Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated peripheral nerve disorder with an indeterminate prognosis requiring long-term dependence on immunotherapy. The 2021 multicenter GRIPPER study, co-authored by Thomas H. Brannagan, MD, Director of the Peripheral Neuropathy Center at NewYork-Presbyterian/
Dr. Thomas Brannagan
Some 30 percent of patients with CIDP are able to attain a long-lasting period of drug-free remission at some point in their disease. But there are no known disease activity biomarkers that predict what dose, frequency, or duration of immunotherapy is needed, or even if immunotherapy is warranted at all. The method of determining disease activity involves weaning or discontinuing immunotherapy followed by monitoring for changes in clinical outcomes. Objective deterioration occurring after ceasing immunotherapy indicates – but does not prove – that the disease is active and that immunotherapy is the appropriate treatment.
In the GRIPPER study, the researchers prospectively recorded daily grip strength and weekly disability outcomes in patients with CIDP being treated with IVIG. They then calculated intra-IVIG-cycle changes in grip strength compared to the pre-IVIG baseline and correlated these changes with disability. Of 25 patients, 48 percent had little or no grip strength fluctuations in between IVIG infusions, while 52 percent had substantial fluctuations. The research team concluded that intra-IVIG-cycle grip strength fluctuations reveal a difficult to measure fundamental biologic process and that by quantifying these fluctuations, IVIG optimization can be accomplished more precisely.
Most recently, Dr. Brannagan again joined Dr. Allen in a related multicenter study that aimed to explore the impact that real-time treatment-related fluctuations have on long-term CIDP prognosis, strength impairment, and disability. The researchers sought to determine if these fluctuations can predict the ability to reach drug-free remission; offer further understanding of IVIG or other immunotherapy utilization patterns; and predict deteriorations in strength and disability. To that end, the research team conducted a retrospective observational cohort review of data from the patients who participated in the original GRIPPER study.
Minor treatment-related fluctuations are unlikely to result in substantial accumulation of disability over time. These findings provide reassurance that emergence of modest end-of-cycle symptoms during IVIG treatment may not always necessitate escalation in IVIG dose or infusion frequency.
— Study authors, Muscle & Nerve, November 4, 2022
Their findings, which were published in the November 4, 2022, online issue of Muscle & Nerve, showed that:
- After a mean follow-up of 44.7 months, there were no differences in baseline or follow-up strength or disability scores in patients with a low number of fluctuations compared to those with a high number of fluctuations
- In both groups, about one-third of patients achieved drug-free remission
The authors concluded that treatment-related fluctuations are important to identify in order to optimize treatment in real time, but they are poor forecasters of disease activity long-term. The authors wrote, “Minor treatment-related fluctuations are unlikely to result in substantial accumulation of disability over time. These findings provide reassurance that emergence of modest end-of-cycle symptoms during IVIG treatment may not always necessitate escalation in IVIG dose or infusion frequency.”
Nevertheless, the investigators emphasized that while treatment-related fluctuations, if present, were largely mild, they could not eliminate the possibility that end-of-cycle deteriorations would result in increasing disability over time. “Instead,” they wrote, “our findings (together with CIDP treatment guidelines) suggest an approach to management that balances optimization of treatment to achieve a state of minimal expression of manifestations with tolerance to some treatment-related fluctuations.”
The researchers also advocate for evidence-based approaches that use objective outcomes of strength impairment and disability to validate treatment response that can be used to optimize IVIG dose and frequency tailored to the needs of each patient.
