Dataset Information

Tanezumab for Patients with Osteoarthritis of the Knee: A Meta-Analysis.

ABSTRACT:

Objective

Tanezumab is a new therapeutic intervention for patients with osteoarthritis (OA) of the knee. We performed the present meta-analysis to appraise the efficacy and safety of tanezumab for patients with knee OA.

Methods

We systematically searched randomized controlled trials from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The primary outcomes were mean change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, the WOMAC physical function and patient's global assessment (PGA). Outcomes were reported as the standard mean difference (SMD) or relative risk (RR) with 95% confidence interval (CI). We assessed the pooled data using a random-effects model.

Results

Of the identified studies, four were eligible and were included in this meta-analysis (N = 1839 participants). Compared with the placebo groups, tanezumab yielded a significant reduction in mean change in the WOMAC pain (SMD = 0.51, 95% CI 0.34 to 0.69, P<0.00001), the WOMAC physical function (SMD = 0.56, 95% CI 0.38 to 0.74, P<0.00001) and PGA (SMD = 0.34, 95% CI 0.22 to 0.47, P<0.00001). There was no significant difference in serious adverse events (RR = 1.06, 95% CI 0.59 to 1.92, P = 0.84) between the tanezumab and placebo groups. Tanezumab significantly increased discontinuations due to adverse events (RR = 2.89, 95% CI 1.59 to 5.26, P = 0.0005), abnormal peripheral sensations (RR = 3.14, 95% CI 2.12 to 4.66, P<0.00001), and peripheral neuropathy (RR = 6.05, 95% CI 2.32 to 15.81, P = 0.0002).

Conclusion

Tanezumab can alleviate pain and improve function for patients with OA of the knee. However, considering the limited number of studies, this conclusion should be interpreted cautiously and more clinical randomized controlled trials are needed to verify the efficacy and safety of tanezumab for OA of the knee.

SUBMITTER: Kan SL

PROVIDER: S-EPMC4905652 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Publications

Tanezumab for Patients with Osteoarthritis of the Knee: A Meta-Analysis.

Kan Shun-Li SL Li Yan Y Ning Guang-Zhi GZ Yuan Zhi-Fang ZF Chen Ling-Xiao LX Bi Ming-Chao MC Sun Jing-Cheng JC Feng Shi-Qing SQ

PloS one 20160613 6

<h4>Objective</h4>Tanezumab is a new therapeutic intervention for patients with osteoarthritis (OA) of the knee. We performed the present meta-analysis to appraise the efficacy and safety of tanezumab for patients with knee OA.<h4>Methods</h4>We systematically searched randomized controlled trials from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The primary outcomes were mean change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC ...[more]

PMID: 27294371

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Project description:Background/objective:The objective of this study was to investigate the safety and efficacy of subcutaneous (SC) and intravenous (IV) tanezumab administration in osteoarthritis (OA) patients. Materials and methods:Study 1027 (NCT01089725), a placebo-controlled trial, evaluated the efficacy of SC tanezumab (ie, 2.5, 5, and 10 mg) and the therapeutic equivalence of 10 mg tanezumab given subcutaneously versus intravenously every 8 weeks in the symptomatic treatment of OA. Coprimary endpoints were: change from baseline in Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) Pain and Physical Function indices, and Patient's Global Assessment (PGA) of OA. Study 1043 (NCT00994890) was a long-term, noncontrolled safety study of tanezumab (ie, 2.5, 5, and 10 mg) subcutaneously administered every 8 weeks. Both studies were discontinued prematurely due to a US Food and Drug Administration partial clinical hold. Results:Due to the clinical hold, Study 1027 was underpowered, and no statistical analyses were performed. Mean (standard error [SE]) change from baseline to week 8 in WOMAC Pain in tanezumab groups ranged from -3.59 (0.26) to -3.89 (0.32), versus -2.74 (0.25) with placebo. Mean (SE) change from baseline to week 8 in WOMAC Physical Function ranged from -3.13 (0.25) to -3.51 (0.28) with tanezumab and was -2.26 (0.24) with placebo. PGA mean (SE) change from baseline to week 8 ranged from -0.90 (0.11) to -1.08 (0.12) with tanezumab and was -0.78 (0.10) with placebo. Similar effectiveness was associated with tanezumab in Study 1043. Few patients in either study (1.4%-5.2%) discontinued due to adverse events. Five patients required total joint replacements in Study 1027 (placebo, n=2 [2.8%]; tanezumab 2.5 mg, n=3 [4.1%]) and 34 patients in Study 1043 (tanezumab 2.5 mg, n=11 [4.8%]; tanezumab 5 mg, n=8 [3.6%]; tanezumab 10 mg, n=15 [6.6%]). Conclusion:Preliminary results show similar efficacy and safety for both SC and IV administration of tanezumab based on the direct comparisons reported here and indirect comparisons with published results, confirming pharmacokinetic/pharmacodynamic modeling predictions.

