medwireNews: Subcutaneous efgartigimod PH20 shows potential for reducing the risk for relapse in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) who respond to the treatment, shows the ADHERE study published in The Lancet Neurology.
The investigators examined the efficacy and safety of efgartigimod, a human immunoglobulin G1 antibody fragment that binds to the neonatal fragment crystallizable receptor (FcRn), co-formulated with recombinant human hyaluronidase PH20 in CIPD patients from 146 clinics across Asia-Pacific, North America, and Europe between 2020 and 2023.
The study involved two stages. Stage A was an open-label phase involving 322 patients (mean age 54 years, 65% men) who received subcutaneous efgartigimod PH20 at a weekly dose of 1000 mg for up to 12 weeks. Of these patients, 20% had previously received treatment with corticosteroids and 51% with intravenous or subcutaneous immunoglobulins, while 29% were considered off-treatment having not received any treatment in the previous 6 months.
Previous treatments were withdrawn during a preceding 12-week run-in phase, during which all patients, including those off-treatment, showed clinical deterioration, defined as at least a 1-point increase in the adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT) score, at least a 4-point reduction on the centile Inflammatory Rasch-built Overall Disability Scale (I-RODS), or a decline of 8 kPa or more in grip strength.
A total of 214 (66%) patients responded to treatment during phase A, showing improvement in the aINCAT (≥1 point), I-RODS (≥4 points), or grip strength (≥8 kPa), with 40% of the 322 patients doing so by week 4.
Jeffrey Allen (University of Minnesota, Minneapolis, USA) and colleagues note that patients responded to efgartigimod PH20 irrespective of previous CIDP treatment, but the response rate was lower among patients who had previously been taking immunoglobulins than those who had previously taken corticosteroids and those off-treatment, at 59% versus 78% and 72%, respectively.
They add that “early discontinuations were relatively more common in the previous intravenous or subcutaneous immunoglobulin subgroup,” at a corresponding 32% versus 13% and 9%.
In all, 211 of the 214 patients who responded to treatment in stage A were enrolled in stage B of the study. They were randomly assigned to receive subcutaneous efgartigimod PH20 1000 mg/week (n=111) or placebo (n=110) for up to 48 weeks (mean 22.3 and 11.1 weeks, respectively).
Allen and team report that relapse, namely time to first aINCAT increase of at least 1 point, occurred in 27.9% of patients given efgartigimod PH20 versus 53.6% of those in the placebo arm, translating to a significant 61% reduction in risk in favor of the active treatment.
Contrary to treatment response, the reduction in relapse rates with efgartigimod PH20 relative to placebo was numerically greater among patients previously receiving immunoglobulins (28 vs 54%) and corticosteroids (21 vs 65%) than those who were off-treatment (31 vs 41%).
Given the “nuanced picture” in the prespecified subgroup analyses, Yusuf Rajabally (Aston University, Birmingham, UK) writes in a related comment that “[i]nterpretation of the detailed results of ADHERE is […] not straightforward.”
He points out that “[i]mmunoglobulin cessation shortly before entry into stage A might explain the poorer response in participants pretreated with immunoglobulins, which raises questions regarding the ideal time of a switch from immunoglobulins to FcRn blocker therapy, such as subcutaneous efgartigimod PH20.”
But he concludes that “after decades with little therapeutic progress, this study offers reasons for overall optimism and enthusiasm.”
Safety data from the two stages showed that in stage A, treatment-emergent adverse events (TEAEs) occurred in 63% of patients, with serious TEAEs occurring in 7%. In stage B, TEAEs occurred in 64% of patients in the efgartigimod group versus 56% in the placebo group, most commonly COVID-19 in both groups, and injection site reactions and upper respiratory tract infections, respectively. Serious TEAEs occurred in 5% of patients in each group. There were three deaths, all considered unrelated and unlikely to be related to treatment, two in the efgartigimod PH20 group and one in the placebo group.
The investigators highlight that efgartigimod PH20 has a “convenient” mode of administration, “being a subcutaneous single 5.6 mL injection lasting 30–90 s and with the potential for self-administration or caregiver administration.”
It is therefore “capable of improving CIDP symptoms while lessening the overall treatment burden compared with current standard of care.”
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