The Role of PRP and Its Platelet Concentration in Improving WOMAC Score on Early-Stage Knee Osteoarthritis (OA) Patients

We present a phase 1 study that utilizes a crossover design that provides a rapid and relatively inexpensive methodology for evaluating a new transdermal product. The treatment for osteoarthritis (OA) aims to reduce pain and improve function. An innovative magnetophoresis technology has been developed that facilitates transdermal delivery of ibuprofen. The study used measures that were taken over a relatively short time period to monitor the pharmacodynamic response to ibuprofen. Each participant received magnetophoresis-enhanced transdermal ibuprofen or placebo in randomised order, with a five-day washout period. The participants were 24 volunteers with medically diagnosed, painful knee OA. The primary outcome measures were VAS rating of pain on movement and Western Ontario and McMaster Universities (WOMAC) pain and function scores. VAS for pain on movement (p < 0.001), WOMAC pain score (p = 0.004), and WOMAC function score (p = 0.004) were all significantly improved. There was a significant reduction in movement-related pain (p < 0.05) during the first patch application and for the remainder of the study period. The number needed to treat for a 50% reduction in movement related pain was 2.2. The study showed a rapid and significant analgesic effect in response to transdermal ibuprofen. A short trial of this nature can be used for informing the parameters that are required for a major randomised controlled trial.

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T2 mapping evaluation of changes in cartilage matrix after PRP and HA injection therapy in knee osteoarthritis: a prospective, randomized, double blind, placebo controlled study

10.21203/rs.3.rs-36493/v1 ◽

2020 ◽

Author(s):

Matjaz Vogrin ◽

Jakob Naranda ◽

Mario Gorenjak ◽

Tomaz Bajec ◽

Domen Mongus ◽

...

Keyword(s):

Placebo Group ◽

Knee Osteoarthritis ◽

Pain Score ◽

T2 Mapping ◽

Womac Score ◽

Controlled Study ◽

Womac Pain ◽

Womac Pain Score ◽

Knee Oa

Abstract BackgroundIn this study we focused on evaluating the effect of intra-articular platelet-rich plasma (PRP) and hyaluronic acid (HA) on the qualitative and quantitative properties of the articular cartilage in patients with knee osteoarthritis (OA).MethodsWe evaluated 264 patients undergoing treatment of moderate knee OA. Patients aged between 40 and 70 years were included with articular K-L stage ≤ 2. Patients were randomized into three groups and treated with three doses of intra-articular PRP, HA, or placebo injection. Patients were evaluated clinically and by using T2 mapping.ResultsBoth PRP (619.05 ± 243 ms; p = 2.7 × 10− 5) and HA (637.12 ± 273 ms; p = 1.×10− 4) group showed statistically significant lower post-application T2 relaxation times in comparison to the placebo group (859.80 ± 406 ms).Cartilage thickness increased significantly after PRP (2.41±0.87 vs. 2.58±0.97 mm, p=0.033) and HA (2.28±0.81 vs. 2.80±1.00 mm, p=1.8×10) applications. There was a significant decrease in WOMAC pain score by 30% (p=0,001) and the overall WOMAC score by 27 p=1.9×10-4%) in PRP group. The decrease in WOMAC pain score and the overall WOMAC score in the placebo group was similar to the results observed in the PRP group. In the HA group a significant decrease in WOMAC pain score by 14% (p=0,005) was observed only at the first follow-up, whereas no difference was observed at the second follow-up. ConclusionsT2 mapping of cartilage tissue may aid to monitor its properties after the intra-articular therapies in knee OA. However, there is a discrepancy between clinical findings and the results of T2 mapping, suggesting questionable grounds for applying intra-articular therapy.

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Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis

10.21203/rs.2.13667/v1 ◽

2019 ◽

Author(s):

Li Li ◽

Zhenxing Li ◽

Yuyan Li ◽

Xi Hu ◽

Yu Zhang ◽

...

