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Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis.

ABSTRACT: Importance:Even though osteoarthritis is a chronic and progressive disease, pharmacological agents are mainly studied over short-term periods, resulting in unclear recommendations for long-term disease management. Objective:To search, review, and analyze long-term (?12 months) outcomes (symptoms, joint structure) from randomized clinical trials (RCTs) of medications for knee osteoarthritis. Data Sources and Study Selection:The databases of MEDLINE, Scopus, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched until June 30, 2018 (MEDLINE alerts through August 31, 2018) for RCTs of patients with knee osteoarthritis that had treatment and follow-up lasting 1 year or longer. Data Extraction and Synthesis:Data at baseline and at the longest available treatment and follow-up of 12 months' duration or longer (or the change from baseline) were extracted. A Bayesian random-effects network meta-analysis was performed. Main Outcomes and Measures:The primary outcome was the mean change from baseline in knee pain. Secondary outcomes were physical function and joint structure (the latter was measured radiologically as joint space narrowing). Standardized mean differences (SMDs) and mean differences with 95% credibility intervals (95% CrIs) were calculated. Findings were interpreted as associations when the 95% CrIs excluded the null value. Results:Forty-seven RCTs (22?037 patients; mean age range, mostly 55-70 years; and a higher mean proportion of women than men, around 70%) included the following medication categories: analgesics; antioxidants; bone-acting agents such as bisphosphonates and strontium ranelate; nonsteroidal anti-inflammatory drugs; intra-articular injection medications such as hyaluronic acid and corticosteroids; symptomatic slow-acting drugs in osteoarthritis such as glucosamine and chondroitin sulfate; and putative disease-modifying agents such as cindunistat and sprifermin. Thirty-one interventions were studied for pain, 13 for physical function, and 16 for joint structure. Trial duration ranged from 1 to 4 years. Associations with decreases in pain were found for the nonsteroidal anti-inflammatory drug celecoxib (SMD, -0.18 [95% CrI, -0.35 to -0.01]) and the symptomatic slow-acting drug in osteoarthritis glucosamine sulfate (SMD, -0.29 [95% CrI, -0.49 to -0.09]), but there was large uncertainty for all estimates vs placebo. The association with pain improvement remained significant only for glucosamine sulfate when data were analyzed using the mean difference on a scale from 0 to 100 and when trials at high risk of bias were excluded. Associations with improvement in joint space narrowing were found for glucosamine sulfate (SMD, -0.42 [95% CrI, -0.65 to -0.19]), chondroitin sulfate (SMD, -0.20 [95% CrI, -0.31 to -0.07]), and strontium ranelate (SMD, -0.20 [95% CrI, -0.36 to -0.05]). Conclusions and Relevance:In this systematic review and network meta-analysis of studies of patients with knee osteoarthritis and at least 12 months of follow-up, there was uncertainty around the estimates of effect size for change in pain for all comparisons with placebo. Larger RCTs are needed to resolve the uncertainty around efficacy of medications for knee osteoarthritis.

SUBMITTER: Gregori D

PROVIDER: S-EPMC6583519 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis.

Gregori Dario D Giacovelli Giampaolo G Minto Clara C Barbetta Beatrice B Gualtieri Francesca F Azzolina Danila D Vaghi Paola P Rovati Lucio C LC

JAMA 20181201 24

<h4>Importance</h4>Even though osteoarthritis is a chronic and progressive disease, pharmacological agents are mainly studied over short-term periods, resulting in unclear recommendations for long-term disease management.<h4>Objective</h4>To search, review, and analyze long-term (≥12 months) outcomes (symptoms, joint structure) from randomized clinical trials (RCTs) of medications for knee osteoarthritis.<h4>Data sources and study selection</h4>The databases of MEDLINE, Scopus, EMBASE, Web of Sc ...[more]

PMID: 30575881

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Project description:MethodsWe 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.ResultsWe 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.ConclusionChinese acupotomy therapy may relieve pain and improve function in patients with knee OA. Furthermore, rigorously designed and well-controlled RCTs are warranted.

