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Sao Paulo Medical Journal = Revista... 2011Lumiracoxib is an anti-inflammatory drug that has been used to treat acute dental pain, mainly in postsurgical settings, in which the greatest levels of pain and... (Meta-Analysis)
Meta-Analysis Review
CONTEXT AND OBJECTIVE
Lumiracoxib is an anti-inflammatory drug that has been used to treat acute dental pain, mainly in postsurgical settings, in which the greatest levels of pain and discomfort are experienced during the first 24 hours. This study aimed to assess the efficacy and safety of lumiracoxib for treating acute postsurgical dental pain.
DESIGN AND SETTING
Systematic review developed at the Brazilian Cochrane Centre, Universidade Federal de São Paulo.
METHODS
An electronic search was conducted in the PubMed, Cochrane Library, Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) and Embase databases. A manual search was also performed. Only randomized controlled trials were included, and these were selected and assessed by two researchers with regard to the risk of bias.
RESULTS
Three clinical trials with 921 participants were included. Lumiracoxib 400 mg produced onset of analgesia in a shorter time than shown by lumiracoxib 100 mg, celecoxib 200 mg and ibuprofen 400 mg. There was no difference between lumiracoxib 400 mg and rofecoxib 50 mg. In two studies, the mean time taken to attain onset of analgesia for the placebo was not estimated because the number of participants who reached onset was too small.
CONCLUSION
There is evidence with a moderate risk of bias that recommends the use of lumiracoxib for acute postoperative dental pain. However, the adverse effects are not completely known. Given that lumiracoxib is currently available in only three countries, further studies are likely to be rare and discouraged.
Topics: Acute Pain; Anti-Inflammatory Agents; Cyclooxygenase 2 Inhibitors; Diclofenac; Humans; Pain, Postoperative; Randomized Controlled Trials as Topic; Risk Assessment; Toothache
PubMed: 22069133
DOI: 10.1590/s1516-31802011000500009 -
Academic Emergency Medicine : Official... Sep 2022This review was designated to evaluate the efficacy of parenteral ketorolac in treating acute migraine headache. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This review was designated to evaluate the efficacy of parenteral ketorolac in treating acute migraine headache.
METHODS
We searched databases Cochrane Central Register of Controlled Trials (CENTRAL), Medline, and Google Scholar up to January 2021 and identified randomized controlled trials comparing ketorolac to any other medications in treating patients presenting with migraine headache.
RESULTS
Thirteen trials were included in our review, comprising 944 participants. We derived seven comparisons: ketorolac versus phenothiazines, metoclopramide, sumatriptan, dexamethasone, sodium valproate, caffeine, and diclofenac. There were no significant differences in the reduction of pain intensity at 1 h under the comparisons between ketorolac and phenothiazines (standard mean difference [SMD] = 0.09, p = 0.74) or metoclopramide (SMD = 0.02, p = 0.95). We also found no difference in the outcome recurrence of headache (ketorolac vs. phenothiazines (risk ratio [RR] =0.98, p = 0.97)], ability to return to work or usual activity (ketorolac vs. metoclopramide [RR = 0.64, p = 0.13]), need for rescue medication (ketorolac vs. phenothiazines [RR = 1.72, p = 0.27], ketorolac vs. metoclopramide [RR 2.20, p = 0.18]), and frequency of adverse effects (ketorolac vs. metoclopramide [RR = 1.07, p = 0.82]). Limited trials suggested that ketorolac offered better pain relief at 1 h compared to sumatriptan and dexamethasone; had lesser frequency of adverse effects than phenothiazines; and was superior to sodium valproate in terms of reduction of pain intensity at 1 h, need for rescue medication, and sustained headache freedom within 24 h.
CONCLUSIONS
Ketorolac may have similar efficacy to phenothiazines and metoclopramide in treating acute migraine headache. Ketorolac may also offer better pain control than sumatriptan, dexamethasone, and sodium valproate. However, given the lack of evidence due to inadequate number of trials available, future studies are warranted.
Topics: Caffeine; Dexamethasone; Diclofenac; Humans; Ketorolac; Metoclopramide; Migraine Disorders; Pain; Phenothiazines; Sumatriptan; Valproic Acid
PubMed: 35138658
DOI: 10.1111/acem.14457 -
The Cochrane Database of Systematic... Dec 2011Nearsightedness (myopia) causes blurry vision when looking at distant objects. Highly nearsighted people are at greater risk of several vision-threatening problems such... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nearsightedness (myopia) causes blurry vision when looking at distant objects. Highly nearsighted people are at greater risk of several vision-threatening problems such as retinal detachments, choroidal atrophy, cataracts and glaucoma. Interventions that have been explored to slow the progression of myopia include bifocal spectacles, cycloplegic drops, intraocular pressure-lowering drugs, muscarinic receptor antagonists and contact lenses. The purpose of this review was to systematically assess the effectiveness of strategies to control progression of myopia in children.