Keyword(s):

Neuropathic Pain ◽

Synovial Fluid ◽

Knee Osteoarthritis ◽

Inflammatory Mediators ◽

Early Stage ◽

Womac Score ◽

Womac Pain ◽

Womac Pain Score ◽

Pain Scores ◽

Tnf Α

Abstract Background: Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, the expression of inflammatory mediators is controversial and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study is to identify the SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. Methods: The levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured in 86 patients using enzyme-linked immunosorbent assays. Nociceptive pain was measured using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was measured using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. Results: Pain scores measured using different methods were highly correlated to each other. The worse the pain, the worse the K-L grade and knee function were. The expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS was positively correlated to age, K-L grade, and the WOMAC score and negatively correlated to ROM and TNF-α expression. The VAS was positively correlated to age, K-L grade, and the WOMAC score but negatively correlated to ROM and the levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score was not correlated to any of the measured inflammatory mediators; it correlated to only ROM. The PainDETECT score correlated to only the WOMAC score. The expression of other inflammatory mediators was not correlated to any of the pain scores. Conclusions: IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlated to pain. The measured catabolic enzymes and neuropeptides are not correlated to nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

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Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis

10.21203/rs.2.13667/v4 ◽

2020 ◽

Author(s):

Li Li ◽

Zhenxing Li ◽

Yuyan Li ◽

Xi Hu ◽

Yu Zhang ◽

...

Keyword(s):

Neuropathic Pain ◽

Synovial Fluid ◽

Knee Osteoarthritis ◽

Inflammatory Mediators ◽

Early Stage ◽

Womac Score ◽

Womac Pain ◽

Womac Pain Score ◽

Pain Scores ◽

Tnf Α

Abstract Background: Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. Methods: Levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. Results: Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores. Conclusions: IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

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Profiling of inflammatory mediators in the synovial fluid related to pain in knee osteoarthritis

10.21203/rs.2.13667/v3 ◽

2019 ◽

Author(s):

Li Li ◽

Zhenxing Li ◽

Yuyan Li ◽

Xi Hu ◽

Yu Zhang ◽

...

Keyword(s):

Neuropathic Pain ◽

Synovial Fluid ◽

Knee Osteoarthritis ◽

Inflammatory Mediators ◽

Early Stage ◽

Womac Score ◽

Womac Pain ◽

Womac Pain Score ◽

Pain Scores ◽

Tnf Α

Abstract Background: Inflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA. Methods: Levels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale. Results: Pain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores. Conclusions: IL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

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Bioavailable turmeric extract for knee osteoarthritis: a randomized, non-inferiority trial versus paracetamol

Trials ◽

10.1186/s13063-021-05053-7 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Shubha Singhal ◽

Nazer Hasan ◽

Kirti Nirmal ◽

Rohit Chawla ◽

Shalini Chawla ◽

...

Keyword(s):