Project description:BackgroundIncreased expression of nerve growth factor in injured or inflamed tissue is associated with increased pain. This proof-of-concept study was designed to investigate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that binds and inhibits nerve growth factor.MethodsWe randomly assigned 450 patients with osteoarthritis of the knee to receive tanezumab (administered at a dose of 10, 25, 50, 100, or 200 μg per kilogram of body weight) or placebo on days 1 and 56. The primary efficacy measures were knee pain while walking and the patient's global assessment of response to therapy. We also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety.ResultsWhen averaged over weeks 1 through 16, the mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P<0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients' global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P≤0.001). The rate of response according to the OMERACT-OARSI criteria ranged from 74 to 93% with tanezumab treatment, as compared with 44% with placebo (P<0.001). The rates of adverse events were 68% and 55% in the tanezumab and placebo groups, respectively. The most common adverse events among tanezumab-treated patients were headache (9% of the patients), upper respiratory tract infection (7%), and paresthesia (7%).ConclusionsIn this proof-of-concept study, treatment with tanezumab was associated with a reduction in joint pain and improvement in function, with mild and moderate adverse events, among patients with moderate-to-severe osteoarthritis of the knee. (Funded by Rinat Neuroscience; ClinicalTrials.gov number, NCT00394563.).

Project description:Background: Osteoarthritis (OA) high disability rate will increase as people getting older, and is the most prevalent form of arthritis in the future. This study identified the clinical effects of optimum doses of tanezumab for patients with OA. Method: Three electronic databases were searched up until January 15, 2021. The mean difference (MD) or odds ratio (OR) was considered an effect measure. The design-by-treatment interaction model was adopted for network meta-analyses. Analyses were conducted using WinBUGS 1.4.3 and R 4.0.5 software. Results: nine publications with 10 studies were included. Compared with placebo in network meta-analysis, except the outcomes of Western Ontario and McMaster Universities Osteoarthritis (WOMAC) stiffness subscale and joints replaced, all dosages of tanezumab in the other effectiveness outcome were superior to placebo, and the difference was statistically significant. However, there was no statistical difference among all different doses of tanezumab. Compared with placebo, except the outcomes of adverse events (AEs) and AEs of abnormal peripheral sensation, all different dosages of tanezumab weren't superior to placebo in the other effectiveness outcome, and the difference was statistically significant. The 10 mg of tanezumab with highest SUCRA had the best effect, but it was associated with a higher safety event. Compared with placebo, except the outcomes of WOMAC stiffness subscale and joints replaced, all dosages of tanezumab in the other effectiveness outcome were superior to placebo, and the difference was statistically significant. Compared with placebo, except for the outcomes of AEs and AEs of abnormal peripheral sensation, all dosages of tanezumab in the other effectiveness outcome were superior to placebo, and the difference was statistically significant. Other direct comparisons showed no statistical difference. Conclusion: This study recommended that clinicians should give priority to the treatment of OA patients with a low dose of 2.5 mg according to the patient's condition and actual situation. If the effect using tanezumab with 2.5 mg is not satisfactory, the increase up to 10 mg should be carefully pondered, because of a more unbalanced risk/benefit ratio.