Project description:BackgroundThere is no cure for knee osteoarthritis (KOA) and typically patients live approximately 30-years with the disease. Most common medical treatments result in short-term palliation of symptoms with little consideration of long-term risk. This systematic review aims to appraise the current evidence for the long-term (≥12 months) safety of common treatments for knee osteoarthritis (KOA).MethodsCochrane Database of Systematic Reviews, Medline and PubMed were systematically searched from 1990 to July 2017, inclusive. Inclusion criteria were 1) peer-reviewed publications investigating treatments for KOA referred to in the Australian Clinical Care Standard and/or Therapeutic Guidelines: Rheumatology 2) specifically addressing safety of the treatments 3) with ≥12 months of follow-up and 4) Downs and Black quality score ≥ 13.ResultsThirty-four studies fulfilled the inclusion criteria. Lifestyle modifications (moderate exercise and weight loss), paracetamol, glucosamine, Intraarticular Hyaluronic Acid (IAHA) and platelet-rich-plasma (PRP) injections have a low risk of harm and beneficial ≥12 month outcomes. Although Nonsteroidal Anti-inflammatory Drugs (NSAIDs) provide pain relief, they are associated with increased risk of medical complications. Cortisone injections are associated with radiological cartilage degeneration at > 12 months. Arthroscopy for degenerative meniscal tears in KOA leads to a 3-fold increase in total knee arthroplasty (TKA). TKA improves primary outcomes of KOA but has a low rate of significant medical complications.ConclusionsGiven the safety and effectiveness of lifestyle interventions such as weight loss and exercise, these should be advocated in all patients due to the low risk of harm. The use of NSAIDs should be minimized to avoid gastrointestinal complications. Treatment with opioids has a lack of evidence for use and a high risk of long-term harm. The use of IAHA and PRP may provide additional symptomatic benefit without the risk of harm. TKA is associated with significant medical complications but is justified by the efficacy of joint replacement in late-stage disease.Trial registrationPROSPERO International prospective register for systematic reviews; registration number CRD42017072809 .

Project description:BackgroundWith the continuous development of clinical medicine, an increasing number of non-pharmacological interventions have been applied for the treatment of knee osteoarthritis (KOA), with the results of several recent randomized controlled trials (RCTs) showing that a variety of externally-applied, non-pharmacological interventions (EANPI) can improve symptoms and inflammation in patients with KOA. However, the relative benefits and disadvantages of non-drug therapies remain uncertain, and an optimal treatment strategy has not yet been determined.ObjectiveThis study applied network meta-analysis (NMA) to compare and rank the effectiveness of EANPI on the short- and long-term clinical symptoms and inflammatory cytokine levels in patients with KOA.MethodsTwo independent researchers searched online databases and performed manual retrieval of related citations to identify RCTs that met the selection criteria for the network meta-analysis. These researchers retrieved studies indexed from database inception to August 2023 and performed data extraction and assessment of the risk of bias.ResultsThe analysis included 80 RCTs involving 8440 participants and nine externally-applied, non-pharmacological therapies, namely extracorporeal shock wave, radiofrequency, acupotomy, laser therapy, Tuina therapy, kinesio taping, electroacupuncture, platelet-rich plasma injection, and ozone therapy. The treatment courses ranged from 1 to 12 weeks, with follow-up periods ranging from 4 to 24 weeks. The results of the NMA indicated that each non-drug therapy was superior to sham intervention in improving all outcome indicators. Except for the visual analog scale (VAS) and Western Ontario MacMaster (WOMAC) pain outcomes, all non-drug therapies had better efficacy than pharmacological treatments. For short-term VAS and tumor necrosis factor-alpha (TNF-α), extracorporeal shock wave performed better than other therapies (90.2% and 85.2% respectively). Radiofrequency therapy may be the most promising method to reduce long-term VAS, short- and long-term WOMAC pain, and interleukin (IL)-1β level (84.8%, 97.8%, 90.1%, 94.8% respectively). Tuina therapy may be a significant choice for short- and long-term outcomes of WOMAC function and range of motion (ROM).ConclusionsThe results of the comprehensive comparison of the outcome indicators in 9 different EANPI indicated that radiofrequency and Tuina therapy were more effective and consistently ranked high in improving clinical symptoms in the short and long term. Radiofrequency is effective at relieving pain, and Tuina therapy can be given priority for treatment when hypofunction is the main symptom. EANPI to improve pain symptoms may be related to the regulation of inflammatory cytokine levels, which may be a potential mechanism of action.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42023464177.

