scholarly journals Targeting Nerve Growth Factor, a new option for treatment of osteoarthritis: A Network meta-analysis of comparative efficacy and safety with traditional drugs

2020 ◽  
Author(s):  
Ziqin Cao ◽  
Pengcheng Dou ◽  
Zeling Long ◽  
Yihan Li ◽  
Jingjing Sun ◽  
...  

Abstract BACKGROUND: Osteoarthritis (OA) is the most common joint disease and leading cause of pain and disability in the elderly population. Most guidelines recommend the use non-steroidal anti-inflammatory drugs (NSAIDs) and opioids for the non-operative treatment of OA. Monoclonal NGF antibodies are potential for pain relief and function improvement of OA. We conducted this network meta-analysis to comprehensively compare the efficacy and safety of monoclonal NGF antibodies with NSAIDs and opioids for OA. METHODS: Relevant studies, published up to January 2020, were included from PubMed, CKNI and Web of Science databases. Bayesian network and conventional meta-analyses were conducted. Pain relief, function improvement and risk of adverse effects (AEs) were assessed. RESULTS: 38 articles, comprising 41 trials (20489 patients with OA) were included. Overall, Anti-NGF was the most efficacious drug for pain relief (SMD compared with placebo 4.25, 95% CIs [2.87 to 5.63], SUCRA=93.7%) and (SMD 4.90, 95% CIs [3.46 to 6.33], SUCRA=98.3%). Although Anti-NGF was associated with higher risk of peripheral sensation abnormality (paresthesia and pruritus), it was not associated with higher withdrawal rates due to AEs and ohter AEs. CONCLUSIONS: The results show that monoclonal NGF antibodies significantly relieve pain due to OA and improve function, compared to selective cox-2 inhibitions, NSAIDs, and opioids. The monoclonal NGF antibodies are not associated with severe AEs. However, there is need to conduct more studies to confirm the findings of this study.

2017 ◽  
Vol 16 (1) ◽  
pp. 74-88 ◽  
Author(s):  
Patricia Guyot ◽  
Shaloo Pandhi ◽  
Richard M. Nixon ◽  
Asif Iqbal ◽  
Ricardo L. Chaves ◽  
...  

AbstractBackground and aimDiclofenac is widely prescribed for the treatment of pain. Several network meta-analyses (NMA), largely of published trials have evaluated the efficacy, tolerability, and safety of nonsteroidal anti-inflammatory drugs (NSAIDs). The present NMA extends these analyses to unpublished older (legacy) diclofenac trials.MethodsWe identified randomised controlled trials (RCTs) of diclofenac with planned study duration of at least 4 weeks for the treatment of osteoarthritis (OA) from ‘legacy’ studies conducted by Novartis but not published in a peer reviewed journal or included in any previous pooled analyses. All studies reporting efficacy and/or safety of treatment with diclofenac or other active therapies or placebo were included. We used a Bayesian NMA model, and estimated relative treatment effects between pairwise treatments. Main outcomes included pain relief measured using visual analogue scale at 2, 4 and 12 weeks and patient global assessment (PGA) at 4 and 12 weeks for efficacy, all-cause withdrawals, and adverse events.ResultsA total of 19 RCTs (5030 patients) were included; 18 of which were double-blind and one singleblind. All studies were conducted before cyclooxygenase 2 inhibitors (COXIBs) became commercially available. Data permitted robust efficacy comparison between diclofenac and ibuprofen, but the amount of data for other comparators was limited. Diclofenac 150 mg/day was more efficacious than ibuprofen 1200 mg/day and had likely favourable outcomes for pain relief compared to ibuprofen 2400 mg/day. Diclofenac 100 mg/day had likely favourable outcomes compared to ibuprofen 1200 mg/day in alleviating pain. Based on PGA, diclofenac 150 mg/day was more efficacious and likely to be favourable than ibuprofen 1200 mg/day and 2400 mg/day, respectively. Risk of withdrawal due to all causes with diclofenac and ibuprofen were comparable. Diclofenac 150 mg/day was likely to have favourable efficacy and comparable tolerability with diclofenac 100 mg/day. Results comparing diclofenac and ibuprofen were similar to those from NMAs of published trials.ConclusionsResults from these unpublished ‘legacy’ studies were similar to those from NMAs of published trials. The favourable efficacy results of diclofenac compared to ibuprofen expand the amount of available evidence comparing these two NSAIDs. The overall benefit-risk profile of diclofenac was comparable to that of ibuprofen in OA.ImplicationsThe present NMA results reassures that the older unpublished blinded trials have similar results compared to more recently published trials and also contributes to increase the transparency of clinical trials performed with diclofenac further back in the past.


