Prediction model; Prognosis; Treatment.

Fig. 1

Follow-up schedule and outcome parameters.Visits are planned at minimum every six months (core module), with additional visits for patients starting treatment or treatment withdrawal (extended module). The home-assessment model includes grip strength and patient reported outcomes every two weeks between visits. Additional unscheduled visits can be performed if necessary. INCAT-DS, Inflammatory Neuropathy Cause and Treatment Disability Score. CDAS, CIDP disease activity status. MRC-SS, Medical Research Council Sum Score. mISS, Modified Inflammatory Neuropathy Cause and Treatment Sensory Sum score. I-RODS, Inflammatory Rasch-Overall Disability Scale. EQ-5D, EuroQol quality of life. PGIC, Patient Global Impression of Change. R-FSS, Rasch-built Fatigue Severity Scale. AE, adverse events. PI-NRS, Pain Intensity Numeric Rating Scale. HADS, Hospital Anxiety and Depression Scale

Fig. 2

INCbase infrastructure

Fig. 3

INCbase patient enrolment and center participation

Fig. 4

Overview of INCbase participating countries and centers. Image created with mapchart.net