Osteoarthritis (OA) is a complex heterogeneous articular disease with multiple joint tissue involvement of varying severity and no regulatory-agency-approved diseasemodifying drugs (DMOADs). In this review, we discuss the reasons necessitating the development of DMOADs for OA management, the classifications of clinical phenotypes or molecular/mechanistic endotypes from the viewpoint of targeted drug discovery, and then summarize the efficacy and safety profile of a range of targeted drugs in Phase 2 and 3 clinical trials directed to cartilage-driven, bone-driven, and inflammation-driven endotypes. Finally, we briefly put forward the reasons for failures in OA clinical trials and possible steps to overcome these barriers.

IMPORTANCE Most clinical guidelines do not recommend platelet-rich plasma (PRP) for knee osteoarthritis (OA) because of lack of high-quality evidence on efficacy for symptoms and joint structure, but the guidelines emphasize the need for rigorous studies. Despite this, use of PRP in knee OA is increasing.OBJECTIVE To evaluate the effects of intra-articular PRP injections on symptoms and joint structure in patients with symptomatic mild to moderate radiographic medial knee OA.DESIGN, SETTING, AND PARTICIPANTS This randomized, 2-group, placebo-controlled, participant-, injector-, and assessor-blinded clinical trial enrolled community-based participants (n = 288) aged 50 years or older with symptomatic medial knee OA (Kellgren and Lawrence grade 2 or 3) in Sydney and Melbourne, Australia, from August 24, 2017, to July 5, 2019. The 12-month follow-up was completed on July 22, 2020.INTERVENTIONS Interventions involved 3 intra-articular injections at weekly intervals of either leukocyte-poor PRP using a commercially available product (n = 144 participants) or saline placebo (n = 144 participants). MAIN OUTCOMES AND MEASURESThe 2 primary outcomes were 12-month change in overall average knee pain scores (11-point scale; range, 0-10, with higher scores indicating worse pain; minimum clinically important difference of 1.8) and percentage change in medial tibial cartilage volume as assessed by magnetic resonance imaging (MRI). Thirty-one secondary outcomes (25 symptom related and 6 MRI assessed; minimum clinically important difference not known) evaluated pain, function, quality of life, global change, and joint structures at 2-month and/or 12-month follow-up. RESULTS Among 288 patients who were randomized (mean age, 61.9 [SD, 6.5] years; 169 [59%] women), 269 (93%) completed the trial. In both groups, 140 participants (97%) received all 3 injections. After 12 months, treatment with PRP vs placebo injection resulted in a mean change in knee pain scores of −2.1 vs −1.8 points, respectively (difference, −0.4 [95% CI, −0.9 to 0.2] points; P = .17). The mean change in medial tibial cartilage volume was −1.4% vs −1.2%, respectively (difference, −0.2% [95% CI, −1.9% to 1.5%]; P = .81). Of 31 prespecified secondary outcomes, 29 showed no significant between-group differences.CONCLUSIONS AND RELEVANCE Among patients with symptomatic mild to moderate radiographic knee OA, intra-articular injection of PRP, compared with injection of saline placebo, did not result in a significant difference in symptoms or joint structure at 12 months. These findings do not support use of PRP for the management of knee OA.

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Ultrasound has become popular among rheumatologists as the first-choice imaging investigation for the evaluation and monitoring of osteoarthritis (OA). Because of recent improvement in technology, ultrasound has the ability to demonstrate and assess the minimal structural abnormalities, which involve the pathophysiology and progression of OA, such as articular cartilage, synovial tissue, bony cortex, and other soft tissue. Nowadays, ultrasonography is a promising technique for assessing soft tissue abnormalities such as joint effusion, synovial hypertrophy, Baker cyst, and other structural changes including the decrease in cartilage thickness, meniscus bulging, and formation of osteophyte. Ultrasonography not only possesses diagnostic potential in knee OA but also reveals long-term predictability for disease progress as imaging biomarker. Ultrasonography has also been proven as a useful tool in guiding therapeutic interventions and monitoring treatment effectiveness. This review addresses the utility, reliability, and potential utilization of ultrasonography as an imaging technique in knee OA.