2020 ◽  
Author(s):  
Ziqin Cao ◽  
Xutao Hu ◽  
Jian Zhou ◽  
Tong Wu ◽  
Dilihumaer Aili ◽  
...  

Abstract OBJECTIVEOsteoarthritis (OA) is the most common form of joint disease which usually affects load-bearing joints such as hip and knee joints. Most guidelines recommend the use non-steroidal anti-inflammatory drugs (NSAIDs), duloxetine and tramadol for the non-operative treatment of OA, the use of them is limited by the tolerability and safety concerns. Lutikizumab is a novel anti–IL-1α/β dual variable domain immunoglobulin that can simultaneously binds and inhibits IL-1α and IL-1β to relieve the pain and dysfunction symptoms. We conducted this network meta-analysis to comprehensively compare the clinical efficacy and safety of lutikizumab with other drugs recommended by guidelines.DESIGNSystematic review and Bayesian network meta-analysis.DATA SOURCESAll eligible studies in PubMed, CKNI, EMBASE and Web of Science databases, from January 2000 to January 2020.METHODSBayesian network and conventional meta-analyses were conducted. Pain relief, function improvement and risk of adverse effects (AEs) were assessed.RESULTS24 articles with 11858 patients were included. Lutikizumab showed no benifit compared with placebo for both pain relief (SMD 1.11, 95% CI [-2.29 to 4.52]) and function improvement (SMD 0.992, 95% CI [-0.433 to 4.25]). Lutikizumab and all other drugs are of favorable tolerance for patients in treatment of OA compared with placebo.CONCLUSIONSThe results show that lutikizumab, the new anti–Interleukin-1α/β dual variable domain immunoglobulin, did not improve pain or function in the comparison with placebo. Selective cox-2 inhibitors remain the most effective and safest treatment for osteoarthritis. More high-quality trials are still needed to reconfirm the findings of this study.


BMJ Open ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. e022142
Author(s):  
Jun Wang ◽  
Yin Wang ◽  
Hui Zhang ◽  
Ming Lu ◽  
Weilu Gao ◽  
...  

IntroductionOsteoarthritis is a common degenerative joint disease that eventually leads to disability and poor quality of life. The main symptoms are joint pain and mobility disorders. If the patient has severe pain or other analgesics are contraindicated, opioids may be a viable treatment option. To evaluate and compare the efficacy and safety of opioids in the treatment of knee or hip osteoarthritis, we will integrate direct and indirect evidence using a Bayesian network meta-analysis to establish hierarchies of these drugs.Methods and analysisWe will search the Medical Literature Analysis and Retrieval System Online, Excerpta Medica database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Web of Science and PsycINFO databases as well as published and unpublished research in international registries and regulatory agency websites for osteoarthritis reports published prior to 5 January 2018. There will be no restrictions on the language. Randomised clinical trials that compare oral or transdermal opioids with other various opioids, placebo or no treatment for patients with knee or hip osteoarthritis will be included. The primary outcomes of efficacy will be pain and function. We will use pain and function scales to evaluate the main outcomes. The secondary outcomes of safety will be defined as the proportion of patients who have stopped treatment due to side effects. Pairwise meta-analyses and Bayesian network meta-analyses will be performed for all related outcome measures. We will conduct subgroup analyses and sensitivity analyses to assess the robustness of our findings. The Grading of Recommendations, Assessment, Development and Evaluations framework will be used to assess the quality of the evidence contributing to each network assessment.Ethics and disseminationThis study does not require formal ethical approval because individual patient data will not be included. The findings will be disseminated through peer-reviewed publications or conference presentations.PROSPERO registration numberCRD42018085503.


