Rheumatoid Arthritis: Moore RA

Clarke R, Derry S, Moore RA, McQuay HJ. · Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU. · Cochrane Database Syst Rev. · Pubmed #19370600 No free full text.

Abstract: BACKGROUND: Etoricoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis, and acute pain. The drug is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). A number of studies in acute postoperative pain have now been published. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single oral dose of etoricoxib for moderate to severe postoperative pain. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Database, and reference lists of articles. Date of the most recent search: December 2008. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled clinical trials of single dose, oral etoricoxib for acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion in the review and quality, and extracted data. The area under the pain relief versus time curve was used to derive the proportion of participants prescribed etoricoxib or placebo with at least 50% pain relief over six hours, using validated equations. Relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Information on use of rescue medication was used to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. Information on adverse effects was also collected. MAIN RESULTS: Five studies (880 participants) were included in the review. All five studies reported on 120 mg, with 655 participants in a comparison with placebo. At least 50% pain relief was reported by 64% with etoricoxib 120 mg and 10% with placebo (NNT 1.9 (1.7 to 2.1)). For dental studies only the NNT was 1.6 (1.5 to 1.8). Two studies also reported on higher doses of 180 and 240 mg, with 249 participants. At least 50% pain relief was reported by 79% with etoricoxib 120 mg and 12% with placebo (NNT 1.5 (1.3 to 1.7)).Significantly fewer participants used rescue medication when taking etoricoxib 120 mg than those taking placebo (NNT to prevent remedication 2.4 (2.1 to 2.9)), and the median time to use of rescue medication was 20 hours. Adverse events were reported at a similar rate to placebo, with no serious events. AUTHORS' CONCLUSIONS: Single dose oral etoricoxib produces high levels of good quality pain relief after surgery. The 120 mg dose is as effective as, or better than, other commonly used analgesics.

Derry S, Barden J, McQuay HJ, Moore RA. · Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU. · Cochrane Database Syst Rev. · Pubmed #18843655 No free full text.

Abstract: BACKGROUND: This is an update of a review published in The Cochrane Library, Issue 1, 2003. Celecoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis. Celecoxib is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). Its effectiveness in acute pain was demonstrated in the earlier review. Additional studies have now been published for the 400 mg dose, and this updated review provides more robust estimates of efficacy and harm. OBJECTIVES: To assess analgesic efficacy and adverse effects of a single oral dose of celecoxib for moderate to severe postoperative pain. SEARCH STRATEGY: Cochrane CENTRAL, MEDLINE, EMBASE, and the Oxford Pain Database. Most recent search: July 2008. SELECTION CRITERIA: Randomised controlled trials (RCTs) of adults prescribed any dose of oral celecoxib or placebo for acute postoperative pain were included. DATA COLLECTION AND ANALYSIS: Eight studies (1380 participants) met the inclusion criteria. Studies were assessed for quality and data extracted by two review authors. Summed pain relief (TOTPAR) or pain intensity difference (SPID) was converted into dichotomous information yielding the number of participants with at least 50% pain relief over four to six hours, and used to calculate the relative benefit (RB) and number-needed-to-treat-to-benefit (NNT) for one patient to achieve at least 50% pain relief with celecoxib who would not have done so with placebo. Information on use of rescue medication was used to calculate the proportion of participants requiring rescue medication and the weighted mean (WM) of the median time to use. MAIN RESULTS: The NNT for celecoxib 200 mg and 400 mg compared with placebo for at least 50% pain relief over four to six hours was 4.2 (CI 3.4 to 5.6) and 2.5 (2.2 to 2.9) respectively. The WM of the median time to use of rescue medication was 6.6 hours with celecoxib 200 mg, 8.4 with celecoxib 400 mg, and 2.3 hours with placebo. The WM proportion of participants requiring rescue medication over 24 hours was 74% with celecoxib 200 mg, 63% for celecoxib 400 mg, and 91% for placebo. The NNT to prevent one patient using rescue medication was 4.8 (3.5 to 7.7) and 3.5 (2.9 to 4.6) for celecoxib 200 mg and 400 mg respectively. One serious adverse event probably related to celecoxib was reported by the trialists. AUTHORS' CONCLUSIONS: Single dose oral celecoxib is an effective means of postoperative pain relief. The 400 mg dose has similar efficacy to ibuprofen 400 mg.