Project description:PurposeA pooled analysis was conducted to evaluate tanezumab efficacy and safety in patients with osteoarthritis (OA), including subgroup analyses of at-risk patients with diabetes, severe OA symptoms, and those aged ≥65 years.Patients and methodsData from phase III placebo-controlled clinical trials of patients with moderate-to-severe OA of the knee or hip were pooled to evaluate tanezumab efficacy (four trials) and safety (nine trials). Patients received intravenous tanezumab, tanezumab plus an oral NSAID (naproxen, celecoxib, or diclofenac), active comparator (naproxen, celecoxib, diclofenac, or oxycodone), or placebo. Efficacy assessments included change from baseline to week 16 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and physical function scores, Patient's Global Assessment (PGA) of OA, and percentage of patients with ≥30%, ≥50%, ≥70%, and ≥90% improvement in WOMAC pain. Safety assessments included adverse event (AE) documentation and physical and neurologic examinations.ResultsTanezumab significantly improved all efficacy end points in the overall population. Efficacy in at-risk patient subgroups was similar to the overall population. Incidence of AEs was highest in the tanezumab plus NSAID group and lowest in the placebo group. Incidence of AEs in the tanezumab monotherapy and active comparator groups was similar. Overall incidence of AEs was similar across subgroups. AEs of abnormal peripheral sensation were more frequently reported in tanezumab-treated patients compared with placebo or active comparator. Patients receiving active comparator had a slightly higher incidence of AEs suggestive of postganglionic sympathetic dysfunction.ConclusionTanezumab consistently provided significant improvement of pain, physical function, and PGA in individuals with OA, including patients with diabetes, severe OA symptoms, or aged ≥65 years. No increased safety risk was observed in at-risk patient subgroups.Trial registrationNCT00733902, NCT00744471, NCT00830063, NCT00863304, NCT00809354, NCT00864097, NCT00863772, NCT01089725, NCT00985621.

Project description:ObjectiveTo evaluate the effectiveness and safety of viscosupplementation for pain and function in patients with knee osteoarthritis.DesignSystematic review and meta-analysis of randomised trials.Data sourcesSearches were conducted of Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to 11 September 2021. Unpublished trials were identified from the grey literature and trial registries.Eligibility criteria for study selectionRandomised trials comparing viscosupplementation with placebo or no intervention for knee osteoarthritis treatment.Main outcome measuresThe prespecified primary outcome was pain intensity. Secondary outcomes were function and serious adverse events. Pain and function were analysed as standardised mean differences (SMDs). The prespecified minimal clinically important between group difference was -0.37 SMD. Serious adverse events were analysed as relative risks.MethodsTwo reviewers independently extracted relevant data and assessed the risk of bias of trials using the Cochrane risk of bias tool. The predefined main analysis was based only on large, placebo controlled trials with ≥100 participants per group. Summary results were obtained through a random effects meta-analysis model. Cumulative meta-analysis and trial sequential analysis under a random effects model were also performed.Results169 trials provided data on 21 163 randomised participants. Evidence of small study effects and publication biases was observed for pain and function (Egger's tests with P<0.001 and asymmetric funnel plots). Twenty four large, placebo controlled trials (8997 randomised participants) included in the main analysis of pain indicated that viscosupplementation was associated with a small reduction in pain intensity compared with placebo (SMD -0.08, 95% confidence interval -0.15 to -0.02), with the lower bound of the 95% confidence interval excluding the minimal clinically important between group difference. This effect corresponds to a difference in pain scores of -2.0 mm (95% confidence interval -3.8 to -0.5 mm) on a 100 mm visual analogue scale. Trial sequential analysis for pain indicated that since 2009 there has been conclusive evidence of clinical equivalence between viscosupplementation and placebo. Similar conclusions were obtained for function. Based on 15 large, placebo controlled trials on 6462 randomised participants, viscosupplementation was associated with a statistically significant higher risk of serious adverse events than placebo (relative risk 1.49, 95% confidence interval 1.12 to 1.98).ConclusionStrong conclusive evidence indicates that viscosupplementation leads to a small reduction in knee osteoarthritis pain compared with placebo, but the difference is less than the minimal clinically important between group difference. Strong conclusive evidence indicates that viscosupplementation is also associated with an increased risk of serious adverse events compared with placebo. The findings do not support broad use of viscosupplementation for the treatment of knee osteoarthritis.Systematic review registrationPROSPERO CRD42021236894.