Project description:Surgical pain is managed with multi-modal anaesthesia in total hip replacement (THR) and total knee replacement (TKR). It is unclear whether including local anaesthetic infiltration before wound closure provides additional pain control.We performed a systematic review of randomised controlled trials of local anaesthetic infiltration in patients receiving THR or TKR. We searched MEDLINE, Embase and Cochrane CENTRAL to December 2012. Two reviewers screened abstracts, extracted data, and contacted authors for unpublished outcomes and data. Outcomes collected were post-operative pain at rest and during activity after 24 and 48 hours, opioid requirement, mobilisation, hospital stay and complications. When feasible, we estimated pooled treatment effects using random effects meta-analyses.In 13 studies including 909 patients undergoing THR, patients receiving local anaesthetic infiltration experienced a greater reduction in pain at 24 hours at rest by standardised mean difference (SMD) -0.61 (95% CI -1.05, -0.16; p = 0.008) and by SMD -0.43 (95% CI -0.78 -0.09; p = 0.014) at 48 hours during activity.In TKR, diverse multi-modal regimens were reported. In 23 studies including 1439 patients undergoing TKR, local anaesthetic infiltration reduced pain on average by SMD -0.40 (95% CI -0.58, -0.22; p < 0.001) at 24 hours at rest and by SMD -0.27 (95% CI -0.50, -0.05; p = 0.018) at 48 hours during activity, compared with patients receiving no infiltration or placebo. There was evidence of a larger reduction in studies delivering additional local anaesthetic after wound closure. There was no evidence of pain control additional to that provided by femoral nerve block.Patients receiving local anaesthetic infiltration spent on average an estimated 0.83 (95% CI 1.54, 0.12; p = 0.022) and 0.87 (95% CI 1.62, 0.11; p = 0.025) fewer days in hospital after THR and TKR respectively, had reduced opioid consumption, earlier mobilisation, and lower incidence of vomiting.Few studies reported long-term outcomes.Local anaesthetic infiltration is effective in reducing short-term pain and hospital stay in patients receiving THR and TKR. Studies should assess whether local anaesthetic infiltration can prevent long-term pain. Enhanced pain control with additional analgesia through a catheter should be weighed against a possible infection risk.

Project description:BackgroundGenicular artery embolization (GAE) is an innovative technique that has been investigated as a supplementary treatment method for chronic pain secondary to knee osteoarthritis (OA).PurposeTo evaluate the current evidence on the effectiveness and safety of GAE for OA-related knee pain.Study designSystematic review; Level of evidence, 4.MethodsA systematic literature search was conducted in the PubMed, Web of Science, EMBASE, and Scopus databases to identify studies related to knee OA treated with GAE. Treatment agents were categorized as Embozene, imipenem/cilastatin, resorbable microspheres, and polyvinyl alcohol. The main outcomes were the mean difference (MD) in pre- and postembolization pain based on the visual analog scale (VAS) or the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores as well as changes in the need for pain medication. Random- and fixed-effects models were applied for data analysis.ResultsOf 379 initially inspected publications, 11 (N = 225 patients; 268 knees) were included in the final review. The quality of the studies was fair in 8 and poor in 3-categorized according to the National Institutes of Health quality assessment tool. Overall, 119, 72, 13, and 21 patients were treated with imipenem/cilastatin, Embozene, resorbable microspheres, and polyvinyl alcohol, respectively. Symptomatic improvement was reported in all studies. The pooled effect size, characterized by MD, showed a significant improvement in the VAS and WOMAC pain scores, with better functional status after GAE. Pre- versus postembolization MDs in VAS scores ranged from 32 within the first week to 58 after a 2-year follow-up (equivalent to 54% and 80% improvement, respectively). There was a similar trend in the overall WOMAC scores, with MDs ranging from 28.4 to 36.8 (about 58% and 85% improvement, respectively). GAE resulted in a decreased need for pain medication for knee OA, with a 27%, 65%, and 73% decline in the number of patients who used opioids, nonsteroidal anti-inflammatory drugs, and intra-articular hyaluronic acid injection, respectively (P < .00001 for all). No significant difference between embolic agents was seen with regard to post-GAE pain reduction. No severe or life-threatening complications were reported.ConclusionOA treated by GAE using different embolic particles can be considered generally safe, with good efficacy and no reported serious complications.

Dataset Information

Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis.

Publications

Association of Pharmacological Treatments With Long-term Pain Control in Patients With Knee Osteoarthritis: A Systematic Review and Meta-analysis.

Similar Datasets

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