Evaluating the short-term and long-term therapeutic effects of immunoadsorption compared with plasma exchange in chronic inflammatory demyelinating polyneuropathy: a long-term, prospective, observational study

Abstract

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune-inflammatory disease of the peripheral nervous system. Corticosteroids, intravenous immunoglobulins (IVIGs), and plasma exchange (PLEX) constitute the main therapeutic options, but immunoadsorption (IA) represents a noteworthy alternative to PLEX due to its excellent tolerability and its capability to remove higher rates of autoimmune antibodies. However, evidence of its therapeutic value in CIDP is low, while the effect of repeated IA as long-term therapy is largely unknown. Therefore, in this study, we sought to evaluate the short- and long-term therapeutic effects of IA in CIDP compared to PLEX and preceding therapies (IVIGs and corticosteroids).

Methods: Between 02/12/2013 and 03/03/2025, we prospectively evaluated the course of disease of patients with CIDP who received at least one cycle of IA or PLEX via Shaldon catheter or arteriovenous shunt. All patients were treated in the Department of Neurology of Ulm University, Germany. All patients fulfilled the diagnostic criteria of typical CIDP according to the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guideline on diagnosis and treatment of CIDP, had a continuously progressive course of disease, and had previously received treatment with steroids, IVIGs, or both, with insufficient response. All eligible patients who gave their informed consent were selected for the study. Participant data were collected and retrieved using individual case report forms and medical records. One cycle of IA or PLEX consisted of 5 treatments on 5 consecutive days. As the primary outcome parameter, we used a combined CIDP score of 3 validated scales comprising disability (Inflammatory Neuropathy Cause and Treatment (INCAT) score), motor score (Medical Research Council, MRC), and vibration sensitivity (tuning fork test). For short-term effects, we compared absolute CIDP scores 3 days before and directly after the last treatment of each cycle; for long-term effects, we compared changes of CIDP score per month during IA or PLEX compared to preceding treatments in patients with an observation period of at least 6 continuous months under IA or PLEX. We systematically evaluated adverse events (AEs), and collected safety laboratory data as well as immunoglobulin (Ig) reduction levels.

Findings: In total, 80 patients were included, of which 74 received at least one cycle of IA, 25 received at least one cycle of PLEX, and 19 received at least one cycle of both IA and PLEX and were considered for both treatment groups for respective analyses. 41 IA patients and 16 PLEX patients received 2 or more cycles (median 4 (IQR 2-7.5), maximum 43 cycles) over a median time period of 12.0 (6.0-34.0) months in median time intervals of 2.5 (1.9-4.3) months. We observed improvements of CIDP scores post-treatment in the IA group (median improvement from 310 (224-374) to 321 (234-373) points; median difference 5.0 (95% CI 2.0-6.0), p < 0.0001), but not in the PLEX group (median 254 (214-358) vs. 254 (209-351); median difference 0.0 (95% CI 0.0-5.0, p = 0.12). Long-term progression rates compared to preceding corticosteroid and IVIG therapies decreased from 3.8 (2.2-9.1) to 0.2 (-0.5-2.2) points/month in the IA group (median difference -4.0 (95% CI -6.9 to -1.9), p < 0.0001), and from 4.2 (2.6-17.2) to -1.1 (-1.6-0.5) points/month in the PLEX group (median difference -6.3 (95% CI -19.9 to -1.9), p = 0.0010), corresponding to a clinical stabilization of disease progression. We detected 12 (5.0%) asymptomatic and 3 (1.3%) symptomatic thromboses of the jugular veins associated with Shaldon catheter placement among 240 cycles of IA, and 6 (7,5%) thromboses of the jugular vein (all asymptomatic) among 79 cycles in the PLEX group, representing the main complication for both procedures. In both groups, hypoproteinemia (IA 100%, PLEX 93.5%), thrombocytopenia (IA 33.6%, PLEX 4.9%), and anemia (IA 21.6%, PLEX 61.8%) were the most common laboratory findings during treatment.

Interpretation: Our results suggest that repeated IA and PLEX might constitute promising therapeutic options in patients with CIDP who do not sufficiently respond to corticosteroids and IVIGs, stabilizing the disease in the majority of patients. However, its invasive nature and significant risk of jugular vein thromboses must be considered. Study limitations include non-randomised group allocation, retrospective collection of data related to preceding treatments, the possibility of sub-optimal treatment pre-baseline, the limited number of patients, and potential interfering elements (such as cross-overs between IA and PLEX) caused by the long observation time. Because of these limitations, study results do not allow a direct comparison of effectiveness between IA and PLEX, and further randomised controlled trials are needed in this regard.

Funding: This was an investigator-initiated study without institutional or industrial funding.

Keywords: CIDP; Chronic inflammatory demyelinating polyneuropathy; Immunoadsorption; Long-term effects.

Fig. 1

Study flow diagram. Discrepancies between the sum of immunoadsorption (IA) and plasma exchange (PLEX) subgroups and the overall number of patients in each row is due to patients receiving both IA and PLEX.

Fig. 2

Short-term effects of IA and PLEX. Individual values for CIDP scores before (orange) and after (blue) each treatment cycle of IA (left) and PLEX (right). One cycle consists of 5 treatments. Data were collected 3 days before the first and directly after the last treatment of each cycle. CIDP: chronic inflammatory demyelinating polyneuropathy; IA: immunoadsorption; PLEX: plasma exchange.

Fig. 3

Long-term effects of IA and PLEX. Individual values for changes of CIDP score per month (blue) compared to preceding treatments with intravenous immunoglobulins and/or corticosteroids (orange) in patients receiving at last 2 cycles of IA (left) or PLEX (right). Negative values represent improvements of CIDP score. CIDP: chronic inflammatory demyelinating polyneuropathy; IA: immunoadsorption; PLEX: plasma exchange.

Fig. 4

Reduction rate of immunoglobulins. Individual values of 55 cycles showing immunoglobulin levels of IgG (left), IgA (center), and IgM (right) after the last treatment of each cycle (post, blue) compared to baseline (before first treatment of each cycle, orange). Ig: Immunoglobulin.