Aim
Intra‐articular corticosteroid injections (IACIs) can reduce osteoarthritis‐related pain, with differing levels of response across patient groups. This systematic review investigates what is ...known about the positive and negative predictors of outcomes in patients with osteoarthritis who undergo IACIs.
Methods
We systematically searched the Medline, Embase, and Cochrane databases to May 2023 for studies that evaluated patients undergoing IACIs for osteoarthritis and reported on predictors of outcomes in these patients.
Results
Eight studies were included. Two were placebo‐controlled trials, six were observational studies. Due to the heterogeneity of outcomes and variables between the studies, it was not possible to pool the results for formal meta‐analysis. Higher baseline pain, older age, higher BMI, lower range of movement, higher Kellgren‐Lawrence radiographic score, joint effusion, and aspiration were shown to be predictors of a positive response to IACIs in some of the included studies. However, other studies showed no difference in response with these variables, or a negative correlation with response. Sex, smoking, mental health status, hypertension/ischaemic heart disease, diabetes mellitus, duration of symptoms, and socioeconomic status did not demonstrate any correlation with the prediction of positive or negative outcomes after IACIs.
Conclusion
Several patient features have been identified as positive predictors of outcomes following IACIs. However, this systematic review has identified inconsistent and variable findings across the existing literature. Further research with standardization of IACI administration and outcome measures is required to facilitate further analysis of the reliability and significance of predictive factors for response to IACIs.
Objective
To update the 2009 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) treatment recommendations for the spectrum of manifestations affecting patients with ...psoriatic arthritis (PsA).
Methods
GRAPPA rheumatologists, dermatologists, and PsA patients drafted overarching principles for the management of PsA, based on consensus achieved at face‐to‐face meetings and via online surveys. We conducted literature reviews regarding treatment for the key domains of PsA (arthritis, spondylitis, enthesitis, dactylitis, skin disease, and nail disease) and convened a new group to identify pertinent comorbidities and their effect on treatment. Finally, we drafted treatment recommendations for each of the clinical manifestations and assessed the level of agreement for the overarching principles and treatment recommendations among GRAPPA members, using an online questionnaire.
Results
Six overarching principles had ≥80% agreement among both health care professionals (n = 135) and patient research partners (n = 10). We developed treatment recommendations and a schema incorporating these principles for arthritis, spondylitis, enthesitis, dactylitis, skin disease, nail disease, and comorbidities in the setting of PsA, using the Grading of Recommendations, Assessment, Development and Evaluation process. Agreement of >80% was reached for approval of the individual recommendations and the overall schema.
Conclusion
We present overarching principles and updated treatment recommendations for the key manifestations of PsA, including related comorbidities, based on a literature review and consensus of GRAPPA members (rheumatologists, dermatologists, other health care providers, and patient research partners). Further updates are anticipated as the therapeutic landscape in PsA evolves.
Management of Osteoarthritis of the Knee (nonarthroplasty) Evidence-Based Clinical Practice Guideline is based on a systematic review of published studies for the nonarthroplasty treatment of ...osteoarthritis of the knee in adults (ages 17 years and older). The purpose of this clinical practice guideline is to evaluate current best evidence associated with treatment. The scope of this guideline contains nonpharmacologic and pharmacologic interventions for symptomatic osteoarthritis of the knee, including surgical procedures less invasive than knee arthroplasty. It does not provide recommendations for patients with rheumatoid arthritis, arthritis of other joints, or other imflammatory athropathies. This guideline contains 29 recommendations to assist all qualified and appropriately trained healthcare professionals involved in the nonarthroplasty management of osteoarthritis of the knee and provide information for patients. In addition, the work group highlighted the need for better research into intra-articular corticosteroid, hyaluronic acid, and platelet-rich plasma detailing osteoarthritis characterization, including subgroup analyses and osteoarthrosis severity stratification, and clinically relevant outcomes with control subjects for bias and cost-effectiveness analysis. Studies comparing outcomes in patients with mild-to-moderate knee osteoarthritis and an MRI confirmed meniscal tear who have undergone partial meniscectomy after failing to improve with a course of conservative treatment (nonsteroidal anti-inflammatory drugs, steroid injection, and physical therapy) versus those who have undergone partial meniscectomy without a dedicated course of conservative treatment. Prospective randomized trials or prospective cohort studies are still needed to establish efficacy of individual oral nonsteroidal anti-inflammatory drugs within specific subgroups and populations to tailor systemic medications to help increase efficacy and decrease the risk of adverse effects.