Moore RA, Derry S, Makinson GT, McQuay HJ. · Pain Research and Nuffield Department of Anaesthetics, University of Oxford, Oxford Radcliffe NHS Trust, Oxford, UK. · Arthritis Res Ther. · Pubmed #15899051 links to  free full text

Abstract: The objective was to improve understanding of adverse events occurring with celecoxib in the treatment of osteoarthritis and rheumatoid arthritis. Data were extracted from company clinical trial reports of randomised trials of celecoxib in osteoarthritis or rheumatoid arthritis lasting 2 weeks or more. Outcomes were discontinuations (all cause, lack of efficacy, adverse event, gastrointestinal adverse event), endoscopically detected ulcers, gastrointestinal or cardio-renal events, and major changes in haematological parameters. The main comparisons were celecoxib (all doses) versus placebo, paracetamol (acetaminophen) 4,000 mg daily, rofecoxib 25 mg daily, or nonsteroidal anti-inflammatory drugs (NSAIDs) (naproxen, diclofenac, ibuprofen, and loxoprofen). For NSAIDs, celecoxib was compared both at all doses and at licensed doses (200 to 400 mg daily). Thirty-one trials included 39,605 randomised patients. Most patients had osteoarthritis and were women of average age 60 years or above. Most trials lasted 12 weeks or more. Doses of celecoxib were 50 to 800 mg/day. Compared with placebo, celecoxib had fewer discontinuations for any cause or for lack of efficacy, fewer serious adverse events, and less nausea. It had more patients with dyspepsia, diarrhoea, oedema, more adverse events that were gastrointestinal or treatment related, and more patients experiencing an adverse event. There were no differences for hypertension, gastrointestinal tolerability, or discontinuations for adverse events. Compared with paracetamol, celecoxib had fewer discontinuations for any cause, for lack of efficacy, or diarrhoea, but no other differences. Compared with rofecoxib, celecoxib had fewer patients with abdominal pain and oedema, but no other differences. Compared with NSAIDs, celecoxib had fewer symptomatic ulcers and bleeds, endoscopically detected ulcers, and discontinuations for adverse events or gastrointestinal adverse events. Fewer patients had any, or a gastrointestinal, or a treatment-related adverse event, or vomiting, abdominal pain, dyspepsia, or reduced haemoglobin or haematocrit. Discontinuations for lack of efficacy were higher. No differences were found for all-cause discontinuations, serious adverse events, hypertension, diarrhoea, nausea, oedema, myocardial infarction, cardiac failure, or raised creatinine. Company clinical trial reports present much more information than published papers. Adverse event information is clearly presented in company clinical trial reports, which are an ideal source of information for systematic review and meta-analysis.

Edwards JE, McQuay HJ, Moore RA. · Nuffield Department of Anaesthetics, University of Oxford, Oxford Radcliffe Hospital, The Churchill, Headington, Oxford OX3 7LJ, UK. · Pain. · Pubmed #15363872 No free full text.

