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Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1? and anti-interleukin-1? dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis.

ABSTRACT: OBJECTIVE:To assess the efficacy, safety, pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1?/? dual variable domain immunoglobulin lutikizumab (ABT-981) in erosive hand osteoarthritis (HOA). METHODS:Patients with ?1 erosive and ?3 tender and/or swollen hand joints were randomised to placebo or lutikizumab 200?mg subcutaneously every 2 weeks for 24 weeks. The primary endpoint was change in Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subdomain score from baseline to 16 weeks. At baseline and week 26, subjects had bilateral hand radiographs and MRI of the hand with the greatest number of baseline tender and/or swollen joints. Continuous endpoints were assessed using analysis of covariance models, with treatment and country as main factors and baseline measurements as covariates. RESULTS:Of 132 randomised subjects, 1 received no study drug and 110 completed the study (placebo, 61/67 (91%); lutikizumab, 49/64 (77%)). AUSCAN pain was not different among subjects treated with lutikizumab versus placebo at week 16 (least squares mean difference, 1.5 (95% CI -1.9 to 5.0)). Other clinical and imaging endpoints were not different between lutikizumab and placebo. Lutikizumab significantly decreased serum high-sensitivity C reactive protein levels, IL-1? and IL-1? levels, and blood neutrophils. Lutikizumab pharmacokinetics were consistent with phase I studies and not affected by antidrug antibodies. Injection site reactions and neutropaenia were more common in the lutikizumab group; discontinuations because of adverse events occurred more frequently with lutikizumab (4/64) versus placebo (1/67). CONCLUSION:Despite adequate blockade of IL-1, lutikizumab did not improve pain or imaging outcomes in erosive HOA compared with placebo.

SUBMITTER: Kloppenburg M

PROVIDER: S-EPMC6390132 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1α and anti-interleukin-1β dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis.

Kloppenburg Margreet M Peterfy Charles C Haugen Ida K IK Kroon Féline F Chen Su S Wang Li L Liu Wei W Levy Gwen G Fleischmann Roy M RM Berenbaum Francis F van der Heijde Désirée D Bansal Prashant P Wittoek Ruth R Feng Sheng S Fang Yuni Y Saltarelli Mary M Medema Jeroen K JK Levesque Marc C MC

Annals of the rheumatic diseases 20181214 3

<h4>Objective</h4>To assess the efficacy, safety, pharmacokinetics and pharmacodynamics of the anti-interleukin (IL)-1α/β dual variable domain immunoglobulin lutikizumab (ABT-981) in erosive hand osteoarthritis (HOA).<h4>Methods</h4>Patients with ≥1 erosive and ≥3 tender and/or swollen hand joints were randomised to placebo or lutikizumab 200 mg subcutaneously every 2 weeks for 24 weeks. The primary endpoint was change in Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain subdomain scor ...[more]

PMID: 30552176

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Project description:BackgroundMany patients with hand osteoarthritis (HOA) experience reduced health-related quality of life. This study sought to better understand the disease and treatment experience of individuals with HOA, explore any differences in experiences between erosive and non-erosive HOA sub-types, and evaluate content validity of the Michigan Hand Outcomes Questionnaire (MHQ) in HOA.MethodsThirty subjects from the United States (n = 15 erosive HOA; n = 15 non-erosive HOA) participated in semi-structured interviews: concept elicitation explored symptoms/impacts important to patients; cognitive interviews assessed understanding and relevance of the MHQ. A sub-sample participated in real-time data capture (RTDC) activities via a smartphone/tablet app over 7 days. Verbatim transcripts were coded using Atlas.ti software and thematically analyzed. Concept saturation and MHQ content validity were evaluated.ResultsMost participants reported experiencing pain, swelling and stiffness, symptoms that most commonly had a direct impact on physical functioning. Substantial impacts on activities of daily living, emotional functioning, sleep and work were also reported. RTDC findings corroborated concept elicitation findings. There were no notable differences between erosive and non-erosive HOA, except nodules were reported more frequently in erosive disease. Most participants used analgesic treatments, but effects were short-lived. Pain was the symptom most frequently reported as most bothersome and important to treat. Concept saturation was achieved. MHQ items and instructions were well understood and relevant to most participants; stiffness and swelling were reported as important symptoms not included in the MHQ.ConclusionsThis study characterizes key symptoms of HOA which are burdensome for patients and not well controlled by current therapies, highlighting an unmet treatment need. Although the study is limited by a small sample size that may not be representative of the broader erosive and non-erosive HOA population, concept saturation was achieved, and our findings suggest that disease experience is similar for patients with erosive and non-erosive HOA. Evaluation of stiffness and swelling items in conjunction with the MHQ may enhance relevance and improve measurement precision to assess important domains of HQRoL in an HOA population.

Dataset Information

Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1? and anti-interleukin-1? dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis.

Publications

Phase IIa, placebo-controlled, randomised study of lutikizumab, an anti-interleukin-1α and anti-interleukin-1β dual variable domain immunoglobulin, in patients with erosive hand osteoarthritis.

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