2018 ◽  
Vol 47 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Falan Luo ◽  
Xinyu Huang ◽  
Xiaohui Liu ◽  
Lijun Wang ◽  
Nenggui Xu

Background Acupuncture and non-steroidal anti-inflammatory drugs (NSAIDs) are used frequently to treat primary dysmenorrhoea. However, it is unclear whether this treatment greatly reduces the risk of primary dysmenorrhoea. Methods Eight databases were searched up to January 2018. Pair-wise and network meta-analyses were conducted to synthesize data from eligible studies. Results Seventeen randomized controlled trials were included. The following acupuncture types showed more efficacy than NSAIDs in reducing primary dysmenorrhoea risk: traditional acupuncture (odds ratio [OR] = 6.70, 95% confidence interval [CI] 2.60–20.0), eye acupuncture (OR = 3.50, 95% CI 1.40–8.90), wrist–ankle acupuncture (OR = 6.00, 95% CI 1.30–32.0), superficial acupuncture (OR= 5.10, 95% CI 1.20–26.0), moxibustion (OR = 7.70, 95% CI 2.90–25.0), electroacupuncture (OR = 23.0, 95% CI 4.80–130), ear acupuncture (OR = 13.0, 95% CI 2.80–100) and abdominal acupuncture (OR = 5.30, 95% CI 2.10–16.0). Surface under the cumulative ranking curve values were traditional acupuncture (53.0%), eye acupuncture (22.0%), wrist–ankle acupuncture (81.5%), superficial acupuncture (50.0%), moxibustion (57.8%), electroacupuncture (99.9%), ear acupuncture (41.6%) and abdominal acupuncture (44.1%). Conclusion Acupuncture is more efficacious than NSAIDs in reducing primary dysmenorrhoea risk. Acupuncture, particularly electroacupuncture, can decrease the risk of primary dysmenorrhoea.


Author(s):  
Pu Chen ◽  
Liuwei Huang ◽  
Yufeng Ma ◽  
Dong Zhang ◽  
Xiaozhe Zhang ◽  
...  

Abstract Objective The purpose of this study was (1) to perform a summary of meta-analyses comparing platelet-rich plasma (PRP) injection with hyaluronic acid (HA) and placebo injection for KOA patients, (2) to determine which meta-analysis provides the best available evidence to making proposals for the use of PRP in the treatment of KOA patients, and (3) to highlight gaps in the literature that require future investigation. Material and methods PubMed, EMBASE, and Cochrane databases search were performed for meta-analyses which compared PRP injection with HA or placebo. Clinical outcomes and adverse events were extracted from these meta-analyses. Meta-analysis quality was assessed using the Quality of Reporting of Meta-analyses (QUOROM) systems and the Oxman-Guyatt quality appraisal tool. The Jadad decision algorithm was also used to determine which meta-analysis provided the best available evidence. Results Four meta-analyses were included in our study, and all of these articles were Level I evidence. The QUOROM score of each included meta-analysis range from 14 to 17 points (mean score 15, maximum score 18), and the Oxman-Guyatt score range from 4 to 6 points (mean score 5, maximum score 7). Three meta-analyses indicated PRP showed more benefit in pain relief and functional improvement than the control group, and the other one suggested no difference between these groups. All included meta-analyses found no statistical difference in adverse events between these groups. In addition, a meta-analysis conducted by Shen et al. got the highest methodological quality score and suggested that PRP provided better pain relief and function improvement in the treatment of KOA. Conclusions For short-term follow-up (≤1 year), intra-articular PRP injection is more effective in terms of pain relief and function improvement in the treatment of KOA patients than HA and placebo, and there is no difference in the risk of an adverse event between PRP and HA or placebo. Level of evidence Level I evidence, a summary of meta-analyses Trial registration PROSPERO ID CRD42018116168


2021 ◽  
Vol 5 (1) ◽  
pp. e001129
Author(s):  
Bill Stevenson ◽  
Wubshet Tesfaye ◽  
Julia Christenson ◽  
Cynthia Mathew ◽  
Solomon Abrha ◽  
...  

