Background/Purpose: Tanezumab is under investigation for the treatment of moderate to severe OA pain. As part of the phase 3 OA program, two randomized, placebo-controlled studies were completed and the data reported separately. Both studies showed early and sustained pain relief, following subcutaneous administration of tanezumab, at the time of the respective primary endpoints. The objective of this pooled analysis of 2 studies was to evaluate the treatment response of tanezumab versus placebo as assessed by reductions in the WOMAC Pain subscale of ≥30%, ≥50%, ≥70% or ≥90% at Week 16. Reductions from baseline of ≥30% (moderate) or ≥50% (substantial) are often reported to be clinically important improvements.

Methods: Both phase 3 studies were randomized, double-blind, and placebo-controlled. Study 1, with primary endpoint at Week 24, enrolled patients from Europe or Japan (NCT02709486) who then received 3 doses of placebo, tanezumab 2.5 mg or tanezumab 5 mg (at baseline, Week 8 and Week 16). Study 2, with primary endpoint at Week 16, was a dose-titration study conducted in North America (NCT02697773) with three arms: placebo at baseline and Week 8, tanezumab 2.5 mg at baseline and Week 8, or tanezumab 2.5 mg at baseline and tanezumab 5 mg at Week 8. Data from this study’s dose-titration group (tanezumab 2.5 mg to 5 mg at Week 8) were pooled with the study 1 tanezumab 5 mg group for analyses at Week 16. Eligibility criteria included OA diagnosis (hip or knee, ACR criteria, Kellgren-Lawrence grade ≥2); WOMAC Pain and Physical Function scores ≥5; Patient’s Global Assessment of Osteoarthritis ‘fair’, ‘poor’ or ‘very poor’; and a history of acetaminophen, nonsteroidal anti-inflammatory drugs, and tramadol/opioids being inadequate or unsuitable. The proportions of patients with ≥30%, ≥50%, ≥70% or ≥90% reduction from baseline at Week 16 in WOMAC Pain were estimated by logistic regression.

Results: A total of 1545 patients were evaluated. The index joint was the knee for 84.1% (1299/1545) of patients. Radiographic severity of the index joint was Kellgren-Lawrence grade 3 or 4 for 77.1% (1191/1545) of patients. Baseline WOMAC Pain scores were 6.9 ± 1.1 (mean ± standard deviation) in all three pooled groups. The proportion of patients achieving improvement from baseline in WOMAC Pain at Week 16 of ≥30% (55.6%, 68.0% and 69.4% in the placebo, tanezumab 2.5 mg and tanezumab 5 mg groups, respectively), ≥50% (36.8%, 51.9% and 51.8%, respectively), or ≥70% (20.7%, 27.9% and 29.8%, respectively) was significantly greater in both tanezumab treatment groups compared with the placebo group (all P< 0.05 versus placebo; Figure 1). The proportion of patients with ≥90% improvement was significantly greater in the tanezumab 2.5 mg group (10.7%; P< 0.05), but not in the tanezumab 5 mg group (9.1%), compared with the placebo group (6.0%).

Conclusion: The pooled analysis of these studies showed that at Week 16, a significantly higher proportion of patients achieved a clinically important improvement in pain when treated with tanezumab (both treatment groups) than placebo, with little difference between the tanezumab treatment groups. Funded by Pfizer and Lilly.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinically-important-improvement-in-osteoarthritis-pain-at-week-16-after-subcutaneous-administration-of-tanezumab-pooled-analysis-from-international-studies/