OBJECTIVES
To assess the effects of several types of interventions, including eye drops, undercorrection of nearsightedness, multifocal spectacles and contact lenses, on the progression of nearsightedness in myopic children younger than 18 years. We compared the interventions of interest with each other, to single vision lenses (SVLs) (spectacles), placebo or no treatment.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 10), MEDLINE (January 1950 to October 2011), EMBASE (January 1980 to October 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (http://clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 11 October 2011. We also searched the reference lists and Science Citation Index for additional, potentially relevant studies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which participants were treated with spectacles, contact lenses or pharmaceutical agents for the purpose of controlling progression of myopia. We excluded trials where participants were older than 18 years at baseline or participants had less than -0.25 diopters (D) spherical equivalent myopia.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed the risk of bias for each included study. When possible, we analyzed data with the inverse variance method using a fixed-effect or random-effects model, depending on the number of studies and amount of heterogeneity detected.
MAIN RESULTS
We included 23 studies (4696 total participants) in this review, with 17 of these studies included in quantitative analysis. Since we only included RCTs in the review, the studies were generally at low risk of bias for selection bias. Undercorrection of myopia was found to increase myopia progression slightly in two studies; children who were undercorrected progressed on average 0.15 D (95% confidence interval (CI) -0.29 to 0.00) more than the fully corrected SVLs wearers at one year. Rigid gas permeable contact lenses (RGPCLs) were found to have no evidence of effect on myopic eye growth in two studies (no meta-analysis due to heterogeneity between studies). Progressive addition lenses (PALs), reported in four studies, and bifocal spectacles, reported in four studies, were found to yield a small slowing of myopia progression. For seven studies with quantitative data at one year, children wearing multifocal lenses, either PALs or bifocals, progressed on average 0.16 D (95% CI 0.07 to 0.25) less than children wearing SVLs. The largest positive effects for slowing myopia progression were exhibited by anti-muscarinic medications. At one year, children receiving pirenzepine gel (two studies), cyclopentolate eye drops (one study), or atropine eye drops (two studies) showed significantly less myopic progression compared with children receiving placebo (mean differences (MD) 0.31 (95% CI 0.17 to 0.44), 0.34 (95% CI 0.08 to 0.60), and 0.80 (95% CI 0.70 to 0.90), respectively).
AUTHORS' CONCLUSIONS
The most likely effective treatment to slow myopia progression thus far is anti-muscarinic topical medication. However, side effects of these medications include light sensitivity and near blur. Also, they are not yet commercially available, so their use is limited and not practical. Further information is required for other methods of myopia control, such as the use of corneal reshaping contact lenses or bifocal soft contact lenses (BSCLs) with a distance center are promising, but currently no published randomized clinical trials exist.
Topics: Atropine; Child; Contact Lenses; Cyclopentolate; Disease Progression; Eyeglasses; Humans; Muscarinic Antagonists; Myopia; Ophthalmic Solutions; Pirenzepine; Randomized Controlled Trials as Topic
PubMed: 22161388
DOI: 10.1002/14651858.CD004916.pub3 -
BMJ Open Sep 2020To assess the comparative efficacy of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 inhibitors in patients with acute gout. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the comparative efficacy of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 inhibitors in patients with acute gout.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
Medline, Web of Science, China National Knowledge Infrastructure and Wanfang Data published as of 4 April 2020.
METHODS
We performed meta-analysis of randomised controlled trials (RCTs) of traditional non-selective NSAIDs versus cyclo-oxygenase-2 inhibitors and RCTs of various cyclo-oxygenase-2 inhibitors in patients with acute gout. The main outcome measures were mean change in pain Visual Analogue Scale (VAS) score and 5-point Likert scale score on days 2-8.