Adverse Events ◽

Knee Osteoarthritis ◽

Womac Score ◽

Secondary Outcome ◽

Womac Pain ◽

Knee Oa ◽

Turmeric Extract ◽

Tnf Α ◽

Pain Subscale ◽

And Function

Abstract Background To compare the efficacy and safety of bioavailable turmeric extract versus paracetamol in patients with knee osteoarthritis (OA). Methods In this randomized, non-inferiority, controlled clinical study, patients of knee OA were randomized to receive bioavailable turmeric extract (BCM-95®) 500 mg capsule two times daily or paracetamol 650 mg tablet three times daily for 6 weeks. The primary outcome measure was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. The secondary outcome measures were WOMAC total, WOMAC stiffness, and WOMAC physical function scores. Responder analysis of individual patients at different levels (≥ 20%, ≥ 50%, and ≥ 70%) for WOMAC score was calculated. TNF alpha and CRP levels were evaluated and adverse events (AE) were also recorded. Results Seventy-one and seventy-three knee OA patients, respectively in bioavailable turmeric extract and paracetamol groups, completed the study. Non-inferiority (equivalence) test showed that WOMAC scores were equivalent in both the groups (p value < 0.05) in all the domains within the equivalence limit defined by effect size (Cohen’s d) of 0.5 whereas CRP and TNF-α were better reduced with turmeric extract than paracetamol. After 6 weeks of treatment, WOMAC total score, pain, stiffness, and function scores got a significant improvement of 23.59, 32.09, 28.5, and 20.25% respectively with turmeric extract. In the turmeric extract group, 18% of patients got more than 50% improvement and 3% of patients got more than 70% improvement in WOMAC pain and function/stiffness score and none of the patients in the paracetamol group met the criteria. CRP and TNF-α got significantly reduced (37.21 and 74.81% respectively) in the turmeric extract group. Adverse events reported were mild and comparatively less in the turmeric extract group (5.48%) than in the paracetamol group (12.68%). Conclusion The results of the study suggest that bioavailable turmeric extract is as effective as paracetamol in reducing pain and other symptoms of knee osteoarthritis and found to be safe and more effective in reducing CRP and TNF-α. Trial registration Clinical Trials Registry – India CTRI/2017/02/007962. Registered on 27 February 2017

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Effect of Dextrose Prolotherapy, Platelet Rich Plasma and Autologous Conditioned Serum on Knee Osteoarthritis: A Randomized Clinical Trial

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v19i3.3452 ◽

2020 ◽

Author(s):

Alireza Pishgahi ◽

Rozita Abolhasan ◽

Seyed Kazem Shakouri ◽

Mohammad Sadegh Soltani-Zangbar ◽

Shahla Dareshiri ◽

...

Keyword(s):

Clinical Trial ◽

Knee Osteoarthritis ◽

Randomized Clinical Trial ◽

Platelet Rich Plasma ◽

Womac Score ◽

Knee Function ◽

Post Intervention ◽

Knee Oa ◽

Autologous Conditioned Serum ◽

And Function

Knee osteoarthritis (OA) is one of the common degenerative articular disorders that are related to decreased quality of life. Currently, novel biologic therapeutic approaches are introduced in the literature for OA management. In this study, the clinical efficiency of Dextrose prolotherapy, platelet-rich plasma (PRP) and autologous conditioned serum (ACS) injection on the level of pain and function in Knee OA were compared. A randomized clinical trial was directed on 92 knee OA patients. Patients were randomly divided into three groups: 30 were received dextrose prolotherapy once in a week for three weeks, 30 received autologous PRP for two times with seven days interval, and in the remaining 32 patients 2ml of ACS were injected two times every seven days. Study participants were measured through the Western Ontario and McMaster Universities (WOMAC) score, the visual analogue scale (VAS), at baseline, 1 and 6 months post-intervention. Both ACS and PRP treated patients showed improvement in pain intensity and knee function during 1 and 6 months pursue; however, this progress was more significant in the ACS group. Dextrose prolotherapy showed no substantial changes in pain and function of the affected knee in treated patients. Treatment of Knee OA with ACS and PRP injections are associated with pain reduction and knee function improvement. Not only, ACS therapy is more effective than that of PRP, but also due to its less variability in processing and less reported side effects, it could be considered as a safe and effective non-surgical alternative for OA management.

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Efficacy and Safety of Hylan versus Hyaluronic Acid in the Treatment of Knee Osteoarthritis

The Journal of Knee Surgery ◽

10.1055/s-0038-1641142 ◽

2018 ◽

Vol 32 (03) ◽

pp. 259-268 ◽

Cited By ~ 2

Author(s):

Wen-Li Dai ◽

Ze-Ming Lin ◽

Dong-Hong Guo ◽

Zhan-Jun Shi ◽

Jian Wang

Keyword(s):

