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Canadian Journal of Psychiatry. Revue... Jul 2023Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Obsessive-compulsive disorder (OCD) is a major mental health condition with a lifetime prevalence rate of 1.3% among adults. While placebo effects are well described for conditions such as depressive and anxiety disorders, they have not been systematically characterized in OCD.
OBJECTIVES
We aimed to determine the impact of placebos in improving different symptom domains in patients with OCD.
METHODS
We systematically searched PubMed, EMBASE, Scopus, Web of Science, Ovid, the Cochrane Library, and Google Scholar databases/search engine from inception to January 2021 for randomized controlled trials of treatments for OCD with a placebo arm. A modified Cohen's effect size (ES) was calculated using change in baseline to endpoint scores for different measurement scales within placebo arms to estimate placebo effects and to investigate their correlates by random-effects model meta-analyses.
RESULTS
Forty-nine clinical trials (placebo group = 1993), reporting 80 OCD specific (153 measures in general) were included in the analysis. Overall placebo ES (95% confidence interval [CI]) was 0.32 (0.22-0.41) on OCD symptoms, with substantial heterogeneity (I-square = 96.1%). Among secondary outcomes, general scales, ES: 0.27 (95%CI: 0.14-0.41), demonstrated higher ES than anxiety and depression scales, ES: 0.14 (95%CI: -0.4 to 0.32) and 0.05 (95%CI: -0.05 to 0.14), respectively. Clinician-rated scales, ES: 0.27(95%CI: 0.20-0.34), had a higher ES than self-reported scales, ES: 0.07 (95%CI: -0.08 to 0.22). More recent publication year, larger placebo group sample size, shorter follow-up duration, and younger age of participants were all associated with larger placebo ES. Egger's test reflected possible small-study effect publication bias ( = 0.029).
CONCLUSION
Placebo effects are modest in OCD trials and are larger in clinician ratings, for younger patients, and early in the treatment course. These findings underscore the need for clinicians and scientists to be mindful of placebo effects when formulating treatments or research trials for OCD.
SYSTEMATIC REVIEW REGISTRATION NUMBER
PROSPERO CRD42019125979.
Topics: Adult; Humans; Placebo Effect; Obsessive-Compulsive Disorder; Anxiety Disorders
PubMed: 35876317
DOI: 10.1177/07067437221115029 -
Dermatology and Therapy Feb 2023This review's goals were to investigate apremilast's efficacy versus placebo in palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP), and apremilast's efficacy... (Review)
Review
BACKGROUND
This review's goals were to investigate apremilast's efficacy versus placebo in palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP), and apremilast's efficacy versus methotrexate in PP.
METHODS
A literature search was conducted in PubMed, clinicaltrials.gov, and Embase in July 2022. Publications investigating subjects with PP or PPP, treated with apremilast, which reported palmoplantar-specific outcomes were used. Exclusion criteria included cases of drug-induced PP/PPP, case studies, non-English texts, omission of palmoplantar-specific outcomes, and incomplete publications. Studies were assessed for risk of bias using Cochrane Review Manager application and CASP checklist. Primary endpoints were a 50% improvement of the Palmoplantar Psoriasis/Pustulosis Area and Severity Index (PPPASI 50) and improvement of the Palmoplantar Physician Global Assessment (PPPGA) to 0 or 1 in patients with baseline PPPGA ≥ 3.
RESULTS
Seventeen original studies including five placebo-controlled randomized clinical trials (RCTs), one phase II clinical trial, two randomized methotrexate comparative trials, six cohort studies, and three case series were analyzed, totaling 1117 participants. Meta-analysis of four placebo-controlled RCTs investigating PP found apremilast treatment to be superior to placebo in achieving a PPPGA of 0/1 (baseline PPPGA of ≥ 3) after 16 weeks of treatment (n = 244; OR = 2.69 [1.39-5.22]). Apremilast was superior to placebo in achieving PPPASI 50 at week 16 in the only placebo-controlled RCT of PPP (78.3 vs. 40.9%) [P = 0.0003]. Apremilast was comparable to methotrexate in achieving PPPASI 50 at week 16 in PP (59.5 vs. 64.3%; n = 84; [P = 0.65]). Non-randomized studies generally showed marked improvement in PPPASI, PPPGA, and DLQI scores following apremilast treatment.