RESULTS
Twenty-four trials involving five drugs were evaluated. For pain Likert scale, etoricoxib was comparable to indomethacin (standardised mean difference (SMD): -0.09, 95% CI: -0.27 to 0.08) but better than diclofenac 50 mg three times a day (SMD: -0.53, 95% CI: -0.98 to 0.09). Regarding pain VAS score, etoricoxib was comparable to diclofenac 75 mg two times per day (SMD: -1.63, 95% CI: -4.60 to 1.34) and diclofenac 75 mg four times a day (SMD: -1.82, 95% CI: -5.18 to 1.53), while celecoxib was comparable to diclofenac 100 mg four times a day (SMD: -2.41, 95% CI: -5.91 to 1.09). Etoricoxib showed similar patients' global assessment of response (SMD: -0.10, 95% CI: -0.27 to 0.07) and swollen joint count (SMD: -0.25, 95% CI: -0.74 to 0.24), but better investigator's global assessment of response (SMD: -0.29, 95% CI: -0.46 to 0.11) compared with indomethacin. Etoricoxib showed more favourable pain VAS score than celecoxib (SMD: -2.36, 95% CI: -3.36 to 1.37), but was comparable to meloxicam (SMD: -4.02, 95% CI: -10.28 to 2.24). Etoricoxib showed more favourable pain Likert scale than meloxicam (SMD: -0.56, 95% CI: -1.10 to 0.02). Etoricoxib 120 mg four times a day was more likely to achieve clinical improvement than celecoxib 200 mg two times per day (OR: 4.84, 95% CI: 2.19 to 10.72).
CONCLUSION
Although cyclo-oxygenase-2 inhibitors and traditional non-selective NSAIDs may be equally beneficial in terms of pain relief, cyclo-oxygenase-2 inhibitors (especially etoricoxib) may confer a greater benefit.
Topics: Anti-Inflammatory Agents, Non-Steroidal; China; Diclofenac; Etoricoxib; Gout; Humans
PubMed: 32912981
DOI: 10.1136/bmjopen-2019-036748 -
Drugs & Aging Apr 2019We aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to assess the safety of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.
METHODS
A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with topical NSAIDs in patients with OA were eligible for inclusion. Authors and/or study sponsors were contacted to obtain the full report of AEs. The primary outcomes were overall severe and serious AEs, as well as the following MedDRA System Organ Class (SOC)-related AEs: gastrointestinal, vascular, cardiac, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue.
RESULTS
The search strategy identified 1209 records, from which 25 papers were included in the qualitative synthesis and 19 were included in the meta-analysis, after exclusions. Overall, more total AEs (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.04-1.29; I = 0.0%) and more withdrawals due to AEs (OR 1.49, 95% CI 1.15-1.92; I = 0.0%) were observed with topical NSAIDs compared with placebo. The same results were achieved with topical diclofenac, largely driven by an increase in skin and subcutaneous tissue disorders (OR 1.73, 95% CI 0.96-3.10), although the difference was not statistically significant compared with placebo. No significant difference in the odds for gastrointestinal disorders was observed between topical NSAIDs and placebo (OR 0.96, 95% CI 0.73-1.27).
CONCLUSIONS
Topical NSAIDs may be considered safe in the management of OA, especially with regard to low gastrointestinal toxicity. The use of topical NSAIDs in OA should be considered, taking into account their risk: benefit profile in comparison with other anti-OA treatments.
Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Drug-Related Side Effects and Adverse Reactions; Humans; Osteoarthritis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31073923
DOI: 10.1007/s40266-019-00661-0 -
The Cochrane Database of Systematic... Jul 2010Lumiracoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. COX-2 inhibitors were developed to avoid COX-1-related gastrointestinal (GI) problems while maintaining... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Lumiracoxib is a selective cyclooxygenase-2 (COX-2) inhibitor. COX-2 inhibitors were developed to avoid COX-1-related gastrointestinal (GI) problems while maintaining the analgesic and anti-inflammatory activity of traditional non-steriodal anti-inflammatory drugs (NSAIDs).
OBJECTIVES
To review the analgesic efficacy, duration of analgesia, and adverse effects of a single oral dose of lumiracoxib for moderate to severe postoperative pain in adults.
SEARCH STRATEGY
We searched Cochrane CENTRAL, MEDLINE, and EMBASE to February 2010.
SELECTION CRITERIA
Single oral dose, randomised, double-blind, placebo-controlled trials of lumiracoxib for relief of established moderate to severe postoperative pain in adults.
DATA COLLECTION AND ANALYSIS
Studies were assessed for methodological quality and the data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR 6) was used to calculate the number of participants achieving at least 50% pain relief. These derived results were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Numbers of participants using rescue medication, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected.