Meta Analysis ◽

Womac Pain ◽

Efficacy And Safety ◽

Function Score ◽

Womac Pain Score ◽

Knee Oa ◽

Womac Function ◽

The Difference ◽

Level I ◽

And Function

AbstractThe purpose of this study was to use meta-analytic approach to compare the efficacy and safety of intraarticular hylan and hyaluronic acid (HA) for knee osteoarthritis (OA) treatment. We searched PubMed, Embase, and the Cochrane databases through July 2017 to identify Level I randomized controlled trials (RCTs) that evaluated clinical efficacy and safety of hylan compared with HA for knee OA. The primary outcomes were Visual Analogue Scale (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, and WOMAC function scores. In each study and for the outcome measures (VAS for pain, WOMAC pain, function and stiffness scores, and Lequesne score), we calculated the treatment effect from the difference between the preintervention and postintervention changes in the hylan and HA groups. Twenty-one RCTs involving 3,058 patients were included. Pooled analysis suggested that compared with HA, hylan was associated with similar pain relief and function improvement in patients with knee OA (VAS for pain: mean difference [MD], –3.04; 95% confidence interval [CI], –9.13 to 3.04; p = 0.33; I 2 = 76%. WOMAC pain score: MD, 0.23; 95% CI, –0.25 to 0.70; p = 0.35; I 2 = 0%. WOMAC function score: MD, –0.47; 95% CI, –6.81 to 5.88; p = 0.88; I 2 = 84%). No significant difference was found comparing the patients with treatment-related adverse events. The relationship was robust in sensitivity analysis and consistent in most of the subgroup analyses. As to the primary outcomes (WOMAC pain, function scores, VAS for pain), the difference between hylan and HA did not reach the previously reported minimum clinically important difference (MCID) values (–13.4 for VAS for pain, –2.0 for WOMAC pain score, –7.7 for WOMAC function score). Our meta-analysis showed that there were no statistically and clinically significant differences in pain relief and function improvement between hylan and HA injections for knee OA treatment. In view of its higher costs, we discourage the use of hylan in patients with knee OA in clinical practice. The level of evidence is I, meta-analysis of Level I studies.

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Acupotomy Therapy for Knee Osteoarthritis Pain: Systematic Review and Meta-Analysis

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/2168283 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Jigao Sun ◽

Yan Zhao ◽

Ruizheng Zhu ◽

Qianglong Chen ◽

Mengge Song ◽

...

Keyword(s):