DISCUSSION
Apremilast treatment in PP and PPP resulted in significant improvement in objective, palmoplantar-specific clinical parameters versus placebo, and comparable efficacy with methotrexate in PP. Limitations in interpreting these results include variations in palmoplantar-specific metrics used and risk of bias of included studies.
PubMed: 36609960
DOI: 10.1007/s13555-022-00877-w -
The Cochrane Database of Systematic... May 2020Aspirin and heparin are widely used as preventive strategy to reduce the high risk of recurrent pregnancy loss in women with antiphospholipid antibodies (aPL). This... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aspirin and heparin are widely used as preventive strategy to reduce the high risk of recurrent pregnancy loss in women with antiphospholipid antibodies (aPL). This review supersedes a previous, out-of-date review that evaluated all potential therapies for preventing recurrent pregnancy loss in women with aPL. The current review focusses on a narrower scope because current clinical practice is restricted to using aspirin or heparins, or both for women with aPL in an attempt to reduce pregnancy complications.
OBJECTIVES
To assess the effects of aspirin or heparin, or both for improving pregnancy outcomes in women with persistent (on two separate occasions) aPL, either lupus anticoagulant (LAC), anticardiolipin (aCL) or aβ-glycoprotein-I antibodies (aβGPI) or a combination, and recurrent pregnancy loss (two or more, which do not have to be consecutive).
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (3 June 2019), and reference lists of retrieved studies. Where necessary, we attempted to contact trial authors.
SELECTION CRITERIA
Randomised, cluster-randomised and quasi-randomised controlled trials that assess the effects of aspirin, heparin (either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH]), or a combination of aspirin and heparin compared with no treatment, placebo or another, on pregnancy outcomes in women with persistent aPL and recurrent pregnancy loss were eligible. All treatment regimens were considered.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion criteria and risk of bias. Two review authors independently extracted data and checked them for accuracy and the certainty of the evidence was assessed using the GRADE approach.
MAIN RESULTS
Eleven studies (1672 women) met the inclusion criteria; nine randomised controlled trials and two quasi-RCTs. The studies were conducted in the USA, Canada, UK, China, New Zealand, Iraq and Egypt. One included trial involved 1015 women, all other included trials had considerably lower numbers of participants (i.e. 141 women or fewer). Some studies had high risk of selection and attrition bias, and many did not include sufficient information to judge the risk of reporting bias. Overall, the certainty of evidence is low to very low due to the small numbers of women in the studies and to the risk of bias. The dose and type of heparin and aspirin varied among studies. One study compared aspirin alone with placebo; no studies compared heparin alone with placebo and there were no trials that had a no treatment comparator arm during pregnancy; five studies explored the efficacy of heparin (either UFH or LMWH) combined with aspirin compared with aspirin alone; one trial compared LMWH with aspirin; two trials compared the combination of LMWH plus aspirin with the combination of UFH plus aspirin; two studies evaluated the combination of different doses of heparin combined with aspirin. All trials used aspirin at a low dose. Aspirin versus placebo We are very uncertain if aspirin has any effect on live birth compared to placebo (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.71 to 1.25, 1 trial, 40 women, very low-certainty evidence). We are very uncertain if aspirin has any effect on the risk of pre-eclampsia, pregnancy loss, preterm delivery of a live infant, intrauterine growth restriction or adverse events in the child, compared to placebo. We are very uncertain if aspirin has any effect on adverse events (bleeding) in the mother compared with placebo (RR 1.29, 95% CI 0.60 to 2.77, 1 study, 40 women). The certainty of evidence for these outcomes is very low because of imprecision, due to the low numbers of women involved and the wide 95% CIs, and also because of risk of bias. Venous thromboembolism and arterial thromboembolism were not reported in the included studies. Heparin plus aspirin versus aspirin alone Heparin plus aspirin may increase the number of live births (RR 1.27, 95% CI 1.09 to 1.49, 5 studies, 1295 women, low-certainty evidence). We are uncertain if heparin plus aspirin has any effect on the risk of pre-eclampsia, preterm delivery of a live infant, or intrauterine growth restriction, compared with aspirin alone because of risk of bias and imprecision due to the low numbers of women involved and the wide 95% CIs. We are very uncertain if heparin plus aspirin has any effect on adverse events (bleeding) in the mother compared with aspirin alone (RR 1.65, 95% CI 0.19 to 14.03, 1 study, 31 women). No women in either the heparin plus aspirin group or the aspirin alone group had heparin-induced thrombocytopenia, allergic reactions, or venous or arterial thromboembolism. Similarly, no infants had congenital malformations. Heparin plus aspirin may reduce the risk of pregnancy loss (RR 0.48, 95% CI 0.32 to 0.71, 5 studies, 1295 women, low-certainty evidence). When comparing LMWH plus aspirin versus aspirin alone the pooled RR for live birth was 1.20 (95% CI 1.04 to 1.38, 3 trials, 1155 women). In the comparison of UFH plus aspirin versus aspirin alone, the RR for live birth was 1.74 (95% CI 1.28 to 2.35, 2 trials, 140 women).