MAIN RESULTS
In this updated review four studies met the inclusion criteria. In total 366 participants were treated with lumiracoxib 400 mg, 51 with lumiracoxib 100 mg, and 212 with placebo. Active comparators were naproxen 500 mg, rofecoxib 50 mg, celecoxib 200 mg, celecoxib 400 mg, and ibuprofen 400 mg. With lumiracoxib 400 mg 50% of participants had at least 50% pain relief over six hours, compared with 8% given placebo; RB 6.9 (95% CI 4.1 to 12), NNT 2.4 (2.1 to 2.8).Median time to onset of analgesia was shorter for lumiracoxib 400 mg (0.6 to 1.5 hours) than placebo (>12 hours). Fewer participants needed rescue medication with lumiracoxib (64%) than with placebo (91%) over 12 to 24 hours; NNT to prevent remedication 3.7 (2.9 to 5.0). The weighted median time to use of rescue medication was 9.4 hours for lumiracoxib 400 mg and 1.7 hours for placebo.Adverse events were generally mild to moderate in severity, with one serious event reported in a placebo patient.
AUTHORS' CONCLUSIONS
Lumiracoxib 400 mg given as a single oral dose is an effective analgesic for acute postoperative pain, and has a relatively long duration of action. Adverse events with lumiracoxib did not differ from placebo.
Topics: Acute Disease; Administration, Oral; Adult; Cyclooxygenase 2 Inhibitors; Diclofenac; Humans; Pain, Postoperative; Randomized Controlled Trials as Topic; Time Factors
PubMed: 20614451
DOI: 10.1002/14651858.CD006865.pub2 -
Pancreas Aug 2015To identify the factors affecting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing post-endoscopic retrograde cholangiopancreatography (ERCP)... (Meta-Analysis)
Meta-Analysis Review
Factors Affecting the Efficacy of Nonsteroidal Anti-inflammatory Drugs in Preventing Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Systematic Review and Meta-analysis.
OBJECTIVES
To identify the factors affecting the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP).
METHODS
We systematically searched databases for relevant studies published from inception to November 2013.
RESULTS
A meta-analysis of 11 randomized trials (n = 2497) revealed a significant reduction in PEP in patients who received NSAIDs compared with that in patients who received placebo (relative risk [RR], 0.59; 95% confidence interval [CI], 0.41-0.85; P = 0.005). In subgroup analysis by treatment type, indomethacin had no significant effect (RR, 0.66; 95% CI, 0.38-1.15; P = 0.14), whereas other NSAIDs showed significant benefit (RR, 0.51; 95% CI, 0.29-0.91; P = 0.02). Only rectal administration significantly reduced the incidence of PEP (RR, 0.43; 95% CI, 0.32-0.58; P < 0.00001). The risk for PEP was the lowest among patients who received NSAIDs before ERCP (RR, 0.48; 95% CI, 0.29-0.78; P = 0.003). NSAIDs did not significantly reduce the risk of PEP in men (RR, 0.61; 95% CI, 0.34-1.09), patients with sphincter of Oddi dysfunction (RR, 0.98; 95% CI, 0.38-2.54), or patients with pancreatic duct injection (RR, 0.64; 95% CI, 0.35-1.18).
CONCLUSIONS
Rectal administration of NSAIDs (especially diclofenac), before ERCP, seemed to be the most effective strategy for preventing PEP.
Topics: Administration, Rectal; Anti-Inflammatory Agents, Non-Steroidal; Chi-Square Distribution; Cholangiopancreatography, Endoscopic Retrograde; Diclofenac; Drug Administration Schedule; Humans; Odds Ratio; Pancreatitis; Protective Factors; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 26168316
DOI: 10.1097/MPA.0000000000000326 -
Daru : Journal of Faculty of Pharmacy,... Dec 2019The study systematically reviewed the effectiveness of pharmacological treatments alone or combined with brief cognitive-behavioural therapy (BCBT) for treating Iranian... (Comparative Study)
Comparative Study
OBJECTIVES
The study systematically reviewed the effectiveness of pharmacological treatments alone or combined with brief cognitive-behavioural therapy (BCBT) for treating Iranian amphetamine abusers. The secondary aim was to review the efficacy of BCBT alone or combined with pharmacological treatments for treating amphetamine abusers in the world.
EVIDENCE ACQUISITION
Published trials were considered for inclusion. The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Web of Science, MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, Cochrane Drugs and Alcohol Group's Specialised Register of Trials, Embase, CINAHL, Scopus, PsychINFO, Iran Medex, Magiran and the Scientific Information Database were searched (January 2001 to March 2019). The reference lists of included studies were hand searched for more information. A systematic literature search in eight databases produced 10 trials.