Background Thumb-base osteoarthritis (OA) is a common cause of pain and disability This study aimed to investigate the associations of musculoskeletal ultrasound OA pathologies with the extent of pain, function, radiographic scores, and muscle strength in symptomatic thumb-base osteoarthritis. Methods This is a cross-sectional study of an ongoing clinical trial with eligibility criteria including thumb-base pain on Visual Analogue Scale (VAS) ≥40 (0 to 100 mm), Functional Index for Hand OA (FIHOA) ≥ 6 (0 to 30) and Kellgren Lawrence (KL) grade ≥ 2. The most symptomatic side was scanned to measure synovitis and osteophyte severity using a 0–3 semi-quantitative score, power Doppler and erosion in binary score. A linear regression model was used for associations of ultrasound findings with VAS pain, FIHOA and hand grip and pinch strength tests after adjusting for age, gender, body mass index, disease duration and KL grade as appropriate. For correlation of ultrasound features with KL grade, OARSI ((Osteoarthritis Research Society International) osteophyte and JSN scores, Eaton grades, Spearman coefficients were calculated, and a significant test defined as a p -value less than 0.05. Results The study included 93 participants (mean age of 67.04 years, 78.5% females). Presence of power Doppler has a significant association with VAS pain [adjusted β coefficient = 11.29, P = 0.02] while other ultrasound pathologies revealed no significant associations with all clinical outcomes. In comparison to radiograph, ultrasonographic osteophyte score was significantly associated with KL grade [r s = 0.44 ( P < 0.001)], OARSI osteophyte grade [r s = 0.35 ( P = 0.001)], OARSI JSN grade [r s = 0.43 (P < 0.001)] and Eaton grade [r s = 0.30 ( P < 0.01)]. Ultrasonographic erosion was significantly related with radiographic erosion [r s = − 0.49 (P = 0.001)]. Conclusion From a clinical perspective the significant relationship of power Doppler with pain severity in thumb base OA suggests this might be a useful tool in understanding pain aetiology. It is important to recognise that power Doppler activity was only detected in 14% of the study so this might be an important subgroup of persons to monitor more closely. Trial registration Registered at Australian New Zealand Clinical Trials Registry (ANZCTR), http://www.anzctr.org.au/ , ACTRN12616000353493.

CRD42016039954.

Objective To investigate the associations of Outcome Measures in Rheumatology (OMERACT) ultrasound scores for knee osteoarthritis (OA) with pain severity, other symptoms, and OA severity on radiographs and magnetic resonance imaging (MRI). Methods Participants with symptomatic and mild-moderate radiographic knee OA underwent baseline dynamic ultrasound assessment according to standardized OMERACT scanning protocol. Using the published ultrasound image atlas, a physician operator obtained semi-quantitative or binary scores for ultrasound pathologies. Clinical severity was measured on Numerical Rating Score (NRS) and Knee Injury and Osteoarthritis Outcome Score (KOOS) symptoms and pain sub-scores. OA severity was assessed using the Kellgren-Lawrence grade (KLG) on X-rays and MRI osteoarthritis knee score (MOAKS) on non-contrast-enhanced MRI. Separate linear regression models were used to determine associations of ultrasound OA pathologies with pain and KOOS sub-scores, and Spearman’s correlations were used for ultrasound scores with KLG and MOAKS. Results Eighty-nine participants were included. Greater synovial hypertrophy, power Doppler (PD) and meniscal extrusion scores were associated with worse NRS pain (B=0.92,95% confidence interval CI 0.25,1.58); B=0.73(95% CI 0.11,1.35) and B=1.01(95% CI 0.22,1.80). All greater ultrasound scores except for cartilage grade demonstrated significant associations with worse KOOS symptoms while only PD and meniscal extrusion were associated with worse KOOS pain. All ultrasound scores except for PD were significantly correlated with KLG. Ultrasound pathologies except for cartilage revealed moderate to good correlation with their MOAKS counterparts with ultrasound synovitis having the greatest correlation {0.69(95% CI 0.60, 0.78}. Conclusion OMERACT ultrasound scores revealed significant associations with pain severity, KLG and MOAKS.

IntroductionManagement of thumb base osteoarthritis (OA) using a combination of therapies is common in clinical practice; however, evidence for the efficacy of this approach is lacking. The aim of this study is to determine the effect of a combination of conservative therapies for the treatment of thumb base OA compared with an education control group.Methods and analysisThis is a randomised, controlled, single-centre, two-arm superiority trial with 1:1 allocation ratio; with assessor and statistician blinded. Participants are blinded to the trial's hypothesis and to the interventions received by the opposite group. A total of 204 participants will be recruited from the community and randomised using a computer-generated schedule. The intervention group will receive education for joint protection and OA, a splint for the base of the thumb, hand exercises and topical diclofenac sodium 1% gel over 6 weeks. The control group will receive education for joint protection and OA alone. Main inclusion criteria are pain ≥40 mm (Visual Analogue Scale, 0–100) at the base of the thumb, impairment in hand function ≥6 (Functional Index for Hand Osteoarthritis, 0–30) and radiographic thumb base OA (Kellgren Lawrence grade ≥2). Participants currently receiving any of the intervention components will be excluded. Outcomes will be measured at 2, 6 and 12 weeks. The primary outcome is change in pain and hand function from baseline to 6 weeks. Other outcomes include changes in grip and pinch strength, quality of life, presence of joint swelling and tenderness, duration of joint stiffness, patient's global assessment and use of rescue medication. Analysis will be performed according to the intention-to-treat principle. Adverse events will be monitored throughout the study.Ethics and disseminationThis protocol is approved by the local ethics committee (HREC/15/HAWKE/479). Dissemination will occur through presentations at international conferences and publication in peer-reviewed journals.Trial registration numberACTRN12616000353493; Pre-results.