Reachout Orthopedics - Issue 1

treatments. Etoricoxib is a new highly selec- tive COX-2 inhibitor [12, 13] that has shown anti-inflammatory, analgesic, and antipyretic activities in models of acute and chronic pain and inflammation, and it has better GI tol- erability compared to NSAIDs [14–16]. We performed a systematic review and meta- analysis to study the efficacy and safety of etoricoxib in the treatment of acute gout, as compared to NSAIDs. Materials and Methods Literature Search We conducted a computerized search of electronic databases: PubMed, EMBASE, Web of Science, China Biology Medicine disc, and Cochrane Library. The search terms were as follows: gout, etoricoxib, indomethacin diclofenac, and NSAIDs. Articles were searched from 1983 until August 2014. A manual search of peer-reviewed English documents was performed by cross-checking the bibliographies of selected studies. If multiple articles of the same patient population were identified, we only included the published report with the largest sample size. We did not search for unpublished investigations. Inclusion and Exclusion Criteria We included articles with patients diagnosed according to the American Rheumatology Association diagnostic criteria for acute gout [17]. Articles were excluded if they were editorials, observational studies, case reports, author replies, review articles, opinions, comments, or any other non-RCTs. Studies not pertinent to gout, hyperuricemia, or tophus were excluded. Studies that included other arthritic diseases that could confound or interfere with efficacy evaluations or those that did not report clinical outcomes were also excluded. Data Analysis Data extraction was performed by SZ and checked by JW using a predefined data extraction form. Discrepancies were resolved by discussion between reviewers. For each study, reviewers extracted data that were deemed to potentially impact efficacy outcomes, such as study population (percent women, mean age, and severity of gout arthritis), study design (duration, concomitant analgesic use, and intervention method), and outcomes (patient’s assessment of pain, tenderness and swelling score at endpoint, and change from baseline with measures of variance; adverse events). Two authors (SZ and YZ) assessed included articles independently and used the “assessing risk of bias” tool recommended in the Cochrane Handbook 5.0.2 to evaluate the risk of bias of included trials. The tool assesses factors including random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. Another two authors (ZW and LP) settled disputes when there was no consensus. For continuous outcomes, we pooled data with the weighted mean difference (WMD) of the final value across groups. For dichotomous data, we calculated the relative risks (RRs) and 95 % confidence interval (CI) for each study. The meta-analysis was performed on data extracted from the studies. If the standard deviations (SDs) were not reported, we calculated the SD with the 95 % CI. Before data analysis, the Q statistic was calculated to assess heterogeneity. We used the fixed effect model when the effects were assumed to be homogenous ( p >0.05) and the random effect model when they were heterogeneous ( p <0.05). All statistical tests and risk of bias were calculated with RevMan 5.2 (Cochrane Collaboration, London, UK). Results Identification and Selection of Studies A total of 165 records (86 from EMBASE, 5 from Cochrane Library, 13 from PubMed MEDLINE, 44 from Web of Science, 16 from China Biology Medicine disc, and 1 identified from other sources) were obtained from the initial search. All studies were selected strictly according to the criteria described. After 41 duplicates, 73 reviews, 11 conference papers, 4 case reports, 4 short surveys, 4 notes, and 3 editorials were removed. Twenty-five studies remained for the full-text review. Nineteen studies were ultimately excluded because they are not related to acute gout or the control group did not take NSAIDs. Finally, six trials were included [9, 18–22]. The selection process and reasons for exclusion are summarized in Fig. 1. Description and Quality of Studies In three articles [9, 18, 19] directly comparing etoricoxib and indomethacin for the treatment of acute gout, all trials reported pain relief (patients’ personal assessments of pain in the study joint on a 0–4-point scale) as the primary outcome. Tenderness, swelling, patients’ global assessments of response to treatment, and investigators’ global assessments of response to treatment were reported as the secondary outcomes. Another three [20–22] were comparing etoricoxib and diclofenac for the treatment of acute gout, two trials [20, 21] assessed pain relief by a visual analogue scale, and another one was [22] assessed by the criteria of Mazur (1979). Both six articles reported adverse events for safety assessment. Six articles were included in this meta-analysis. Studies were evaluated with the “assessing risk of bias” tool, and results are summarized in Fig. 2. All studies aimed to assess the efficacy and safety of etoricoxib for the treatment of acute gout. The control group in each study was indomethacin and diclofenac. All eligible patients were 18 years or older with acute gout associated with moderate, severe, or extreme pain and meeting the American Rheumatology Association diagnostic criteria for acute gout [17]. The three studies included 851 patients. Etoricoxib, indomethacin, and diclofenac were not the only drugs given to patients. Patients could take low-dose aspirin (<325mgdaily), allopurinol if taken for at least two weeks before the trials, and colchicines (<1.2 mg daily) if taken at a stable dose for more than 30 days before the trials. Studies were not included if patients were allowed any other NSAIDs or analgesics within 48 h before baseline assessments, within six hours of baseline assessments, or for the duration of the study. The demographic characteristics of patients are summarized in Table 1. Cyclooxygenase 2 (COX-2) inhibitors are an option for patients with gastrointestinal contraindications or intolerance to NSAIDs. 9 reachOut Orthopedics