RESULTS
Risperidone reduced positive psychotic symptoms while aripiprazole reduced negative psychotic symptoms. Methylphenidate reduced craving and depression compared with placebo. Topiramate reduced addiction severity and craving for methamphetamine abuse compared with placebo. Buprenorphine reduced methamphetamine craving more than methadone. Haloperidol and risperidone reduced psychosis. Riluzole reduced craving, withdrawal, and depression compared with placebo. Abstinence from amphetamine or reduction in amphetamine abuse was confirmed in four BCBT studies and one study which applied BCBT with a pharmacological treatment which were stable between two and 12-months. Other changes in BCBT studies were as follows: reduced polydrug use; drug injection, criminality and severity of amphetamine dependence at six-month follow-up; improved general functioning; mental health; stage of change as well as improved motivation to change in a pharmacological + BCBT study.
CONCLUSION
A review of trials indicates that pharmacological treatments and BCBT in a research setting outperform control conditions in treating amphetamines abuse and associated harms. Large-scale studies should determine if both treatments can be effective in clinical settings.
Topics: Amphetamine-Related Disorders; Aripiprazole; Clinical Trials as Topic; Cognitive Behavioral Therapy; Combined Modality Therapy; Humans; Iran; Methylphenidate; Risperidone
PubMed: 31228128
DOI: 10.1007/s40199-019-00282-3 -
Current Oncology (Toronto, Ont.) Apr 2018Our objective was to determine whether, compared with control interventions, pharmacologic interventions reduce the severity of fatigue in patients with cancer or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Our objective was to determine whether, compared with control interventions, pharmacologic interventions reduce the severity of fatigue in patients with cancer or recipients of hematopoietic stem-cell transplantation (hsct).
METHODS
For a systematic review, we searched medline, embase, the Cochrane Central Register of Controlled Trials, cinahl, and Psychinfo for randomized trials of systemic pharmacologic interventions for the management of fatigue in patients with cancer or recipients of hsct. Two authors independently identified studies and abstracted data. Methodologic quality was assessed using the Cochrane Risk of Bias tool. The primary outcome was fatigue severity measured using various fatigue scales. Data were synthesized using random-effects models.
RESULTS
In the 117 included trials (19,819 patients), the pharmacologic agents used were erythropoietins ( = 31), stimulants ( = 19), l-carnitine ( = 6), corticosteroids ( = 5), antidepressants ( = 5), appetite stimulants ( = 3), and other agents ( = 48). Fatigue was significantly reduced with erythropoietin [standardized mean difference (smd): -0.52; 95% confidence interval (ci): -0.89 to -0.14] and with methylphenidate (smd: -0.36; 95% ci: -0.56 to -0.15); modafinil (or armodafinil) and corticosteroids were not effective.
CONCLUSIONS
Erythropoietin and methylphenidate significantly reduced fatigue severity in patients with cancer and in recipients of hsct. Concerns about the safety of those agents might limit their usefulness. Future research should identify effective interventions for fatigue that have minimal adverse effects.
Topics: Central Nervous System Stimulants; Erythropoietin; Fatigue; Hematopoietic Stem Cell Transplantation; Humans; Methylphenidate; Neoplasms; Severity of Illness Index
PubMed: 29719440
DOI: 10.3747/co.25.3883 -
The Cochrane Database of Systematic... Oct 2014Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to reduce inflammatory pain and swelling in inflammatory bowel disease (IBD) patients with rheumatological... (Review)
Review
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to reduce inflammatory pain and swelling in inflammatory bowel disease (IBD) patients with rheumatological manifestations. While these drugs effectively reduce musculoskeletal pain and stiffness, long-term use is limited by gastrointestinal (GI) adverse effects (AEs) and disease exacerbation. As an alternative to NSAIDs, selective cyclooxygenase 2 (COX-2) inhibitors were developed to improve GI safety and tolerability. COX-2 inhibitors include drugs such as celecoxib, rofecoxib, valdecoxib, etoricoxib, and lumiracoxib. Rofecoxib and valdecoxib have been withdrawn from the market worldwide due to safety concerns (most importantly for cardiovascular adverse events) and lumiracoxib has been withdrawn in many countries due to liver toxicity. However, celecoxib and etoricoxib continue to be available for use in many countries. Several studies have examined whether COX-2 inhibitors can be safely used for the treatment of rheumatological manifestations of IBD with inconsistent results. Some investigators report acceptable safety profiles associated with these drugs while others found that COX-2 inhibitors are associated with high rates of disease exacerbation.
