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19-12-2018 | Rheumatology | News | Article

Targeting IL-1 ‘may not be effective’ for erosive hand OA

medwireNews: Findings from a randomized trial indicate that treatment with the interleukin (IL)-1α and -1β inhibitor lutikizumab does not improve pain or imaging outcomes among patients with erosive hand osteoarthritis (OA).

However, this lack of efficacy occurred “despite adequate neutralization of IL-1α and IL-1β,” say Margreet Kloppenburg (Leiden University Medical Center, the Netherlands) and co-investigators.

Their findings add to evidence demonstrating that other pharmacologic therapies – including tumor necrosis factor inhibitors and hydroxychloroquine – do not have symptomatic efficacy in these patients.

Kloppenburg and colleagues’ phase IIa study included 131 participants with at least three tender or swollen interphalangeal joints, a hand pain score of 6 points or more on an 11-point scale, and radiographic evidence of at least one erosive interphalangeal joint.

As reported in the Annals of the Rheumatic Diseases, the 64 patients who were randomly assigned to receive subcutaneous lutikizumab 200 mg every 2 weeks did not experience significantly greater improvements in pain from baseline to week 16 than the 67 patients given placebo, with least squares mean decreases in the Australian/ Canadian Osteoarthritis Hand Index (AUSCAN) pain score of 9.2 and 10.7 points, respectively.

Moreover, least squares mean changes in AUSCAN function from baseline to week 16, as well as in tender and swollen joint counts from baseline to week 26, were comparable between the two groups.

Imaging analysis revealed that endpoints including the average number of new erosive joints, change in Kellgren–Lawrence score, and Osteoarthritis Research Society International joint space narrowing score, were also similar among patients treated with lutikizumab versus placebo.

Significant reductions in serum levels of both cytokines occurred among patients in the lutikizumab group compared with those in the placebo arm, however, and the drug “markedly affected” pharmacodynamic measures linked to IL-1 inhibition, such as neutrophil counts and high-sensitivity C reactive protein, say the researchers.

In all, 91% of lutikizumab-treated patients and 88% of those given placebo experienced adverse events, and serious adverse events were reported in 3% of patients in both groups. A significantly higher proportion of patients in the active treatment arm experienced injection site reactions (36 vs 16%) and neutropenia (19 vs 0%), but infection rates were lower among participants given lutikizumab (41 vs 51%), and no serious infections occurred over the study period.

Together, these results indicate that “[t]argeting IL-1 may not be effective for the treatment of erosive [hand] OA,” say Kloppenburg and team.

By Claire Barnard

medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

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