AUTHORS' CONCLUSIONS
The combination of heparin (UFH or LMWH) plus aspirin during the course of pregnancy may increase live birth rate in women with persistent aPL when compared with aspirin treatment alone. The observed beneficial effect of heparin was driven by one large study in which LMWH plus aspirin was compared with aspirin alone. Adverse events were frequently not, or not uniformly, reported in the included studies. More research is needed in this area in order to further evaluate potential risks and benefits of this treatment strategy, especially among women with aPL and recurrent pregnancy loss, to gain consensus on the ideal prevention for recurrent pregnancy loss, based on a risk profile.
Topics: Abortion, Habitual; Antibodies, Anticardiolipin; Antibodies, Antiphospholipid; Anticoagulants; Aspirin; Bias; Drug Therapy, Combination; Female; Heparin; Heparin, Low-Molecular-Weight; Humans; Live Birth; Lupus Coagulation Inhibitor; Placebos; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Randomized Controlled Trials as Topic; beta 2-Glycoprotein I
PubMed: 32358837
DOI: 10.1002/14651858.CD012852.pub2 -
PloS One 2023To assess the benefits and harms of cannabinoids in participants with pain. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To assess the benefits and harms of cannabinoids in participants with pain.
DESIGN
Systematic review of randomised clinical trials with meta-analysis, Trial Sequential Analysis, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
DATA SOURCES
The Cochrane Library, MEDLINE, Embase, Science Citation Index, and BIOSIS.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Published and unpublished randomised clinical trials comparing cannabinoids versus placebo in participants with any type of pain.
MAIN OUTCOME MEASURES
All-cause mortality, pain, adverse events, quality of life, cannabinoid dependence, psychosis, and quality of sleep.
RESULTS
We included 65 randomised placebo-controlled clinical trials enrolling 7017 participants. Fifty-nine of the trials and all outcome results were at high risk of bias. Meta-analysis and Trial Sequential Analysis showed no evidence of a difference between cannabinoids versus placebo on all-cause mortality (RR 1.20; 98% CI 0.85 to 1.67; P = 0.22). Meta-analyses and Trial Sequential Analysis showed that cannabinoids neither reduced acute pain (mean difference numerical rating scale (NRS) 0.52; 98% CI -0.40 to 1.43; P = 0.19) or cancer pain (mean difference NRS -0.13; 98% CI -0.33 to 0.06; P = 0.1) nor improved quality of life (mean difference -1.38; 98% CI -11.81 to 9.04; P = 0.33). Meta-analyses and Trial Sequential Analysis showed that cannabinoids reduced chronic pain (mean difference NRS -0.43; 98% CI -0.72 to -0.15; P = 0.0004) and improved quality of sleep (mean difference -0.42; 95% CI -0.65 to -0.20; P = 0.0003). However, both effect sizes were below our predefined minimal important differences. Meta-analysis and Trial Sequential Analysis indicated that cannabinoids increased the risk of non-serious adverse events (RR 1.20; 95% CI 1.15 to 1.25; P < 0.001) but not serious adverse events (RR 1.18; 98% CI 0.95 to 1.45; P = 0.07). None of the included trials reported on cannabinoid dependence or psychosis.
CONCLUSIONS
Cannabinoids reduced chronic pain and improved quality of sleep, but the effect sizes are of questionable importance. Cannabinoids had no effects on acute pain or cancer pain and increased the risks of non-serious adverse events. The harmful effects of cannabinoids for pain seem to outweigh the potential benefits.
