Early therapy initiation is crucial in chronic inflammatory demyelinating polyneuropathy: prospective multimodal data from the German INHIBIT registry

Abstract

Background: Diagnosing chronic inflammatory demyelinating polyneuropathy (CIDP) can be challenging, leading to delays in initiating therapy. As disability in CIDP is mainly dependent on axonal damage, the impact of delayed immunotherapy remains unclear. We multimodally investigated the clinical outcomes of patients with early CIDP regarding different treatment strategies and time points.

Methods: Patients with CIDP diagnosis within 1 year before study inclusion were systematically selected from the prospective Immune-mediated Neuropathies Biobank (INHIBIT) registry. Clinical and therapeutic data, and findings from nerve conduction study (NCS), and nerve and muscle ultrasound were correlated at inclusion and 12 months later. The patient outcomes were compared between immunotherapies. The effect of timing immunotherapy on clinical outcomes was determined using regression analysis.

Results: In total, 30 patients were included (time from diagnosis to inclusion 22 ± 19 weeks). Low amplitudes of compound muscle potential were significantly associated with pathological spontaneous activity (PSA, r = 0.467) and correlated with the Heckmatt scale (r_Sp = 0.391). All three parameters were significantly associated with higher overall disability sum scores (NCS score r_Sp = 0.581, PSA r = 0.385, Heckmatt scale r_Sp = 0.472). The delays in initiating therapy resulted in progression of axonal damage (r_Sp = 0.467) and disability (R² = 0.200). The combination of first-line therapies led to reduced disability progression (r = 0.773), while second-line therapies resulted in improved overall axonal damage (r = 0.467).

Conclusions: Axonal damage occurs early and is the main cause of clinical disabilities. Prompt initiation of therapy is crucial to prevent axonal damage and thereby disability progression. A comprehensive therapeutic approach, including a combination of first- or second-line therapies, may improve long-term outcomes.

Keywords: Axonal damage; CIDP; Muscle ultrasound; Therapy.

Fig. 1

a Correlation of overall axonal damage in NCS and ODSS at baseline. A significant positive correlation was observed between axonal damage in NCS and the ODSS score at baseline (r = 0.581, p < 0.001). NCS = Nerve Conduction Study, ODSS = Overall Disability Sum Score. b Correlation of overall axonal damage in NCS and I-RODS at baseline. A significant negative correlation was observed between axonal damage in NCS and the I-RODS score at baseline (r = −0.499, p = 0.005). NCS = Nerve Conduction Study, I-RODS = Inflammatory Rasch-Built Overall Disability Scale. c Correlation of overall axonal damage in NCS and Heckmatt score at baseline. A significant positive correlation was observed between axonal damage in NCS and the Heckmatt score at baseline (r = 0.391, p = 0.048). NCS = Nerve Conduction Study. d Correlation of Heckmatt score and ODSS at 12 mFU. A significant positive correlation was observed between the Heckmatt score and the ODSS score at the 12 mFU. (r = 0.472, p = 0.042). ODSS = Overall Disability Sum Score, 12mFU = 12-month follow-up. e Correlation of Heckmatt score and counted number of fasciculations per 30 s in muscle ultrasound at 12 mFU. A significant positive correlation was observed between the Heckmatt score and the number of fasciculations in ultrasound at the 12 mFU (r = 0.507, p = 0.027). 12mFU = 12-Month Follow-Up

Fig. 2

Long-term immunotherapy for all patients in the cohort: the inner circle represents the first-line therapies administered until baseline, with a distinction between those who also received second-line immunotherapy. The outer circle shows the second-line immunotherapy. The order of second-line therapies follows the corresponding first-line therapies. In the cohort, 14/30 (47%) received second-line therapy. First-line therapies included 9 patients who received long-term repetitive intravenous immunoglobulin (IVIG) alone and 6 patients who received long-term repetitive glucocorticosteroids (GCs) alone or in combination with other first-line therapies (IVIG, GCs, or plasma exchange [PE]). Second-line therapies included eight patients receiving rituximab, 4 patients receiving azathioprine, 1 patient receiving azathioprine + mycophenolate mofetil (MMF), and 1 patient receiving cyclosporine A. One patient received no therapy

Fig. 3

a Correlation of disease duration before therapy initiation in weeks and changes in overall axonal damage in NCS from baseline to 12mFU. The significant positive correlation (rSp = 0.467, p = 0.025) indicates that longer delays in therapy initiation are associated with reduced improvement in axonal damage. b Correlation of disease duration before therapy initiation in weeks and changes in I-RODS score from baseline to 12mFU. Early initiation of therapy is associated with a more significant improvement in I-RODS score (regression coefficient = −0.065 ± 0.028, R² = 0.200, p = 0.028). c Correlation of disease duration before therapy initiation in weeks and changes in MRC sum score from baseline to 12mFU. Early initiation of therapy is associated with a more significant increase in muscle strength (regression coefficient = −0.060 ± 0.026, R² = 0.242, p = 0.038)