Preventing long-term disability in CIDP: the role of timely diagnosis and treatment monitoring in a multicenter CIDP cohort

Abstract

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory disease affecting the peripheral nerves and the most frequent autoimmune polyneuropathy. Given the lack of established biomarkers or risk factors for the development of CIDP and patients' treatment response, this research effort seeks to identify potential clinical factors that may influence disease progression and overall treatment efficacy.

Methods: In this multicenter, retrospective analysis, we have screened 197 CIDP patients who presented to the University Hospitals in Düsseldorf, Berlin, Cologne, Essen, Magdeburg and Munich between 2018 and 2022. We utilized the respective hospital information system and examined baseline data with clinical examination, medical letters, laboratory results, antibody status, nerve conduction studies, imaging and biopsy findings. Aside from clinical baseline data, we analyzed treatment outcomes using the Standard of Care (SOC) definition, as well as a comparison of an early (within the first 12 months after manifestation) versus late (more than 12 months after manifestation) onset of therapy.

Results: In terms of treatment, most patients received intravenous immunoglobulin (56%) or prednisolone (39%) as their first therapy. Patients who started their initial treatment later experienced a worsening disease course, as reflected by a significant deterioration in their Inflammatory Neuropathy Cause and Treatment (INCAT) leg disability score. SOC-refractory patients had worse clinical outcomes than SOC-responders. Associated factors for SOC-refractory status included the presence of fatigue as a symptom and alcohol dependence.

Conclusion: Timely diagnosis, prompt initiation of treatment and careful monitoring of treatment response are essential for the prevention of long-term disability in CIDP and suggest a "hit hard and early" treatment paradigm.

Keywords: Autoimmune; CIDP; Neuroimmunology; Therapy.

Fig. 1

PRISMA flow chart illustrating screening and inclusion of patient records used in this study

Fig. 2

Clinical symptoms and disease course of typical CIDP versus CIDP variants. A, B Clinical symptoms and MRC scores on initial admission are depicted. Symptoms are displayed as relative percentage of all patients. C, D INCAT scores were determined at initial diagnosis (0), after 12, 24 and 36 months. Mean scores ± SEM are shown. Data was available from (typical CIDP/CIDP variants) 180/43 (diagnosis), 151/35 (after 12 months), 121/29 (after 24 months) and 110/27 (after 36 months) patients. A p-value ≥ 0.05 was classified as not significant, p < 0.05 (*) as significant, p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****) as highly significant. CIDP chronic inflammatory demyelinating polyneuropathy, INCAT inflammatory neuropathy cause and treatment, MRC Medical Research Council, SEM standard error of the mean

Fig. 3

First to fifth therapy of typical CIDP patients. Alluvial plot that shows the individual therapies of CIDP patients, chronologically from first to fifth. In this context, none means no change of therapy. CIDP chronic inflammatory demyelinating polyneuropathy

Fig. 4

Details on first treatment regimen of typical CIDP patients. A First treatment regimen of all patients in % (n = 187). The absolute values are indicated next to their corresponding relative percentages. B Patients’ response to their first therapies according to the SOC criteria are illustrated. C Fractions of the respective treatment regimens in absolute values of all SOC-responder patients (n = 110). D Distribution of the respective treatment regimens in absolute values of all SOC-refractory patients (n = 76). CIDP chronic inflammatory demyelinating polyneuropathy, SOC standard of care

Fig. 5

Comparison of early versus late onset of therapy in typical CIDP patients. A The start of the first therapy after first symptom manifestation is depicted in months: early onset of therapy was defined as start of first therapy up to 12 months after first manifestation of symptoms. Late start of therapy was set as start of first therapy more than 12 months after first manifestation of symptoms. B, C Mean INCAT arm and leg disability scores ± SEM at diagnosis (0), after 12, 24 and 36 months, respectively. Data was available from (early/late start of therapy) 85/80 (at diagnosis), 60/73 (after 12 months), 49/64 (after 24 months) and 43/59 (after 36 months) patients. A p-value ≥ 0.05 was classified as not significant, p < 0.05 (*) as significant, p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****) as highly significant. For a better clarity, not all significant results are shown. CIDP chronic inflammatory demyelinating polyneuropathy, INCAT inflammatory neuropathy cause and treatment, SEM standard error of the mean

Fig. 6

Comparison of treatment strategies, scores, and associated factors of SOC-responder versus SOC-refractory patients in typical CIDP patients. A, B Mean INCAT arm and leg disability scores ± SEM at diagnosis (0 months), after 12, 24 and 36 months, respectively. Data was available from (SOC-responder/SOC-refractory) 102/67 (at diagnosis), 86/58 (after 12 months), 68/47 (after 24 months) and 65/40 (after 36 months) patients. C Mean MRC sum scores ± SEM at diagnosis (0 months), after 12, 24 and 36 months, respectively. Data was available from (SOC-responder/SOC-refractory) 108/74 (at diagnosis), 48/48 (after 12 months), 37/37 (after 24 months) and 35/34 (after 36 months) patients. D Associated factors for a SOC-refractory status. Values are presented as Odds ratios with a 95% confidence interval. A p-value ≥ 0.05 was classified as not significant, p < 0.05 (*) as significant, p < 0.01 (**), p < 0.001 (***), and p < 0.0001 (****) as highly significant. For a better clarity, not all significant results are indicated. CIDP chronic inflammatory demyelinating polyneuropathy, INCAT inflammatory neuropathy cause and treatment, MRC Medical Research Council, SEM standard error of the mean, SOC standard of care

Fig. 7

Overview and clinical scores of sustained SOC-responders and transitioned SOC-refractory patients in typical CIDP patients. A The total amount of patients with the status sustained SOC-responder (patients who still met the SOC-responder status at 12 months follow-up) and sustained SOC-refractory (patients who transitioned to a SOC-refractory status at 12 months follow-up) after 12 months, respectively. B Mean MRC sum scores ± SEM of these patient subgroups after 12, 24 and 36 months, respectively. Data was available from (sustained SOC-responder/transitioned SOC-refractory) 29/15 (at diagnosis), 24/13 (after 12 months), 22/12 (after 24 months) and 20/10 (after 36 months) patients. C, D Mean INCAT arm and leg disability scores ± SEM of the depicted treatment-response cohorts after 12, 24 and 36 months, respectively. Data was available from (sustained SOC-responder/transitioned SOC-refractory) 30/15 (at diagnosis), 27/14 (after 12 months), 23/13 (after 24 months) and 23/11 (after 36 months) patients. CIDP chronic inflammatory demyelinating polyneuropathy, INCAT inflammatory neuropathy cause and treatment, MRC Medical Research Council, SEM standard error of the mean, SOC standard of care