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Efficacy of tanezumab vs. placebo on pain, function, safety for patients with knee OA
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December 2016
Efficacy of tanezumab vs. placebo on pain, function, safety for patients with knee OA
Study Type:Therapy
OE Level Evidence:1
Journal Level of Evidence:N/A
Tanezumab for Patients with Osteoarthritis of the Knee: A Meta-Analysis
PLoS One. 2016 Jun 13;11(6):e0157105.Did you know you're eligible to earn 0.5 CME credits for reading this report? Click Here
Synopsis
4 randomized controlled trials (n=1833 patients) were included in this meta-analysis for the purpose of comparing analgesic efficacy and safety of tanezumab when compared to placebo treatment. Outcomes of interest included changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, WOMAC physical function, patient global assessment, the incidence of adverse events, and treatment discontinuation due to adverse effects. Results demonstrated that patients who were given tanezumab had significantly improved pain, function, and global assessment scores when compared to the placebo group. However, significant increases in therapy discontinuation due to adverse effects, development of abnormal peripheral sensation, and peripheral neuropathy were also observed.
Publication Funding Details
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Funding:
Non-Industry funded
Sponsor:
State Key Program of National Natural Science Foundation of China, Special Program for Sino-Russian Joint Research Sponsored by the Ministry of Science and Technology, and Key Program Sponsored by the Tianjin Science and Technology Committee
Conflicts:
None disclosed
Were the search methods used to find evidence (original research) on the primary question or questions stated?
Was the search for evidence reasonably comprehensive?
Were the criteria used for deciding which studies to include in the overview reported?
Was the bias in the selection of studies avoided?
Were the criteria used for assessing the validity of the included studies reported?
Was the validity of all of the studies referred to in the text assessed with use of appropriate criteria (either in selecting the studies for inclusion or in analyzing the studies that were cited)?
Were the methods used to combine the findings of the relevant studies (to reach a conclusion) reported?
Were the findings of the relevant studies combined appropriately relative to the primary question that the overview addresses?
Were the conclusions made by the author or authors supported by the data and or analysis reported in the overview?
How would you rate the scientific quality of this evidence?
Yes = 1
Uncertain = 0.5
Not Relevant = 0
No = 0
The Reporting Criteria Assessment evaluates the transparency with which authors report the methodological and trial characteristics of the trial within the publication. The assessment is divided into five categories which are presented below.
4/4
Introduction
4/4
Accessing Data
3/4
Analysing Data
4/4
Results
2/4
Discussion
Detsky AS, Naylor CD, O'Rourke K, McGeer AJ, L'Abbé KA. J Clin Epidemiol. 1992;45:255-65
The Fragility Index is a tool that aids in the interpretation of significant findings, providing a measure of strength for a result. The Fragility Index represents the number of consecutive events that need to be added to a dichotomous outcome to make the finding no longer significant. A small number represents a weaker finding and a large number represents a stronger finding.
Why was this study needed now?
First-line treatment for pain associated with osteoarthritis of the knee often includes paracetamol, non-steroidal anti-inflammatory drugs, and other select analgesic medication. Although the efficacy of these treatments has been established through research for the majority of patients with knee OA, there still remains the potential risk of hepatotoxicity, gastrointestinal distress, and cardiorenal side effects. Tanezumab, a newly developed monoclonal antibody, has shown a promising effect in selectively inhibiting nerve growth factor (NGF), a critical element in the experience of osteoarthritic pain. A recent study has shown promising therapeutic efficacy when compared to placebo, however, its use in patients with knee OA specifically has been sparse and inconclusive.
What was the principal research question?
What is the efficacy and safety of the use of Tanezumab for pain associated with osteoarthritis of the knee in terms of improvement in pain, function, patient global assessment, and incidence of adverse events?
Study Characteristics
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Data Source:
PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for potential studies for inclusion up to July 25, 2015. References lists of eligible studies were also manually searched for any additional articles of relevance.
Index Terms:
Index terms included “Tanezumab” and “knee osteoarthritis”; terms were additionally combined with Boolean operators for search strategy.
