Treatment of Idiopathic Recurrent Pericarditis With Goflikicept
- In a small industry-sponsored and industry-authored phase II/III study performed at two sites in Russia, treatment with the IL-1 inhibitor goflikicept in one of two different dosing regimens was associated with treatment response for idiopathic recurrent pericarditis (IRP).
- Of 20 patients in a randomized withdrawal period, goflikicept was superior to placebo in preventing recurrences of IRP through 24 weeks of therapy.
What is the efficacy and safety of the interleukin (IL)-1 inhibitor goflikicept in the treatment of idiopathic recurrent pericarditis (IRP)?
In an industry-sponsored study performed at two sites in Russia, goflikicept was studied in patients with IRP with and without recurrence at time of enrollment. The study consisted of four periods: screening, run-in (open-label treatment using two different goflikicept dosing regimens), randomized withdrawal (with placebo control), and follow-up. Treatment response was defined as 3 of 3 criteria of chest pain ≤3 on a score of 1-10, C-reactive protein (CRP) ≤5 mg/L, and absent or small pericardial effusion on echocardiography; recurrence of pericarditis was defined as ≥2 of 3 criteria of chest pain >3, CRP >5 mg/L, and new or progressive diastolic pericardial effusion on echocardiography. The primary study endpoint was time to first pericarditis recurrence during the randomized withdrawal period; secondary endpoints were change from baseline chest pain, CRP and biomarker levels, pericardial effusion size on echocardiography, glucocorticoid withdrawal, and change in quality of life assessed using the Short Form-36 Health Survey. Only patients with a clinical response to goflikicept in the run-in period were randomized 1:1 to a placebo-controlled withdrawal period, during which the primary endpoint was evaluated.
A total of 22 patients were enrolled, including 13 in remission and nine with recurrent IRP at the time of enrollment. Of those 22 patients, 21 achieved treatment response (including eight of nine with recurrence at the time of enrollment) accompanied by reductions in chest pain, CRP, and pericardial effusion; and 20 were randomized during the randomized withdrawal period. Recurrence of pericarditis occurred in 9 of 10 patients in the placebo group (median time to recurrence 50 [6 to 84] days) with no recurrences in the goflikicept group within 24 weeks after randomization (p < 0.001). There were statistically significant differences between the goflikicept group and the placebo group in change in physical functioning scale score between baseline and day 56 (5.0 [-5.0 to 10.0] vs. -15.0 [-17.5 to -7.5], p = 0.02) and change in IL-1 receptor antagonist levels between baseline and day 56 (-9 [-55 to -59 pg/mL vs. 766 [408 to 968] pg/mL, p < 0.009). A total of 122 adverse events were reported in 21 patients (96%), with no deaths and no new safety signals identified for goflikicept.
The authors conclude that treatment with goflikicept prevented IRP recurrences and maintained IRP remission with a favorable risk-benefit ratio, and that goflikicept reduced the risk of IRP recurrence compared to placebo.
IRP is a rare, complex autoinflammatory disease with excessive synthesis of proinflammatory cytokines in the IL-1 family. Goflikicept is a novel heterodimeric (targeting two different antigens) fusion protein capable of high-affinity binding to human IL-1ß and IL-1α. This small, industry-sponsored and industry-authored phase II/III study describes in a difficult-to-read report that treatment with goflikicept in one of two dosing regimens was associated with treatment response for IRP (eight of nine subjects with recurrent pericarditis at the time of enrollment responded to open-label treatment), and that goflikicept was superior to placebo in preventing recurrences of IRP through 24 weeks of therapy. The concept of using anti-cytokine biologics for the treatment of IRP is of interest; as could be larger, investigator-controlled, multicenter trials of goflikicept that also include more objective evidence (e.g., magnetic resonance imaging) of pericardial inflammation and an independent review committee.
Keywords: Biomarkers, Chest Pain, Chronic Disease, C-Reactive Protein, Diagnostic Imaging, Echocardiography, Glucocorticoids, Hereditary Autoinflammatory Diseases, Interleukin 1 Receptor Antagonist Protein, Interleukins, Pericardial Effusion, Pericarditis, Primary Prevention, Quality of Life
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