Drug Targeting IL-1 Not Effective in Treating Erosive HOA

A randomized trial found that lutikizumab, an anti-interleukin (IL)-1α/β dual variable domain immunoglobulin, did not improve pain or imaging outcomes in patients with erosive hand osteoarthritis (HOA) when compared to placebo.

For 24 weeks, patients received either placebo or lutikizumab 200 mg every two weeks. Eligible patients had ≥1 erosive and ≥3 tender and/or swollen hand joints. At the start of the trial and after 24 weeks, patients underwent bilateral hand radiographs and hand MRI of the hand most tender or swollen at baseline at baseline and week 26. A change in Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subdomain score from baseline to 16 weeks was the primary endpoint, and covariance models were evaluated as continuous endpoints.

News: Treatment with the IL-1α/β inhibitor #lutikizumab ‘may not be effective’ for erosive hand #osteoarthritis – phase IIa #ClinicalTrial results by Margreet Kloppenburg (from @LUMC_Leiden) & team. Full paper in @ARD_BMJ https://t.co/QL2qtDr7qj

— medwireNews (@medwireNews) December 19, 2018

Out of 132 randomized patients, 110 completed the trial (lutikizumab, n = 49; placebo, n = 61). After 16 weeks, AUSCAN pain scores did not significantly differ between the lutikizumab and placebo groups (least squares mean difference, 1.5 [95% CI –1.9 to 5.0]). Clinical and imaging endpoints also did not differ between the groups; pain, stiffness, grip strength and patient-reported outcomes were similar between lutikizumab and placebo patients. Lutikizumab patients had significantly lower serum high-sensitivity C reactive protein levels, IL-1α and IL-1β levels, and blood neutrophils. Lutikizumab patients also had more cases of injection site reactions and neutropaenia, as well as discontinuations due to adverse events (lutikizumab, 4/64; placebo, 1/67).

In a phase 2a, #randomised, double-blind study in patients with erosive #HOA, treatment with lutikizumab did lead to adequate #interleukin-1α (IL-1α) and IL-1β blockage, but did not lead to improved #pain or #imaging outcomes.https://t.co/Ra2ynUyDFy pic.twitter.com/ygU7pDWQxa

— Annals of the Rheumatic Diseases (@ARD_BMJ) December 16, 2018

One of the study’s limitations was that it ended after 26 weeks; more time may have demonstrated “a structural effect of lutikizumab” and detected “related pain and function improvement,” according to the researchers. Researchers also did not measure joint synovial fluid levels of lutikizumab, IL-1α and/or IL-1β, so IL-1α and IL-1β concentrations may have been lowered to a level not detected radiographically or clinically. “In addition, we have no adequate explanation for the low use of NSAIDs or analgesics, given the high average level of pain in patients at baseline,” the study authors added.

“In conclusion, despite adequate systemic lutikizumab pharmacodynamic effects, lutikizumab did not significantly improve clinical outcomes or imaging outcomes in patients with erosive HOA, compared with placebo, suggesting that targeting IL-1 may be ineffective for the treatment of erosive HOA,” the researchers wrote.

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Source: Annals of the Rheumatic Diseases