Efficacy and safety of tanezumab, NSAIDs, and placebo in patients with moderate to severe hip or knee osteoarthritis and a history of depression, anxiety, or insomnia: post-hoc analysis of phase 3 trials

Abstract

Objective: Treatment outcomes for chronic pain can be poor in patients with depression, anxiety, or insomnia. This analysis evaluated the efficacy and safety of subcutaneous tanezumab, nonsteroidal anti-inflammatory drugs (NSAIDs), and placebo in patients with osteoarthritis (OA) and a history of these conditions using data from three phase 3 studies.

Methods: A post-hoc analysis of data from two pooled placebo-controlled studies and one NSAID-controlled study of subcutaneous tanezumab. All patients had moderate to severe knee or hip OA that was inadequately controlled with standard-of-care analgesics. Efficacy outcomes were least-squares mean change from baseline to Week 16 in Western Ontario McMaster Universities OA Index (WOMAC) Pain, WOMAC Physical Function, Patient’s global assessment of OA, and EQ-5D-5L scores. Results were summarized for patients with and without a history of depression, anxiety, or insomnia at baseline.

Results: 1545 patients were treated in the pooled placebo-controlled studies (history of depression, 12%; anxiety, 8%; insomnia, 10%; any, 23%) and 2996 in the NSAID-controlled study (16%, 11%, 13%, 28%, respectively). In groups with positive histories, 38–80% took antidepressant or anxiolytic medications at baseline. Within treatments, largely similar improvements in efficacy outcomes were observed in patients with and without a history of depression, anxiety, or insomnia; the types of treatment-emergent adverse events were similar.

Conclusions: Patients with OA and a history of depression, anxiety, or insomnia did not appear to experience reduced efficacy outcomes or an altered safety profile in response to tanezumab or NSAID treatment as compared with those without. NCT02697773; NCT02709486; NCT02528188

Keywords:

• Analgesics
• chronic pain
• comorbidity
• mood disorders

Transparency

Declaration of funding

These studies were sponsored by Pfizer and Eli Lilly and Company. Role of the Funder/Sponsor: Pfizer and Eli Lilly and Company contributed to the study design; Pfizer contributed to the management and collection of data. In their role as authors, employees of Pfizer and Eli Lilly were involved in the interpretation of data, preparation, review, and approval of the manuscript and the decision to submit for publication, along with their co-authors. The study sponsors approved the manuscript from an intellectual property perspective but had no right to veto the publication.

Declaration of financial/other relationships

P. Mease has received research support, consultation fees and/or speaker honoraria from AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, SUN Pharma, and UCB. L. Kuritzky has been a consultant to Lilly, Novo Nordisk, Sanofi Aventis, Janssen, Boehringer Ingelheim, Takeda, and Daiichi Sankyo. W.L. Wright has been a speaker for Pfizer, Merck, Sanofi, Biohaven, and Allergan, and a consultant for Pfizer, Merck, Sanofi, GlaxoSmithKline, and Gilead. T. Mallick-Searle has participated in the speaker’s bureau for AbbVie, Allergan, and Eli Lilly and Company. R. Fountaine, R. Yang, M. Sadrarhami, and W. Faison are/were employees of Pfizer and hold stock/stock options. E. Johnston and L. Viktrup are employees of Eli Lilly and Company and hold stock/stock options. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors made substantial contributions to the conception or design of the work, or the acquisition, analysis, or interpretation of the data; participated in drafting the manuscript and revising it for important intellectual input; approved the final draft and agreed to be accountable for the work.

Acknowledgements

Medical writing support was provided by Jennifer Bodkin of Engage Scientific Solutions and funded by Pfizer and Eli Lilly and Company. L. Kuritzky is affiliated with the University of Florida. The opinions expressed in this article do not reflect the opinions of the University of Florida. W. Faison authored and approved the initial draft of this manuscript but passed away before acceptance for publication. The authors acknowledge the contribution of Warachal to this research and publication.

Data availability statement

Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.

Notes

i WOMAC 1996 Nicholas Bellamy. WOMAC is a registered trademark of Nicholas Bellamy (CDN, EU, USA).