OBJECTIVES
The objective of this systematic review was to evaluate the tolerability and safety of COX-2 inhibitors used for the treatment of rheumatological manifestations of IBD.
SEARCH METHODS
We searched the following databases from inception to 19 September 2013: PubMed, EMBASE, MEDLINE and CENTRAL. The search was not limited by language. Additional trials were identified by manually searching the reference lists of relevant papers and conference proceedings and through correspondence with experts and pharmaceutical companies.
SELECTION CRITERIA
Randomized controlled trials (RCTs) that compared COX-2 inhibitors to placebo were considered for inclusion. Participants were adult patients with IBD presenting with rheumatological manifestations of at least two weeks duration.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial eligibility and extracted data. Methodological quality was assessed using the Cochrane risk of bias tool. The primary outcome measure was the proportion of patients with disease exacerbation as defined by the included studies. Secondary outcomes included GI adverse effects, renal toxicity, cardiovascular and thrombotic events. Data were analysed on an intention-to-treat basis where patients with missing final outcomes were assumed to have had an exacerbation of IBD. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes. The overall quality of the evidence was assessed using the GRADE criteria.
MAIN RESULTS
There were no RCTs that assessed the tolerability or safety of the withdrawn COX-2 inhibitors rofecoxib, valdecoxib, or lumiracoxib. Two RCTs (n = 381 IBD patients with rheumatological manifestations) were included in the review. One study (n = 159) compared etoricoxib (60 to 120 mg/day) to placebo in IBD patients with quiescent or active ulcerative colitis or Crohn's disease. The other study (n = 222) compared celecoxib (200 mg twice daily) to placebo in patients with quiescent ulcerative colitis. Both studies were judged to be at low risk of bias. The two included studies were not pooled for meta-analysis due to differences in patient populations and treatment duration. There was no statistically significant difference in exacerbation of IBD between etoricoxib and placebo. After 12 weeks of treatment the IBD exacerbation rate was 17% (14/82) in the etoricoxib group compared to 19% (15/77) in the placebo group (RR 0.88, 95% CI 0.45 to 1.69). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (29 events). There was no statistically significant difference in exacerbation of ulcerative colitis between celecoxib and placebo. After two weeks of treatment 4% (5/112) of celecoxib patients experienced an exacerbation of ulcerative colitis compared to 6% (7/110) of patients in the placebo group (RR 0.70, 95% CI 0.23 to 2.14). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (12 events). The study comparing etoricoxib to placebo documented but did not report on AEs. The proportion of patients who experienced AEs was similar in the celecoxib and placebo groups (21% and 17%, respectively, P > 0.20). No patients in either group died or experienced serious adverse events. Eleven percent of patients in the celecoxib and placebo groups experienced GI AEs (RR 0.97, 95% CI 0.46 to 2.07). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to very sparse data (24 events). GI AEs led to premature withdrawal from the study in 3% of patients in celecoxib and placebo groups respectively. GI AEs included increased stool frequency, rectal bleeding, and inflamed mucosa. No patients experienced any cardiovascular adverse events. Renal toxicity or thrombotic AEs were not reported.
AUTHORS' CONCLUSIONS
The results for disease exacerbation and AEs between the COX-2 inhibitors celecoxib and etoricoxib and placebo were uncertain. Thus no definitive conclusions regarding the tolerability and safety of the short term use of celecoxib and etoricoxib in patients with IBD can be drawn. The two included studies suggest that celecoxib and etoricoxib do not exacerbate IBD symptoms. However, it should be noted that both studies had relatively small sample sizes and short follow-up durations. Clinicians need to continue to weigh the risks and benefits of these drugs when treating patients IBD patients with rheumatological manifestations in order to avoid disease exacerbation and other adverse effects. Further RCTs are needed to determine the tolerability and safety of celecoxib and etoricoxib in these patients.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Colitis, Ulcerative; Crohn Disease; Cyclooxygenase 2 Inhibitors; Diclofenac; Etoricoxib; Humans; Isoxazoles; Lactones; Pyrazoles; Pyridines; Randomized Controlled Trials as Topic; Safety-Based Drug Withdrawals; Sulfonamides; Sulfones
PubMed: 25340915
DOI: 10.1002/14651858.CD007744.pub2