Abstract: Our objective was to determine the efficacy and safety of valdecoxib (a cyclo-oxygenase 2 inhibitor) in the treatment of arthritis. Randomised, controlled trials comparing 10 or 20mg valdecoxib with placebo or non-steroidal anti-inflammatory drugs (NSAIDs) in patients with active osteoarthritis or rheumatoid arthritis. The manufacturer provided clinical trial reports. Data were combined through meta-analysis. Main outcomes were patient global rating of arthritis, arthritis pain, Western Ontario and McMaster Universities indices for osteoarthritis, American College of Rheumatology indices for rheumatoid arthritis, discontinuation, endoscopic ulcers, clinically significant upper gastrointestinal or renal events. Nine trials (five in osteoarthritis, four in rheumatoid arthritis) were included with 5726 patients. Overall, valdecoxib 10 and 20mg were superior to placebo and equivalent in efficacy to maximum daily doses of NSAIDs. Significantly fewer discontinuations because of gastrointestinal adverse events (4% versus 8%), or endoscopic ulcers of 3mm or more (5% versus 13%) occurred with valdecoxib compared with NSAIDs. Clinically significant upper gastrointestinal events occurred in 2/2733 (0.1%) with valdecoxib compared with 8/1846 (0.4%) with NSAIDs. Rates of clinically significant renal events were the same (2-3%) for valdecoxib and NSAIDs. At an appropriate dose valdecoxib was as effective as NSAIDs in osteoarthritis and rheumatoid arthritis. There were fewer gastrointestinal adverse event withdrawals and endoscopically detected ulcers. Convincing evidence of reduced major gastrointestinal adverse events could not be addressed by the trials.

Barden J, Edwards JE, McQuay HJ, Moore RA. · Pain Research Unit, University of Oxford, Churchill Hospital, Old Road, Oxford, UK, OX3 7LJ. · Cochrane Database Syst Rev. · Pubmed #12804506 No free full text.

Abstract: BACKGROUND: Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis. The drug is believed to be associated with fewer adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). However, the effectiveness of celecoxib in the treatment of acute pain has not yet been assessed by systematic review. OBJECTIVES: To assess the analgesic efficacy and adverse effects of a single oral dose of celecoxib for moderate to severe postoperative pain. SEARCH STRATEGY: We searched the Cochrane Library Controlled Trials Register, MEDLINE, Biological Abstracts, PubMed and the Oxford Pain database. Date of the most recent search: May 2002. SELECTION CRITERIA: Randomised controlled trials (RCTs) of adults prescribed any dose of oral celecoxib or placebo for acute postoperative pain were included. DATA COLLECTION AND ANALYSIS: Two trials (418 subjects) met the inclusion criteria for this review. The trials were assessed for quality and the data extracted by two independent reviewers. Summed pain relief (TOTPAR) or pain intensity difference (SPID) was extracted and converted into dichotomous information yielding the number of patients with at least 50% pain relief over 4-6 hours. These derived results were used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief. MAIN RESULTS: The number-needed-to-treat for celecoxib 200 mg compared with placebo was 4.5 (CI 3.3 to 7.2). For every 4.5 patients experiencing moderate to severe acute pain treated with celecoxib 200 mg one more will experience at least 50% pain relief that would not have done had they received placebo. The median time to remedication over 24 hours was 5.1 hours with celecoxib 200 mg and 1.5 hours with placebo. Quantitative analysis of adverse effects was not possible but no serious or unexpected adverse effects were reported. REVIEWER'S CONCLUSIONS: Single dose oral celecoxib is an effective means of postoperative pain relief, similar in efficacy to aspirin 600/650 mg, and paracetamol 1000 mg. The two trials included used celecoxib 200 mg, a dose 50% less than is recommended for acute pain. More trials are needed to estimate efficacy for recommended dose of 400 mg, and to reinforce current findings for 200 mg, and provide data for pooled quantitative estimates of adverse effects.

Tirunagari SK, Derry S, Moore RA, McQuay HJ. · Anaesthesia and Critical Care, Oxford Deanery, 10, Norhaw Close, Hemel Hempstead, UK, HP2 7NH. · Cochrane Database Syst Rev. · Pubmed #19588426 No free full text.