Topics: Humans; Acute Pain; Cancer Pain; Chronic Pain; Quality of Life; Cannabinoids; Analgesics; Sleep; Sleep Quality; Placebos
PubMed: 36716312
DOI: 10.1371/journal.pone.0267420 -
The Cochrane Database of Systematic... Jul 2023Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vedolizumab blocks inflammatory activity within the gastrointestinal tract. Systematic reviews have demonstrated the efficacy of vedolizumab in ulcerative colitis and inflammatory bowel disease in general. This systematic review and meta-analysis summarises the current evidence of vedolizumab in the induction and maintenance of remission in Crohn's disease.
OBJECTIVES
To evaluate the benefits and harms of vedolizumab versus placebo for the induction and maintenance of remission in people with Crohn's disease.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 30 November 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs comparing vedolizumab to placebo for the induction or maintenance of remission in people with Crohn's disease.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. For induction studies, the primary outcome was 1. clinical remission, and secondary outcomes were rates of 2. clinical response, 3. adverse events, 4. serious adverse events, 5. surgery, 6. endoscopic remission and 7. endoscopic response. For maintenance studies, the primary outcome was 1. maintenance of clinical remission, and secondary outcomes were rates of 2. adverse events, 3. serious adverse events, 4. surgery, 5. endoscopic remission and 6. endoscopic response. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We analysed induction (4 trials, 1126 participants) and maintenance (3 trials, 894 participants) studies representing people across North America, Europe, Asia and Australasia separately. One maintenance trial administered subcutaneous vedolizumab whilst the other studies used the intravenous form. The mean age ranged between 32.6 and 38.6 years. Vedolizumab was superior to placebo for the induction of clinical remission (71 more per 1000 with clinical remission with vedolizumab; risk ratio (RR) 1.61, 95% confidence interval (CI) 1.20 to 2.17; number needed to treat for an additional beneficial outcome (NNTB) 13; 4 studies; high-certainty evidence) and superior to placebo for inducing clinical response (105 more per 1000 with clinical response with vedolizumab; RR 1.43, 95% CI 1.19 to 1.71; NNTB 8; 4 studies; high-certainty evidence). For the induction phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (9 fewer serious adverse events per 1000 with vedolizumab; RR 0.91, 95% CI 0.62 to 1.33; 4 studies; low-certainty evidence) and probably equivalent to placebo for overall adverse events (6 fewer adverse events per 1000 with vedolizumab; RR 1.01, 95% CI 0.93 to 1.11; 4 studies; moderate-certainty evidence). Vedolizumab was superior to placebo for the maintenance of clinical remission (141 more per 1000 with maintenance of clinical remission with vedolizumab; RR 1.52, 95% CI 1.24 to 1.87; NNTB 7; 3 studies; high-certainty evidence). During the maintenance phase, vedolizumab may be equivalent to placebo for the development of serious adverse events (3 fewer serious adverse events per 1000 with vedolizumab; RR 0.98, 95% CI 0.68 to 1.39; 3 studies; low-certainty evidence) and probably equivalent to placebo for the development of overall adverse events (0 difference in adverse events per 1000; RR 1.00, 95% CI 0.94 to 1.07; 3 studies; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
High-certainty data across four induction and three maintenance trials demonstrate that vedolizumab is superior to placebo in the induction and maintenance of remission in Crohn's disease. Overall adverse events are probably similar and serious adverse events may be similar between vedolizumab and placebo during both induction and maintenance phases of treatment. Head-to-head research comparing the efficacy and safety of vedolizumab to other biological therapies is required.
Topics: Humans; Adult; Crohn Disease; Antibodies, Monoclonal, Humanized; Colitis, Ulcerative; Inflammatory Bowel Diseases; Remission Induction
PubMed: 37458279
DOI: 10.1002/14651858.CD013611.pub2 -
Journal of Psychiatric Research Jun 2021We examined the efficacy and safety of using antipsychotic medication for schizophrenia using only randomized trials of antipsychotic for schizophrenia conducted in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We examined the efficacy and safety of using antipsychotic medication for schizophrenia using only randomized trials of antipsychotic for schizophrenia conducted in Japan to avoid the biological and environmental heterogeneities caused by pooling data from various races and ethnicities.
METHODS
We searched for eligible studies on Embase, PubMed, and CENTRAL. Primary outcomes were improvement in Positive and Negative Syndrome Scale total score (PANSS-T) and all-cause discontinuation. Other outcomes were improvement in PANSS subscale scores, discontinuation due to adverse events or inefficacy, and the incidence of 16 adverse events.