Project description:ImportancePatients with osteoarthritis (OA) may remain symptomatic with traditional OA treatments.ObjectiveTo assess 2 subcutaneous tanezumab dosing regimens for OA.Design, setting, and participantsA randomized, double-blind, multicenter trial from January 2016 to May 14, 2018 (last patient visit). Patients enrolled were 18 years or older with hip or knee OA, inadequate response to OA analgesics, and no radiographic evidence of prespecified joint safety conditions.InterventionsPatients received by subcutaneous administration either tanezumab, 2.5 mg, at day 1 and week 8 (n = 231); tanezumab, 2.5 mg at day 1 and 5 mg at week 8 (ie, tanezumab, 2.5/5 mg; n = 233); or placebo at day 1 and week 8 (n = 232).Main outcomes and measuresCo-primary end points were change from baseline to week 16 in Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain (0-10, no to extreme pain), WOMAC Physical Function (0-10, no to extreme difficulty), and patient global assessment of osteoarthritis (PGA-OA) (1-5, very good to very poor) scores.ResultsAmong 698 patients randomized, 696 received 1 or more treatment doses (mean [SD] age, 60.8 [9.6] years; 65.1% women), and 582 (83.6%) completed the trial. From baseline to 16 weeks, mean WOMAC Pain scores decreased from 7.1 to 3.6 in the tanezumab, 2.5 mg, group; 7.3 to 3.6 in the tanezumab, 2.5/5 mg, group; and 7.3 to 4.4 in the placebo group (least squares mean differences [95% CI] vs placebo were -0.60 [-1.07 to -0.13; P = .01] for tanezumab, 2.5 mg, and -0.73 [-1.20 to -0.26; P = .002] for tanezumab, 2.5/5 mg). Mean WOMAC Physical Function scores decreased from 7.2 to 3.7 in the 2.5-mg group, 7.4 to 3.6 in the 2.5/5-mg group, and 7.4 to 4.5 with placebo (differences vs placebo, -0.66 [-1.14 to -0.19; P = .007] for tanezumab, 2.5 mg, and -0.89 [-1.37 to -0.42; P < .001] for tanezumab, 2.5/5 mg). Mean PGA-OA scores decreased from 3.4 to 2.4 in the 2.5-mg group, 3.5 to 2.4 in the 2.5/5-mg group, and 3.5 to 2.7 with placebo (differences vs placebo, -0.22 [-0.39 to -0.05; P = .01] for tanezumab, 2.5 mg, and -0.25 [-0.41 to -0.08; P = .004] for tanezumab, 2.5/5 mg). Rapidly progressive OA occurred only in tanezumab-treated patients (2.5 mg: n = 5, 2.2%; 2.5/5 mg: n = 1, 0.4%). The incidence of total joint replacements was 8 (3.5%), 16 (6.9%), and 4 (1.7%) in the tanezumab, 2.5 mg; tanezumab, 2.5/5 mg; and placebo groups, respectively.Conclusions and relevanceAmong patients with moderate to severe OA of the knee or hip and inadequate response to standard analgesics, tanezumab, compared with placebo, resulted in statistically significant improvements in scores assessing pain and physical function, and in PGA-OA, although the improvements were modest and tanezumab-treated patients had more joint safety events and total joint replacements. Further research is needed to determine the clinical importance of these efficacy and adverse event findings.Trial registrationClinicalTrials.gov Identifier: NCT02697773.

