Identification of pain categories associated with change in pain in patients receiving placebo: data from two phase 3 randomized clinical trials in symptomatic knee osteoarthritis
Asger Reinstrup Bihlet, Inger Byrjalsen, Anne-Christine Bay-Jensen, Jeppe Ragnar Andersen, Claus Christiansen, Bente Juel Riis, Ivo Valter, Morten A Karsdal, Marc C Hochberg, Asger Reinstrup Bihlet, Inger Byrjalsen, Anne-Christine Bay-Jensen, Jeppe Ragnar Andersen, Claus Christiansen, Bente Juel Riis, Ivo Valter, Morten A Karsdal, Marc C Hochberg
Abstract
Background: Pain is the principal clinical symptom of osteoarthritis (OA), and development of safe and effective analgesics for OA pain is needed. Drug development of new analgesics for OA pain is impaired by substantial change in pain in patients receiving placebo, and more data describing clinical characteristics and pain categories particularly associated with this phenomenon is needed. The purpose of this post-hoc analysis was to investigate clinical characteristics and pain categories and their association with radiographic progression and placebo pain reduction (PPR) in OA patients as measured the Western Ontario and McMasters Arthritis (WOMAC).
Methods: Pooled data from the placebo groups of two phase III randomized clinical trials in patients with knee OA followed for 2 years were analyzed. Differences between individual sub-scores and pain categories of weight-bearing and non-weight bearing pain over time were assessed. Selected patient baseline characteristics were assessed for association with PPR. Association between pain categories and radiographic progression was analyzed.
Results: The reduction of pain in placebo-treated patients was significantly higher in the composite of questions related to weight-bearing pain compared to non-weight-bearing pain of the target knee. Baseline BMI, age and JSW were not associated with pain change. Pain reduction was higher in the Target knee, compared to the Non-Target knee at all corresponding time-points. A very weak correlation was found between weight-bearing pain and progression in the non-target knee.
Conclusions: These results indicate that the reduction in pain in patients treated with placebo is significantly different between pain categories, as weight-bearing pain was significantly more reduced compared to non-weight-bearing pain. Further research in pain categories in OA is warranted.
Trial registration: NCT00486434 (trial 1) and NCT00704847 (trial 2).
Keywords: Pain categories; Placebo-response; Radiographic progression.
Conflict of interest statement
Ethics approval and consent to participateThe conduct of both trials was approved by all applicable national regulatory authorities, independent review boards and ethical committees. All participating subjects gave a written, informed consent to participate in the trial, including consent to publish results from the trial.
Competing interestsARB, IB, ACBJ, CC, BJR, JRA, and MAK are full-time employees in Nordic Bioscience, a company engaged in biomarker research and development of treatments for OA. ARB, ACBJ, CC, BJR, JRA and MK are shareholders of Nordic Bioscience. BJR and CC are major shareholders and board members of Nordic Bioscience. IV is a full-time employee of BioClinica. MH does not have any conflicts of interest to declare.
Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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