RESULTS
We calculated mean difference or risk ratios and 95% credible intervals. We identified 34 RCTs (6798 patients; mean study duration, 9.0 ± 4.24 weeks; proportion of male patients, 53.7%; mean age, 43.3 years). Besides placebo, studies included aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, clocapramine (no PANSS data), clozapine (no PANSS data), haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, perospirone, quetiapine, and risperidone. Efficacy and safety profiles differed for antipsychotics used with schizophrenia in Japanese patients. All active treatments other than haloperidol and quetiapine outperformed placebo to improve PANSS-T. Asenapine, olanzapine, paliperidone, and risperidone outperformed placebo for all-cause discontinuation. Asenapine, blonanserin, blonanserin-patch, haloperidol, lurasidone, mosapramine, olanzapine, paliperidone, and risperidone outperformed placebo to improve PANSS positive subscale scores. Aripiprazole, asenapine, blonanserin, blonanserin-patch, brexpiprazole, lurasidone, olanzapine, paliperidone, perospirone, and risperidone outperformed placebo to improve PANSS negative subscale scores. The confidence in evidence of most outcomes was low or very low.
CONCLUSION
Our results are similar to those of previous network meta-analysis involving various races and ethnicities.
Topics: Adult; Antipsychotic Agents; Humans; Japan; Male; Network Meta-Analysis; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 33964682
DOI: 10.1016/j.jpsychires.2021.04.032 -
Rheumatology (Oxford, England) Apr 2022To determine the placebo response rate in PsA randomized clinical trials (RCTs), its contributing factors and impact on the effect size of active treatments. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the placebo response rate in PsA randomized clinical trials (RCTs), its contributing factors and impact on the effect size of active treatments.
METHODS
We searched multiple databases, from inception to 20 December 2020, for placebo-controlled RCTs in PsA. We used a random-effects meta-analysis to pool the response rates for the ACR20 criteria in the placebo arm, determined the risk difference for treatment vs placebo, and used meta-regression to determine the factors associated with placebo response rates. The risk of bias was assessed in duplicate. The study protocol was registered with PROSPERO: CRD42021226000.
RESULTS
We included 42 RCTs (5050 patients receiving placebo) published between 2000 and 2020. The risk of bias was low in 28 trials, high in four, and with some concerns in 10. The pooled placebo response rate was 20.3% (95% CI: 18.6%, 22.1%; predicted intervals, 11.7-29.0%), with significant between-trial heterogeneity (I2 = 56.8%, P < 0.005). The pooled risk difference for treatment vs placebo was 27% (95% CI: 24%, 31%). In the multivariable meta-regression, there was a 15% (95% CI: 2.9%, 29.8%) increase in the odds of achieving the placebo response for each 5-year increment in publication year (P = 0.016). In addition, the active treatment risk difference decreased for every 5-year increment in publication year (β = -0.053, 95% CI: -0.099, -0.007; P = 0.024) but was not associated with the placebo response.
CONCLUSION
Despite increasing over time, the placebo response for ACR20 in PsA RCTs was not associated with the active treatment effect size.
Topics: Arthritis, Psoriatic; Humans; Placebo Effect
PubMed: 34664615
DOI: 10.1093/rheumatology/keab774 -
The Cochrane Database of Systematic... May 2022Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to... (Review)
Review
BACKGROUND
Giant cell arteritis (GCA) is the most common form of systemic vasculitis in people older than 50 years of age. It causes granulomatous inflammation of medium- to large-sized vessels. Tocilizumab is a recombinant monoclonal antibody directed against interleukin-6 receptors (IL-6R).
OBJECTIVES
To assess the effectiveness and safety of tocilizumab, given alone or with corticosteroids, compared with therapy without tocilizumab for treatment of GCA.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2020, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Science Information database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). There were no date or language restrictions in the electronic search for trials. We last searched the electronic databases on 3 January 2020.
SELECTION CRITERIA
We included only randomized controlled trials (RCTs) that compared tocilizumab of any dosage regimen (alone or with corticosteroids) with therapy without tocilizumab that had a minimum follow-up of six months. Participants were at least 50 years of age, with biopsy-proven GCA or by large-vessel vasculitis by angiography, and met the American College of Rheumatology 1990 guidelines for GCA.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology.
