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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.

ABSTRACT: 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).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.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.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.NCT00486434 (trial 1) and NCT00704847 (trial 2).

SUBMITTER: Bihlet AR

PROVIDER: S-EPMC5773024 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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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.

Bihlet Asger Reinstrup AR Byrjalsen Inger I Bay-Jensen Anne-Christine AC Andersen Jeppe Ragnar JR Christiansen Claus C Riis Bente Juel BJ Valter Ivo I Karsdal Morten A MA Hochberg Marc C MC

BMC musculoskeletal disorders 20180117 1

<h4>Background</h4>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 categorie ...[more]

PMID: 29343266

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Project description:BackgroundRecent studies indicate that the administration of open-label placebos (OLP) can improve symptoms in various medical conditions. The primary aim of this 3-week randomized controlled trial was to examine the effects of OLP treatments on pain, functional disability, and mobility in patients with arthritic knee pain.MethodsSixty patients (55% females; mean age, 66.9 ± 9.7 SD years) were randomized to one of two OLP treatments (n = 41) or no treatment (NT; n = 19). OLP treatments were accompanied by the verbal suggestion "to decrease pain" (OLP-pain, n = 20) or "to improve mood" (OLP-mood, n = 21). Pain and mood levels were monitored on 11-point Numeric Rating Scales (NRSs) in a patient diary, and global clinical improvement (CGI-I) was assessed at the end of the study. At baseline and after 21 days, patients filled in validated questionnaires to assess symptoms and functional disability of the knee (WOMAC), mental and physical quality of life (SF-36), state anxiety (STAI-state), perceived stress (PSQ-20), and self-efficacy (GSE). In addition, knee mobility (neutral zero-method), heart rate variability (HRV), and diurnal cortisol levels were evaluated before and after treatment.ResultsEvaluation of daily pain ratings indicated significant pain decrease in the OLP groups compared to NT (p = 0.013, d = 0.64), with no difference between the OLP-pain and the OLP-mood groups (p = 0.856, d = 0.05). OLP treatment also improved WOMAC pain (p = 0.036, d = 0.55), again with no difference between the two OLP groups (p = 0.65, d = 0.17). WOMAC function and stiffness, knee mobility, stress, state anxiety, quality of life, and self-efficacy did not change differently between groups.ConclusionOLP treatment improved knee pain in elderly patients with symptomatic knee osteoarthritis (OA), while functional disability and mobility of the knee did not change. The content of the verbal suggestion was of minor importance. OLP administration may be considered as supportive analgesic treatment in elderly patients with symptomatic knee OA.Trial registrationGerman Clinical Trials Register (https://www.drks.de/), DRKS00015191 (retrospectively registered).

Project description:BackgroundMultiple surgical interventions exist for the treatment of symptomatic knee osteoarthritis, but the surgeon and patient may often have difficulty deciding which interventions are the best option.MethodsWe conducted a systematic review to identify randomized clinical trials (RCTs) that compared complications, revisions, reoperations, and functional outcomes among TKA (total knee arthroplasty), UKA (unicompartmental knee arthroplasty), HTO (high tibial osteotomy), BCA (bicompartmental knee arthroplasty), BIU (bi-unicompartmental knee arthroplasty), and KJD (knee joint distraction). The PubMed, Embase, and Cochrane databases were reviewed for all studies comparing two or more surgical interventions. Direct-comparison meta-analysis and network meta-analysis (NMA) were performed to combine direct and indirect evidence. The risk of bias was assessed using the revised Cochrane risk of bias tool for RCTs.ResultsThis NMA and systematic review included 21 studies (17 RCTs), with a total of 1749 patients. The overall risk-of-bias assessment of the RCTs revealed that 7 studies had low risk, 5 had some concerns, and 9 had high risk. SUCRA (the surface under the cumulative ranking curve) rankings revealed that KJD had the greatest risk of appearing postoperative complications, revisions, and reoperations, and UKA or TKA had the lowest risk. The majority of comparisons among various treatments showed no difference for functional outcomes.ConclusionEach surgical intervention is noninferior to other treatments in functional outcomes, but UKA and TKA are better options to treat OA according to SUCRA rankings by comparing complications, revisions, and reoperations. KJD is an imperfect option for treating OA. Other treatments should be carefully considered for each patient in accordance with their actual conditions. However, this conclusion is limited by the selection of reviewed publications and individual variation of surgical indications for patients.Trial registrationThis study was registered with Research Registry (reviewregistry1395).

Project description:BackgroundThere are no proven therapies that modify the structural changes associated with osteoarthritis (OA). Preclinical data suggests that intra-articular recombinant human BMP-7 (bone morphogenetic protein-7) has reparative effects on cartilage, as well as on symptoms of joint pain. The objective of this study was to determine the safety and tolerability as well as dose-limiting toxicity and maximal tolerated dose of intra-articular BMP-7. The secondary objectives were to determine the effect on symptomatic responses through 24 weeks.MethodsThis was a Phase 1, double-blind, randomized, multi-center, placebo-controlled, single-dose escalation safety study consisting of 4 dosing cohorts in participants with knee OA. Each cohort was to consist of 8 treated participants, with treatment allocation in a 3:1 active (intra-articular BMP-7) to placebo ratio. Eligible participants were persons with symptomatic radiographic knee OA over the age of 40. The primary objective of this study was to determine the safety and tolerability of BMP-7 including laboratory assessments, immunogenicity data and radiographic assessments. Secondary objectives were to determine the proportion of participants with a 20%, 50%, and 70% improvement in the WOMAC pain and function subscales at 4, 8, 12, and 24 weeks. Other secondary outcomes included the change from baseline to 4, 8, 12, and 24 weeks for the OARSI responder criteria.ResultsThe mean age of participants was 60 years and 73% were female. All 33 participants who were enrolled completed the study and most adverse events were mild or moderate and were similar in placebo and BMP-7 groups. The 1 mg BMP-7 group showed a higher frequency of injection site pain and there was no ectopic bone formation seen on plain x-rays. By week 12, most participants in both the BMP-7 and placebo groups experienced a 20% improvement in pain and overall the BMP-7 group was similar to placebo with regard to this measurement. In the participants who received 0.1 mg and 0.3 mg BMP-7, there was a trend toward greater symptomatic improvement than placebo. The other secondary endpoints showed similar trends including the OARSI responder criteria for which the BMP-7 groups had more responders than placebo.ConclusionsThere was no dose limiting toxicity identified in this study. The suggestion of a symptom response, together with the lack of dose limiting toxicity provide further support for the continued development of this product for the treatment of osteoarthritis.

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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.

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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.

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