Purpose The aims of this study were (1) to perform a systematic review of meta-analyses evaluating platelet-rich plasma (PRP) injection in the treatment of knee joint cartilage degenerative ...pathology, (2) to provide a framework for analysis and interpretation of the best available evidence to provide recommendations for use (or lack thereof) of PRP in the setting of knee osteoarthritis (OA), and (3) to identify literature gaps where continued investigation would be suggested. Methods Literature searches were performed for meta-analyses examining use of PRP versus corticosteroids, hyaluronic acid, oral nonsteroidal anti-inflammatory drugs, or placebo. Clinical data were extracted, and meta-analysis quality was assessed. The Jadad algorithm was applied to determine meta-analyses that provided the highest level of evidence. Results Three meta-analyses met the eligibility criteria and ranged in quality from Level II to Level IV evidence. All studies compared outcomes of treatment with intra-articular platelet-rich plasma (IA-PRP) versus control (intra-articular hyaluronic acid or intra-articular placebo). Use of PRP led to significant improvements in patient outcomes at 6 months after injection, and these improvements were seen starting at 2 months and were maintained for up to 12 months. It is unclear if the use of multiple PRP injections, the double-spinning technique, or activating agents leads to better outcomes. Patients with less radiographic evidence of arthritis benefit more from PRP treatment. The use of multiple PRP injections may increase the risk of self-limited local adverse reactions. After application of the Jadad algorithm, 3 concordant high-quality meta-analyses were selected and all showed that IA-PRP provided clinically relevant improvements in pain and function compared with the control treatment. Conclusions IA-PRP is a viable treatment for knee OA and has the potential to lead to symptomatic relief for up to 12 months. There appears to be an increased risk of local adverse reactions after multiple PRP injections. IA-PRP offers better symptomatic relief to patients with early knee degenerative changes, and its use should be considered in patients with knee OA. Level of Evidence Level IV, systematic review of Level II through IV studies.
Stem cell injection for knee osteoarthritis (KOA) is an emerging new therapy, and we aimed to review its evidence of efficacy.
Systematic review.
Criteria for eligibility were randomised controlled ...trials (RCTs) and non-RCT on the efficacy of stem cell injections in KOA. All references were checked for missed articles.
MEDLINE, EMBASE, CINAHL, Web of Science, Cochrane Library, PEDro and SPORTDiscus were searched. A grey literature search was performed. No restrictions were imposed to our search strategy.
Risk of bias was assessed using the Cochrane risk of bias tool. Descriptive synthesis was performed using the levels of evidence according to the Oxford Levels of Evidence.
Five RCTs and one non-RCT were found. Bone-marrow-derived stem cells, adipose-derived mesenchymal stem cells and peripheral blood stem cells were used. All trials were at high risk of bias, resulting in level-3 evidence. All five RCTs reported superior efficacy for patient-reported outcomes (Visual Analogue Scale, Western Ontario and McMaster Universities Arthritis Index, Tegner, Lysolm, International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, Lequesne) compared with controls at final follow-up (range 24-48 months). Superior radiological outcomes were found favouring stem cell injection. Superior histological outcomes and/or improved arthroscopically scored healing rates were reported in two trials. No serious adverse events were reported.
Six trials with high risk of bias showed level-3 or level-4 evidence in favour of stem cell injections in KOA. In the absence of high-level evidence, we do not recommend stem cell therapy for KOA.
IMPORTANCE: Osteoarthritis (OA) is the most common joint disease, affecting an estimated more than 240 million people worldwide, including an estimated more than 32 million in the US. Osteoarthritis ...is the most frequent reason for activity limitation in adults. This Review focuses on hip and knee OA. OBSERVATIONS: Osteoarthritis can involve almost any joint but typically affects the hands, knees, hips, and feet. It is characterized by pathologic changes in cartilage, bone, synovium, ligament, muscle, and periarticular fat, leading to joint dysfunction, pain, stiffness, functional limitation, and loss of valued activities, such as walking for exercise and dancing. Risk factors include age (33% of individuals older than 75 years have symptomatic and radiographic knee OA), female sex, obesity, genetics, and major joint injury. Persons with OA have more comorbidities and are more sedentary than those without OA. The reduced physical activity leads to a 20% higher age-adjusted mortality. Several physical examination findings are useful diagnostically, including bony enlargement in knee OA and pain elicited with internal hip rotation in hip OA. Radiographic indicators include marginal osteophytes and joint space narrowing. The cornerstones of OA management include exercises, weight loss if appropriate, and education—complemented by topical or oral nonsteroidal anti-inflammatory drugs (NSAIDs) in those without contraindications. Intra-articular steroid injections provide short-term pain relief and duloxetine has demonstrated efficacy. Opiates should be avoided. Clinical trials have shown promising results for compounds that arrest structural progression (eg, cathepsin K inhibitors, Wnt inhibitors, anabolic growth factors) or reduce OA pain (eg, nerve growth factor inhibitors). Persons with advanced symptoms and structural damage are candidates for total joint replacement. Racial and ethnic disparities persist in the use and outcomes of joint replacement. CONCLUSIONS AND RELEVANCE: Hip and knee OA are highly prevalent and disabling. Education, exercise and weight loss are cornerstones of management, complemented by NSAIDs (for patients who are candidates), corticosteroid injections, and several adjunctive medications. For persons with advanced symptoms and structural damage, total joint replacement effectively relieves pain.
