Outcome measures and biomarkers in chronic inflammatory demyelinating polyradiculoneuropathy: from research to clinical practice

ABSTRACT

Introduction: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated syndrome characterized clinically by weakness and/or numbness that evolves over 2 months or more. The heterogeneity of clinical features necessitates an individualized approach to disease monitoring that takes lessons learned from clinical trials and applies them to clinical practice.

Areas covered: This review discusses the importance of clinimetrics and biomarkers in CIDP diagnosis and disease monitoring. Highlighted are the challenges of defining responses to immunotherapy, the usefulness, and limitations of utilizing evidence-based clinical outcome measures during routine clinical care, and the evolving understanding of how diagnostic and disease activity biomarkers may reshape our treatment and disease monitoring paradigms.

Expert opinion: Although disability and impairment outcome measures are commonly used in CIDP to indicate disease status, the nonspecific nature of these metrics limits the ability to attribute a change in any given metric to a change in CIDP. This interpretive challenge may be magnified by inconsistencies in the direction of change as well as a strong placebo effect. There is a need to improve our understanding of minimally important changes in existing outcome measures as a means to personalize treatment and to better assess disease activity status with biomarker discovery.

KEYWORDS:

• Chronic inflammatory demyelinating polyradiculoneuropathy
• clinical outcome measures
• biomarkers
• diagnosis
• disease activity
• disability
• impairment
• minimal clinically important difference

Article highlights

• Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare and heterogeneous immune-mediated peripheral nerve syndrome with several clinical variants.

• Since CIDP misdiagnosis and overtreatment is common, diagnostic and disease activity biomarkers are needed to improve diagnostic accuracy and guide treatment decisions.

• In clinical trials, CIDP outcome measures commonly used include metrics for disability, impairment, and quality of life.

• In clinical practice, the collection of structured outcome measures to support a diagnosis and treatment response is highly variable and frequently inadequate.

• There is an evolving understanding of the minimum clinically important difference (MCID) for outcome measures typically followed in patients with CIDP. The rigidity of MCID interpretation in clinical trials may not always be needed in clinical practice when outcomes of different domains are in agreement. Interpreting MCID becomes challenging when multiple metrics point in different directions.

• Although the quest for biomarkers that reflect the underlying pathobiology and outcomes of CIDP has been underway for more than a decade, robust biomarkers for diagnosis and disease monitoring are still lacking.

• Some areas of biomarker research include tissue status, effector mechanisms, nerve function, and drug effect.

• Ideally, a panel of CIDP biomarkers will emerge that can be utilized selectively to capture the full spectrum of CIDP diagnostic heterogeneity and facilitate disease monitoring across a wide range of clinical scenarios.

• The international registry Inflammatory Neuropathy Consortium Base (INCbase) aims to collect a standard set of clinical outcomes and biomaterials from patients across the CIDP spectrum. The study expects to uncover enlightening clinical and biological data to better define the boundaries and immunologic underpinnings of CIDP.

Acknowledgments

Editorial assistance was provided by Robert Furlong and Kerry Dechant on behalf of Content Ed Net (Madrid, Spain) with funding from Grifols SA (Barcelona Spain).

Declaration of interest

JA Allen has received consulting fees from Argenx, Alexion, Akcea, CSL Behring, Grifols, and Takeda, speaker honorarium from Akcea and CSL Behring. F Eftimov has received grants for research in CIDP from ZonMw (a Dutch governmental agency) and Prinses Beatrix Spierfonds (Dutch Charity Funds). As principal investigator of INCbase, an international registry for CIDP, he has received grants for investigator-initiated studies within INCbase from various pharmaceutical companies. All grants were paid to his institution. He has received speakers fee from CSL Behring, Kedrion Biopharma and Grifols. Also he has received departmental honoraria for serving on scientific advisory boards of CSL Behring, UCB pharma and Takeda Pharmaceuticals. L Querol has received research grants from Instituto de Salud Carlos III Ministry of Economy and Innovation Spain, GBS CIDP Foundation International, Grifols, Novartis Pharma Spain, and Roche; has provided expert testimony to Alexion, Annexon, CSL Behring, Grifols, Merck, Novartis, Roche, Sanofi Genzyme, and UCB; serves on Clinical Trial Steering Committees for Sanofi Genzyme and UCB. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The manuscript was developed from the proceedings of a Grifols-sponsored virtual symposium, held on 28 October 2020 as part of the 2020 Peripheral Nerve Society Virtual Event.