MAIN RESULTS
Main results We included two RCTs in the review. The studies were conducted in the USA, Canada, and Europe and enrolled a total of 281 participants with GCA, of whom 74% were women. The mean age of participants was 70 years, with new-onset or relapsing GCA, and fulfilled the 1990 American College of Rheumatology criteria with no uncontrolled comorbidities. Both studies were funded by F. Hoffmann-La Roche AG, the manufacturer of tocilizumab. Findings One RCT (30 participants) compared tocilizumab administered every four weeks versus placebo. Point estimates at 12 months and beyond favored tocilizumab over placebo in terms of sustained remission (risk ratio (RR) 4.25, 95% confidence interval (CI) 1.21 to 14.88; moderate-certainty evidence). Point estimates suggest no evidence of a difference for all-cause mortality at 12 months or more (RR 0.17, 95% CI 0.01 to 3.94; moderate-certainty evidence). At 12 months, mean time to first relapse after induction of remission was 25 weeks in favor of participants receiving tocilizumab compared to placebo (mean difference (MD) 25, 95% CI 11.4 to 38.6; moderate-certainty evidence). The second RCT (250 participants) randomized participants into two intervention and two comparator groups to receive tocilizumab weekly (100 participants), bi-weekly (49 participants), weekly placebo + 26-week taper (50 participants), or weekly placebo + 52-week taper (51 participants). At 12 months, point estimates from this study on proportion of participants with sustained remission favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 3.17, 95% CI 1.71 to 5.89; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 4.00, 95% CI 1.97 to 8.12; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 3.01, 95% CI 1.57 to 5.75; 100 participants); tocilizumab every other week versus placebo + 26-week taper (RR 3.79, 95% CI 1.82 to 7.91; 99 participants) (moderate-certainty evidence). Point estimates on proportion of participants who did not need escape therapy (defined by the study as the inability to keep to the protocol-defined prednisone taper) favored participants who received tocilizumab weekly versus placebo + 52-week taper (RR 1.71, 95% CI 1.24 to 2.35; 151 participants); tocilizumab weekly versus placebo + 26-week taper (RR 2.96, 95% CI 1.83 to 4.78; 150 participants); tocilizumab every other week versus placebo + 52-week taper (RR 1.49, 95% CI 1.04 to 2.14; 100 participants) but not tocilizumab every other week versus placebo + 26-week taper (RR 0.65, 95% CI 0.27 to 1.54; 99 participants) (moderate-certainty evidence). This study did not report mean time to first relapse after induction of remission or all-cause mortality. Across comparison groups, the same study found no evidence of a difference in vision changes and inconsistent evidence with regard to quality of life. Evidence on quality of life as assessed by the physical (MD 8.17, 95% CI 4.44 to 11.90) and mental (MD 5.61, 95% CI 0.06 to 11.16) component score of the 36-Item Short Form Health Survey (SF-36) favored weekly tocilizumab versus placebo + 52-week taper but not bi-weekly tocillizumab versus placebo + 26-week taper (moderate-certainty evidence). Adverse events One RCT reported a lower percentage of participants who experienced serious adverse events when receiving tocilizumab every four weeks versus placebo. The second RCT reported no evidence of a difference among groups with regard to adverse events; however, fewer participants reported serious adverse events in the tocilizumab weekly and tocilizumab biweekly interventions compared with the placebo + 26-week taper and placebo + 52-week taper comparators. Investigators in both studies reported that infection was the most frequently reported adverse event.
AUTHORS' CONCLUSIONS
This review indicates that tocilizumab therapy may be beneficial in terms of proportion of participants with sustained remission, relapse-free survival, and the need for escape therapy. While the evidence was of moderate certainty, only two studies were included in the review, suggesting that further research is required to corroborate these findings. Future trials should address issues related to the required duration of therapy, patient-reported outcomes such as quality of life and economic outcomes, as well as the clinical outcomes evaluated in this review.