Study Selection:
4 randomized controlled trials investigating the use of Tanezumab for the treatment of knee osteoarthritis were included in this meta-analysis. Eligible articles were required to possess the following four criteria: (1) patients enrolled had a diagnosis of knee OA according to the American College of Rheumatology with at least a grade of 2 on the Kellgren-Lawrence grading scale, (2) patients received intravenous administration of Tanezumab, (3) comparisons were made to placebo therapy, and (4) outcomes included WOMAC pain, WOMAC function, patient global assessment (PGA), adverse events, incidence of abnormal peripheral sensations, and incidence of peripheral neuropathy. Study screening and selection was performed by two independent investigators, with conflicts resolved by a discussion with a third reviewer.
Data Extraction:
Data extraction was performed by two independent investigators, with discrepancies resolved by a third reviewer. Mean change in WOMAC pain, WOMAC physical function, and PGA were defined as the primary outcomes of this analysis; secondary outcomes included discontinuation due to adverse events, the incidence of serious adverse events, abnormal peripheral sensations, and peripheral neuropathy.
Data Synthesis:
All statistical analyses were performed with Review Manager (version 5.3). Dichotomous outcomes were assessed with calculated relative risk (RR) and associated 95% confidence intervals (CI) and a random-effects model was used to estimate pooled outcomes without the influence of heterogeneity. Heterogeneity was calculated with I^2 statistics, where values above 50% were labeled as significantly heterogeneous. The Quality of Evidence and Risk of Bias assessments were completed with GRADE and the Cochrane Handbook for Systematic Reviewers of Interventions respectively.
What were the important findings?
- When compared to placebo, tanezumab groups demonstrated a significantly greater reduction in WOMAC pain scores (4 studies, n=1833 patients; SMD= 0.51 [95% CI 0.34-0.69], p<0.00001, I^2= 48%). (GRADE level of evidence: moderate)
- Tanezumab groups demonstrated a significantly greater reduction in WOMAC physical function scores when compared to placebo (4 studies, n=1833 patients; SMD=0.56 [95% CI 0.38-0.74], p<0.00001, I^2=52%). (GRADE level of evidence: low)
- Tanezumab groups demonstrated significantly greater improvement in PGA scores when compared to placebo (2 studies; SMD= 0.34 [95% CI 0.22-0.47], p<0.00001, I^2=0%). (GRADE level of evidence: moderate)
- When compared to placebo, tanezumab demonstrated a significantly higher risk of therapy discontinuation due to adverse events (3 studies; RR=2.89 [95% CI 1.59-5.26], p=0.0005, I^2=0%). (GRADE level of evidence: very low)
- Differences in incidence of serious adverse events (defined by requiring significant hospital intervention or causing disability, congenital anomaly, or death) were not significant between tanezumab and placebo groups (4 studies; RR=1.06 [95% CI 0.59-1.92], p=0.84, I^2=0%). (GRADE level of evidence: low)
- Tanezumab groups demonstrated a significant increase in the incidence of abnormal peripheral sensations when compared placebo (4 studies; RR=3.14 [95% CI 2.12-4.66], p<0.00001, I^2=16%). (GRADE level of evidence: low)
- Tanezumab groups demonstrated a significant increase in the incidence of peripheral neuropathy when compared the placebo group (2 studies; RR=6.05 [95% CI 2.32-15.81], p=0.0002, I^2=0%). (GRADE level of evidence: low)
- Subgroup analysis revealed that primary outcomes measures were not significantly different between tanezumab and placebo groups when tested for administration frequency (twice or thrice daily) or phase of the trial (phase II vs. phase III).
What should I remember most?
For patients with osteoarthritis of the knee, treatment with tanezumab resulted in significant improvements in WOMAC pain, WOMAC function, and patient global assessment while maintaining comparable incidence of serious adverse events when compared to placebo therapy. However, tanezumab was associated with a significantly increased risk of therapy discontinuation due to adverse events, particularly due abnormal peripheral sensation and peripheral neuropathy.
How will this affect the care of my patients?
The results of this meta-analysis suggest that tanezumab may be of clinical benefit for patients with knee osteoarthritis as evidenced by significant improvements in pain, function, and assessment when compared to placebo. Significantly higher risks of therapy discontinuation (due to adverse effects), development of abnormal peripheral sensation and neuropathy were also noted. Further investigation with controlled methodology is recommended for validation of significant benefits. Direct comparisons made between tanezumab therapy and other popular modes of analgesic relief is also recommended to additionally compare the clinical and safety outcomes.
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