Systematic Review ◽

Knee Osteoarthritis ◽

Pain Score ◽

Meta Analysis ◽

Cochrane Library ◽

Womac Pain ◽

Womac Pain Score ◽

Knee Oa ◽

Effectiveness Rate ◽

And Function

Background and Purpose. Knee osteoarthritis (OA) is a major public health problem, and currently, few effective medical treatments exist. Chinese acupotomy therapy has been widely used for the treatment of knee OA in China. We conducted this systematic review and meta-analysis to evaluate the efficacy of Chinese acupotomy in treating knee OA to inform clinical practice. Methods. We performed a comprehensive search on PubMed, the Cochrane Library, EMBASE, and four Chinese databases for articles published prior to June 2020. We included only randomized controlled trials (RCTs) that used acupotomy therapy as the major intervention in adults with knee OA, were published in either Chinese and English, included more than 20 subjects in each group, and included pain and function in the outcome measures. Knee OA was defined by the American College of Rheumatology or Chinese Orthopedic Association criteria in all studies. We extracted the visual analogue scale (VAS) pain score, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score, the total effectiveness rate, the modified Japanese Orthopedic Association (JOA) activities of daily living score, and Lysholm’s score. We calculated the mean difference (MD) or risk ratio (RR) for all relevant outcomes. Meta-analyses were conducted using random-effects models when appropriate. Results. We identified 1317 potentially relevant studies, thirty-two of which met the eligibility criteria and were conducted in China between 2007 and 2020. A total of 3021 knee OA patients (62.96% female, median age: 57 years, and median disease duration: 33 months) were included. The treatment duration ranged from 1 week to 5 weeks (median: 3 weeks). The typical acupotomy treatment involved releasing soft tissue adhesions and was performed once a week for 1–5 weeks until the pain was relieved. The control group treatments included acupuncture (8 studies), electroacupuncture (10 studies), sodium hyaluronate (8 studies), radiofrequency electrotherapy (1 study), and nonsteroidal anti-inflammatory drugs (NSAIDs, 5 studies). The results from the meta-analysis showed that acupotomy led to superior improvements in the VAS pain score (MD = −1.11; 95% confidence interval (CI), −1.51 to −0.71; p < 0.00001) and WOMAC pain score (MD = −2.32; 95% CI, −2.94 to −1.69; p < 0.00001), a higher total effectiveness rate (RR = 1.15; 95% CI, 1.09–1.21; p < 0.00001), and superior improvements in the JOA score (MD = 6.39; 95% CI, 4.11–9.76; p < 0.00001) and Lysholm’s score (MD = 12.75; 95% CI, 2.61–22.89; p = 0.01) for overall pain and function. No serious adverse events were reported. Conclusion. Chinese acupotomy therapy may relieve pain and improve function in patients with knee OA. Furthermore, rigorously designed and well-controlled RCTs are warranted.

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An international, multicentre, double-blind, randomized study (DISSCO): effect of diacerein vs celecoxib on symptoms in knee osteoarthritis

Rheumatology ◽

10.1093/rheumatology/keaa072 ◽

2020 ◽

Vol 59 (12) ◽

pp. 3858-3868

Author(s):

Jean-Pierre Pelletier ◽

Jean-Pierre Raynauld ◽

Marc Dorais ◽

Louis Bessette ◽

Eva Dokoupilova ◽

...

Keyword(s):

Pain Score ◽

Phase Iii ◽

Comparable Efficacy ◽

Womac Pain ◽

Double Blind ◽

Once Daily ◽

Womac Pain Score ◽

Knee Oa ◽

Symptomatic Knee ◽

Significant Difference

Abstract Objective The objective of this study was to investigate whether diacerein has comparable efficacy with celecoxib in pain reduction for treatment in symptomatic knee OA patients. Methods This randomized double-blind multicentre non-inferiority trial evaluated diacerein vs celecoxib treatment in patients with Kellgren–Lawrence grade 2–3 and pain scoring ≥4 (10-cm VAS). Patients were randomized to 6 months of treatment with diacerein 50 mg (n = 187) once daily for 1 month and twice daily thereafter, or celecoxib 200 mg (n = 193) once daily. The primary outcome was the change in WOMAC pain score (0–50 cm) at 6 months, and the secondary outcomes were WOMAC sub-scores, VAS pain score, and the OMERACT–OARSI responder rate. Results In the per protocol population, the adjusted mean change from baseline in the WOMAC pain score was –11.1 ( 0.9) with diacerein (n = 140) and –11.8 (0.9) with celecoxib (n = 148). The intergroup difference was 0.7 (95% CI: −1.8, 3.2; P = 0.597), meeting the non-inferiority margin. Supportive analysis of the intention-to-treat population gave similar results. Other outcomes showed no significant difference between treatment groups. The incidence of treatment-related adverse events was low and balanced between groups, but a greater incidence of diarrhoea occurred with diacerein (10.2% vs 3.7%). Diarrhoea was considered mild-to-moderate in all but one case with complete resolution. Conclusions Diacerein was non-inferior to celecoxib in reducing knee OA pain and improving physical function. Diacerein also demonstrated a good safety profile. Trial registration A multicentre study on the effect of DIacerein on Structure and Symptoms vs Celecoxib in Osteoarthritis is a National Institutes of Health (NCT02688400) and European Clinical Trial Database (2015–002933-23) registered phase III (Canada) or IV (Europe) study.

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