Project description:BackgroundGlobally osteoarthritis of the knee is a leading cause of disability. Hip abductor strength and activation are essential for maintaining postural balance during transfers and are related to joint loading and progression during weight-bearing activities. Strength deficits in the hip abductors might cause a reduction in the lower extremity force generation, thereby causing stress on the medial tibiofemoral joint. The aim of this systematic review is to assess the effectiveness of hip abductor strengthening on knee joint loading, knee pain and functional outcome measures in patients with knee osteoarthritis.MethodsDatabase such as Scopus, PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) database and PEDro were reviewed to recognize the trials published in English from inception to December 2020. Randomized controlled trials that studied the effectiveness of hip abductor strengthening in subjects with knee osteoarthritis and its impact on knee joint loading, knee pain and functional outcome measures were included. RevMan 5.4 was used for meta-analysis and forest plot construction. Quality assessment of the included studies was carried out using the PEDro scale.Results and discussionThe search yielded 260 results of which 29 full-text articles were screened. The review includes 7 randomized controlled trials and 3 studies with good methodological quality were included for meta-analysis. The meta-analysis of the articles favored hip abductor strengthening intervention over the control group. Hip abductor strengthening had significantly reduced the VAS [ SMD = -0.60[-0.88, -0.33] p < 0.0001]at 95% CI and improved the WOMAC scores [SMD - 0.75[-1.05,-0.45] p < 0.0001] at 95% CI. All of the included studies concluded that strengthening the hip abductor muscle had a positive impact on knee pain and functional outcomes.ConclusionThe current study found high-quality evidence to support the use of hip abductor muscle strengthening exercises as a rehabilitative treatment for subjects with knee osteoarthritis.Trial registrationCRD42021256251 .

Project description:BackgroundTanezumab is a nerve growth factor monoclonal antibody that may regulate pain in hip or knee osteoarthritis (OA). This meta-analysis was performed to evaluate the efficacy and safety of low and moderate doses of tanezumab in treating hip or knee OA.MethodsPubMed, EMBASE, the Cochrane Library, and Web of Science were comprehensively searched for clinical trials published before 1 May 2021. Patients were assessed via efficacy and safety outcomes.ResultsTwelve randomized controlled trials including 6022 patients were identified. Both low and moderate doses of tanezumab significantly improved efficacy outcomes. However, only the point estimates (mean difference, MD) of moderate-dose tanezumab significantly exceeded the minimal clinically important differences (MCIDs). There were no significant differences in the incidence of treatment-related adverse events (AEs), withdrawals due to AEs, serious AEs, and total joint replacement between the tanezumab and placebo groups, whereas the incidence of AEs was higher in the tanezumab group (relative risk, RR = 1.10; 95% confidence interval, 95% CI = 1.04-1.17). The incidence of rapidly progressive OA was significantly higher in the combined low- and moderate-dose tanezumab groups than in the placebo group (RR = 5.01; 95% CI = 1.17-21.33). Furthermore, both low and moderate doses of tanezumab significantly increased the incidence of abnormal peripheral sensation (RR = 1.99, 95% CI = 1.21-3.28; RR = 2.64, 95% CI = 1.91-3.67, respectively). Compared with nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, tanezumab showed significantly improved efficacy outcomes (p < 0.05). However, the point estimates (MD) of tanezumab were not greater than the MCID. Pooled analysis showed no significant differences between tanezumab and NSAIDs and opioids in safety outcomes (p > 0.05).ConclusionTanezumab is efficacious in patients with hip or knee OA. Tanezumab is relatively well tolerated and safe but increases the incidence of AEs and reversible abnormal peripheral sensation. Additional studies on the occurrence of rapidly progressive OA are needed. A moderate dose of tanezumab may maximize the benefits for hip or knee OA.

Dataset Information

Tanezumab for Patients with Osteoarthritis of the Knee: A Meta-Analysis.

Objective

Methods

Results

Conclusion

Publications

Tanezumab for Patients with Osteoarthritis of the Knee: A Meta-Analysis.

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