BackgroundHead lice infestation is a major public health problem around the globe. Its treatment is challenging due to product failures resulting from rapidly emerging resistance to existing treatments, incorrect treatment applications and misdiagnosis. Various head lice treatments with different mechanism of action have been developed and explored over the years, with limited report on systematic assessments of their efficacy and safety. This work aims to present a robust evidence summarising the interventions used in head lice.MethodThis is a systematic review and network meta-analysis which will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement for network meta-analyses. Selected databases, including PubMed, Embase, MEDLINE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials will be systematically searched for randomised controlled trials exploring head lice treatments. Searches will be limited to trials published in English from database inception till 2021. Grey literature will be identified through Open Grey, AHRQ, Grey Literature Report, Grey Matters, ClinicalTrials.gov, WHO International Clinical Trials Registry and International Standard Randomised Controlled Trials Number registry. Additional studies will be sought from reference lists of included studies. Study screening, selection, data extraction and assessment of methodological quality will be undertaken by two independent reviewers, with disagreements resolved via a third reviewer. The primary outcome measure is the relative risk of cure at 7 and 14 days postinitial treatment. Secondary outcome measures may include adverse drug events, ovicidal activity, treatment compliance and acceptability, and reinfestation. Information from direct and indirect evidence will be used to generate the effect sizes (relative risk) to compare the efficacy and safety of individual head lice treatments against a common comparator (placebo and/or permethrin). Risk of bias assessment will be undertaken by two independent reviewers using the Cochrane Risk of Bias tool and the certainty of evidence assessed using the Grading of Recommendations, Assessment, Development and Evaluations guideline for network meta-analysis. All quantitative analyses will be conducted using STATA V.16.DiscussionThe evidence generated from this systematic review and meta-analysis is intended for use in evidence-driven treatment of head lice infestations and will be instrumental in informing health professionals, public health practitioners and policy-makers.PROSPERO registration numberCRD42017073375.


2021 ◽  
Author(s):  
Alaa Abd-alrazaq ◽  
Dari Alhuwail ◽  
Eiman Al-Jafar ◽  
Arfan Ahmed ◽  
Shuja Mohd Reagu ◽  
...  

BACKGROUND Memory, one of the main cognitive functions, is known to decline by age. Serious games have been used for improving memory among the elderly. The effectiveness of serious games in improving memory has been investigated by several systematic reviews; however, they are limited by design and methodological weaknesses. OBJECTIVE This study aims to assess the effectiveness of serious games in improving memory among the elderly with cognitive impairment. METHODS A systematic review of randomized controlled trials (RCTs) was carried out. The search sources included searching 8 databases, screening reference lists of the included studies and relevant reviews, and checking studies that cited the included studies. Two reviewers independently carried out the study selection, data extraction, risk of bias assessment, and quality of evidence appraisal. Extracted data were synthesized using a narrative approach and a statistical approach (i.e., meta-analysis), as appropriate. RESULTS Out of 466 citations retrieved, 18 studies met the eligibility criteria of this review. Of those, 15 RCTs were eventually included in 10 meta-analyses. We found that serious games are more effective than no or passive interventions in improving non-verbal memory (P=0.002) and working memory (P=0.02), but not verbal memory (P=0.13). The review also showed that serious games are more effective than conventional exercises in improving verbal memory (P=0.004), but not for non-verbal memory (P=0.12) and working memory (P=0.49). Serious games were as effective as conventional cognitive activities in improving verbal memory (P=0.07), non-verbal memory (P=0.94), and working memory (P=0.08) among the elderly with cognitive impairment. Lastly, the effect of adaptive serious games on working memory was comparable to non-adaptive serious games (P=0.08). CONCLUSIONS Serious games have the potential to improve verbal, non-verbal, and working memory among elderly people with cognitive impairment. However, our findings should be interpreted cautiously given that most meta-analyses were based on a few studies (≤3) and judged to have a low quality of evidence. Therefore, serious games should be offered as supplemental to existing proven and safe interventions, rather than a complete substitute until further, more robust evidence is available. Future studies should investigate the short and long-term effects of serious games on memory and other cognitive abilities among people from different age groups with or without cognitive impairment.