Abstract: BACKGROUND: Etodolac is a selective cyclo-oxygenase-2 (COX-2) inhibitor, with evidence of efficacy in osteoarthritis and rheumatoid arthritis. Its analgesic efficacy in postoperative pain has not been clearly established. There are no systematic reviews on Etodolac's use in this condition. OBJECTIVES: To assess the analgesic efficacy of etodolac in single oral doses for moderate and severe postoperative pain. SEARCH STRATEGY: We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to May 2009. SELECTION CRITERIA: Randomised, double blind, placebo-controlled trials of single dose orally administered etodolac (any formulation) in adults with moderate to severe acute postoperative pain. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. MAIN RESULTS: Nine studies (1459 participants) compared etodolac and placebo. Studies were of adequate reporting quality, and the majority of participants had pain following dental extractions. The dose of etodolac used was 25 mg to 1200 mg, with most of the information for 100 mg and 200 mg. For at least 50% pain relief over 4 to 6 hours compared with placebo the NNT for etodolac 100 mg (498 participants) was 4.8 (3.5 to 7.8) and for etodolac 200 mg (670 participants) it was 3.3 (2.7 to 4.2). Very limited information with the extended release formulation did not suggest improved benefit for this outcome.The proportion of participants with at least 50% pain relief was 41% with 100 mg and 44% with 200 mg. Remedication was needed by about 60% with etodolac 200 mg or 400 mg over 6 to 8 hours, compared with almost 80% with placebo.Adverse events were uncommon, and not significantly different form placebo. AUTHORS' CONCLUSIONS: Etodolac 200 mg may be a useful analgesic in postoperative pain, with efficacy similar to paracetamol 1000 mg and celecoxib 200 mg. Higher doses may provide analgesia equivalent to more commonly used drugs, such as ibuprofen 400 mg, naproxen 500 mg and diclofenac 50 mg.

Moore RA, Derry S, McQuay HJ. · Pain Research and Nuffield Department of Anaesthetics, University of Oxford, Oxford Radcliffe Hospital, The Churchill, Oxford OX3 7LJ, UK. · Arthritis Res Ther. · Pubmed #18466615 links to  free full text

Abstract: INTRODUCTION: Patient adherence to therapy in clinical practice is often low, and the difference between efficacy measured in clinical trials and effectiveness in clinical practice is probably a function of discontinuation of therapy because of lack of efficacy or because of unmanageable or intolerable adverse events. Discontinuation is frequently measured in clinical trials but is not usually described in detail in published reports, often because of limitations in the size of publications. By contrast, company clinical trial reports include much more detail. METHODS: We examined company clinical trial reports of trials involving etoricoxib in four musculoskeletal conditions: osteoarthritis, rheumatoid arthritis, chronic low back pain and ankylosing spondylitis. Information was available from 18 randomized trials (10,143 patients) lasting 4 to 12 weeks (one 4 weeks, three 6 weeks, one 8 weeks and seven 12 weeks) and from three trials with a mean duration of about 80 weeks (34,695 patients). These clinical trial reports contain over 73,000 pages of information. RESULTS: Over 12 weeks, lack of efficacy and adverse event discontinuations were similar between osteoarthritis, rheumatoid arthritis and back pain, with lack of efficacy discontinuation rates some three times higher than for adverse events. All-cause and lack of efficacy discontinuations were lower with etoricoxib (all doses combined) and traditional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) than with placebo, although NSAIDs produced higher rates of clinical adverse events and gastrointestinal discontinuations than did placebo. Etoricoxib had fewer discontinuations than NSAIDs for lack of efficacy, clinical adverse events, and laboratory and gastrointestinal adverse events, but with more discontinuations because of hypertension and oedema. Comparison with two similar meta-analyses of other cyclo-oxygenase-2 selective inhibitors (more than 80,000 patients in total) revealed consistency between analyses. CONCLUSION: Examining discontinuation data from clinical trials, even when the numbers of patients are very large, does not necessarily predict what will happen in the real world, where clinical effectiveness may differ from clinical efficacy assessed in trials. Data from these analyses appears to agree with findings from real world practice.