•Precision medicine is necessary to treat multiple facets of osteoarthritis.•Disease-modifying osteoarthritis drugs (DMOADs) and drug delivery systems (DDSs) are discussed.•DMOADs should be combined ...with adequate DDSs for long-term intra-articular (IA) therapy.•Clinical trials of small molecules delivered by IA injections are summarized.•Hydrogels, liposomes, nanoparticles and microparticles are reviewed.
Osteoarthritis (OA) is the most common degenerative disease of the joint. Despite many reports and numerous clinical trials, OA is not entirely understood, and there is no effective treatment available for this disease. To satisfy this unmet medical need, drug delivery systems (DDSs) containing disease-modifying OA drugs (DMOADs) for intra-articular (IA) administration are required to improve the health of OA patients. DDSs should provide controlled and/or sustained drug release, enabling long-term treatment with a reduced number of injections. This paper reviews the role and interaction among different tissues involved in OA and summarizes recent clinical trials and research on DDSs, focusing on small-molecule delivery. To achieve an ideal treatment, various key criteria have been identified to design and develop an IA DDS matching the clinical needs.
Optimized intra-articularly administered drug delivery systems associated with potent disease-modifying osteoarthritis drugs that can stop and/or reverse osteoarthritis evolution represent a promising approach for effective therapy.
Intra-articular drug delivery has a number of advantages over systemic administration; however, for the past 20 years, intra-articular treatment options for the management of knee osteoarthritis (OA) ...have been limited to analgesics, glucocorticoids, hyaluronic acid (HA) and a small number of unproven alternative therapies. Although HA and glucocorticoids can provide clinically meaningful benefits to an appreciable number of patients, emerging evidence indicates that the apparent effectiveness of these treatments is largely a result of other factors, including the placebo effect. Biologic drugs that target inflammatory processes are used to manage rheumatoid arthritis, but have not translated well into use in OA. A lack of high-level evidence and methodological limitations hinder our understanding of so-called 'stem' cell therapies and, although the off-label administration of intra-articular cell therapies (such as platelet-rich plasma and bone marrow aspirate concentrate) is common, high-quality clinical data are needed before these treatments can be recommended. A number of promising intra-articular treatments are currently in clinical development in the United States, including small-molecule and biologic therapies, devices and gene therapies. Although the prospect of new, non-surgical treatments for OA is exciting, the benefits of new treatments must be carefully weighed against their costs and potential risks.
Background
Osteoarthritis (OA) is the most prevalent chronic joint disorder worldwide and is associated with significant pain and disability.
Objectives
To assess the effects of viscosupplementation ...in the treatment of OA of the knee. The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz (Artzal, Supartz), BioHy (Arthrease, Euflexxa, Nuflexxa), Durolane, Fermathron, Go‐On, Hyalgan, Hylan G‐F 20 (Synvisc Hylan G‐F 20), Hyruan, NRD‐101 (Suvenyl), Orthovisc, Ostenil, Replasyn, SLM‐10, Suplasyn, Synject and Zeel compositum).
Search methods
MEDLINE (up to January (week 1) 2006 for update), EMBASE, PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Specialised journals and reference lists of identified randomised controlled trials (RCTs) and pertinent review articles up to December 2005 were handsearched.
Selection criteria
RCTs of viscosupplementation for the treatment of people with a diagnosis of OA of the knee were eligible. Single and double‐blinded studies, placebo‐based and comparative studies were eligible. At least one of the four OMERACT III core set outcome measures had to be reported (Bellamy 1997).
Data collection and analysis
Each trial was assessed independently by two reviewers for its methodological quality using a validated tool. All data were extracted by one reviewer and verified by a second reviewer . Continuous outcome measures were analysed as weighted mean differences (WMD) with 95% confidence intervals (CI). However, where different scales were used to measure the same outcome, standardized mean differences (SMD) were used. Dichotomous outcomes were analyzed by relative risk (RR).
Main results
Seventy‐six trials with a median quality score of 3 (range 1 to 5) were identified. Follow‐up periods varied between day of last injection and eighteen months. Forty trials included comparisons of hyaluronan/hylan and placebo (saline or arthrocentesis), ten trials included comparisons of intra‐articular (IA) corticosteroids, six trials included comparisons of nonsteroidal anti‐inflammatory drugs (NSAIDs), three trials included comparisons of physical therapy, two trials included comparisons of exercise, two trials included comparisons of arthroscopy, two trials included comparisons of conventional treatment, and fifteen trials included comparisons of other hyaluronans/hylan. The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 28 to 54% for pain and 9 to 32% for function. In general, comparable efficacy was noted against NSAIDs and longer‐term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses.
Authors' conclusions
Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head‐to‐head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect‐size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection.
In general, sample‐size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events.
In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.
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