2006 ◽  
Vol 20 (8_suppl) ◽  
pp. 25-30
Author(s):  
Reinhard Sittl

Transdermal buprenorphine has been assessed as a therapy for chronic cancer and non-cancer pain in both clinical and postmarketing surveillance studies. Data from 239 patients who had participated in a follow-up study of up to six years have shown efficacy and safety, and good tolerability over prolonged treatment periods with a marked stability of doses. From the cancer pain population (134 patients), 20% stayed on transdermal buprenorphine until the end of their lives. Postmarketing surveillance study data from 13 179 patients, including 3690 cancer patients assessed during a 10-week observation period, showed that 81% of patients achieved good/very good pain relief with transdermal buprenorphine. Furthermore, 49.6% of patients did not require any analgesic comedication or rescue therapy, a point that is particularly important in the elderly population. Results from the Spanish Pain Society on transdermal buprenorphine in chronic non-cancer, neuropathic and cancer-related pain, and on switching from morphine, also confirmed its beneficial efficacy and safety, and showed that buprenorphine does not antagonize pain relief, or cause withdrawal when combined with full μ-agonists. The effectiveness of buprenorphine is further supported by evidence of its pronounced anti-hyperalgesic effect in a human pain model, which may be a factor in explaining the efficacy of buprenorphine in neuropathic pain. When switching of opioids is indicated to improve pain relief or reduce adverse events, equipotency dosage ratios are important. The equipotency ratio for morphine to buprenorphine, previously established as 75:1, is now being questioned as new data from a retrospective cohort study were published indicating a ratio of 100:1. Moreover, transdermal buprenorphine has superior safety in respect to respiratory depression, immunological and renal effects compared with standard World Health Organization step III opioids, which makes it highly suitable for treating moderate-to-severe pain also in cancer patients, a per se vulnerable patient population requiring a sensible selection of potent analgesics.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Thirumalaivasan Dhasakeerthi ◽  
Muhammad Ishfaq ◽  
Balaji Krishnaiah ◽  
Andrei Alexandrov ◽  
Georgios Tsivgoulis

Background: Post-stroke depression is common and it impedes rehabilitation and function recovery after stroke, and numerous trials evaluated SSRI’s for depression prophylaxis. The objective of this study is to assess the use of SSRI for prevention of poststroke depression and the potential effect on functional recovery after stroke. Methods: We searched electronic databases up to July 2019 for randomized controlled trials of SSRI’s for patients with stroke versus placebo. We calculated pooled odds ratios and 95% CIs by using random-effects models. The primary end points were depression and good functional outcome (modified Rankin Scale score of 0-2) at 90 days post-randomization. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Twelve randomized control trials assessing 4,887 patients have been included in the meta-analysis. SSRI treatment after stroke decreased the odds of depression compared to control group (OR = 0.48, 95% CI - 0.30 to 0.78, p=0.003). There was no heterogeneity between the trials (Cochran’s Q statistic 4.623, df 5; P = .337, I 2 =5.626%). The proportion of subjects who achieved mRS 0-2 at 90 days was similar between SSRI and control groups (OR= 3.471, 95% CI - 0.59 to 20.38, p=0.168). Conclusion: SSRI treatment for the stroke patients reduces the incidence of depression but it does not increase the odds of good functional recovery.


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