Topics: Adrenal Cortex Hormones; Aged; Antibodies, Monoclonal, Humanized; Female; Giant Cell Arteritis; Humans; Male; Recurrence
PubMed: 35560150
DOI: 10.1002/14651858.CD013484.pub3 -
European Journal of Pain (London,... Oct 2021The current treatments of primary musculoskeletal low back pain (LBP) have a low to moderate efficacy, which might be improved by looking at the contribution of placebo... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
The current treatments of primary musculoskeletal low back pain (LBP) have a low to moderate efficacy, which might be improved by looking at the contribution of placebo effects. However, the size of true placebo effects in LBP is unknown. Therefore, a systematic review and meta-analysis were executed of randomized controlled trials investigating placebo effects in LBP.
DATABASES AND DATA TREATMENT
The study protocol was registered in the international prospective register of systematic reviews Prospero (CRD42019148745). A literature search (in PubMed, Embase, The Cochrane Library, CINAHL and PsycINFO) up to 2021 February 16th yielded 2,423 studies. Two independent reviewers assessed eligibility and risk of bias.
RESULTS
Eighteen studies were eligible for the systematic review and 5 for the meta-analysis. Fourteen of the 18 studies were clinical treatment studies, and 4 were experimental studies specifically assessing placebo effects. The clinical treatment studies provided varying evidence for placebo effects in chronic LBP but insufficient evidence for acute and subacute LBP. Most experimental studies investigating chronic LBP revealed significant placebo effects. The meta-analysis of 5 treatment studies investigating chronic LBP depicted a significant moderate effect size of placebo for pain intensity (SMD = 0.57) and disability (SMD = 0.52).
CONCLUSIONS
This review shows a significant contribution of placebo effects to chronic LBP symptom relief in clinical and experimental conditions. The meta-analysis revealed that placebo effects can influence chronic LBP intensity and disability. However, additional studies are required for more supporting evidence and evidence for placebo effects in acute or subacute LBP.
SIGNIFICANCE
This systematic review and meta-analysis provides evidence of true placebo effects in low back pain (LBP). It shows a significant contribution of placebo effects to chronic LBP symptom relief. The results highlight the importance of patient- and context-related factors in fostering treatment effects in this patient group. New studies could provide insight into the potential value of actively making use of placebo effects in clinical practice.
Topics: Chronic Pain; Humans; Low Back Pain; Placebo Effect
PubMed: 34051018
DOI: 10.1002/ejp.1811 -
Otology & Neurotology : Official... Apr 2024To quantify the placebo effect in randomized clinical trials treating tinnitus with oral or intratympanic placebo treatment. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To quantify the placebo effect in randomized clinical trials treating tinnitus with oral or intratympanic placebo treatment.
DATA SOURCES
CINAHL, PubMed, and Scopus were searched for articles from conception to October 2022. MESH and key terms such as "tinnitus," "placebo," and "medication" were used to find randomized, placebo-controlled trials. The search was limited to articles in English.
METHODS
Randomized controlled trials with adult subjects evaluating tinnitus pretreatment and posttreatment with an oral or intratympanic medication versus a placebo arm were included. Crossover studies, studies involving middle/inner ear operations or devices, and studies that exclusively included nonidiopathic etiologies of tinnitus were excluded. Mean tinnitus symptom survey scores for the Tinnitus Handicap Inventory (THI), Tinnitus Severity Index, Tinnitus Functional Index, Tinnitus Handicap Questionnaire, and Visual Analog Scales for tinnitus Intensity/Loudness (VAS-L), Annoyance (VAS-An), and Awareness (VAS-Aw) were extracted for both placebo and experimental groups.
RESULTS
953 studies were screened with 23 studies being included in the final analysis. Meta-analysis of mean difference (MD) was calculated using RevMan 5.4. MD between pretreatment and posttreatment THI scores of the placebo arms was 5.6 (95% confidence interval, 3.3-8.0; p < 0.001). MD between pretreatment and posttreatment VAS scores of the placebo groups for Loudness, Annoyance, and Awareness were 0.8 (0.0 to 1.6, p = 0.05), 0.2 (-0.2 to 0.5, p = 0.34), and 0.3 (-0.0 to 0.7, p = 0.08), respectively.
CONCLUSIONS
Placebo treatment has shown effectiveness in improving patient-reported evaluations of tinnitus when using some standardized metrics such as THI and VAS-L; however, the improvement is not as substantial as nonplacebo treatment.
Topics: Adult; Humans; Tinnitus; Placebo Effect; Randomized Controlled Trials as Topic; Surveys and Questionnaires
PubMed: 38361332
DOI: 10.1097/MAO.0000000000004139