{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:05:47Z","timestamp":1789139147267,"version":"build-2803163510"},"reference-count":16,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":["clinicalkey.jp","scandinavianjournalpain.com","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","clinicalkey.fr","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_j.sjpain.2017.03.006_s_001\">\n                    <jats:title>Background and aim<\/jats:title>\n                    <jats:p>Diclofenac is widely prescribed for the treatment of pain. Several network meta-analyses (NMA), largely of published trials have evaluated the efficacy, tolerability, and safety of nonsteroidal anti-inflammatory drugs (NSAIDs). The present NMA extends these analyses to unpublished older (legacy) diclofenac trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2017.03.006_s_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified randomised controlled trials (RCTs) of diclofenac with planned study duration of at least 4 weeks for the treatment of osteoarthritis (OA) from \u2018legacy\u2019 studies conducted by Novartis but not published in a peer reviewed journal or included in any previous pooled analyses. All studies reporting efficacy and\/or safety of treatment with diclofenac or other active therapies or placebo were included. We used a Bayesian NMA model, and estimated relative treatment effects between pairwise treatments. Main outcomes included pain relief measured using visual analogue scale at 2, 4 and 12 weeks and patient global assessment (PGA) at 4 and 12 weeks for efficacy, all-cause withdrawals, and adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2017.03.006_s_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 19 RCTs (5030 patients) were included; 18 of which were double-blind and one singleblind. All studies were conducted before cyclooxygenase 2 inhibitors (COXIBs) became commercially available. Data permitted robust efficacy comparison between diclofenac and ibuprofen, but the amount of data for other comparators was limited. Diclofenac 150 mg\/day was more efficacious than ibuprofen 1200 mg\/day and had likely favourable outcomes for pain relief compared to ibuprofen 2400 mg\/day. Diclofenac 100 mg\/day had likely favourable outcomes compared to ibuprofen 1200 mg\/day in alleviating pain. Based on PGA, diclofenac 150 mg\/day was more efficacious and likely to be favourable than ibuprofen 1200 mg\/day and 2400 mg\/day, respectively. Risk of withdrawal due to all causes with diclofenac and ibuprofen were comparable. Diclofenac 150 mg\/day was likely to have favourable efficacy and comparable tolerability with diclofenac 100 mg\/day. Results comparing diclofenac and ibuprofen were similar to those from NMAs of published trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2017.03.006_s_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Results from these unpublished \u2018legacy\u2019 studies were similar to those from NMAs of published trials. The favourable efficacy results of diclofenac compared to ibuprofen expand the amount of available evidence comparing these two NSAIDs. The overall benefit-risk profile of diclofenac was comparable to that of ibuprofen in OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_j.sjpain.2017.03.006_s_005\">\n                    <jats:title>Implications<\/jats:title>\n                    <jats:p>The present NMA results reassures that the older unpublished blinded trials have similar results compared to more recently published trials and also contributes to increase the transparency of clinical trials performed with diclofenac further back in the past.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.sjpain.2017.03.006","type":"journal-article","created":{"date-parts":[[2017,4,22]],"date-time":"2017-04-22T20:00:27Z","timestamp":1492891227000},"page":"74-88","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":11,"title":["Efficacy and safety of diclofenac in osteoarthritis: Results of a network meta-analysis of unpublished legacy studies"],"prefix":"10.1515","volume":"16","author":[{"given":"Patricia","family":"Guyot","sequence":"first","affiliation":[{"name":"Health Economics & Outcomes Research, MAPI , Lyon , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaloo","family":"Pandhi","sequence":"additional","affiliation":[{"name":"Global Development, Novartis Pharma AG , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Nixon","sequence":"additional","affiliation":[{"name":"Statistical Methods and Consulting, Novartis Pharma AG , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Drug Safety and Epidemiology, Novartis Healthcare Pvt.Ltd. , Hyderabad , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo L.","family":"Chaves","sequence":"additional","affiliation":[{"name":"Global Medical Affairs, Novartis Pharma AG , Basel , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Andrew","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Pain Research, Nuffield Division of Anaesthetics , University of Oxford , The Churchill , Oxford , United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2017,7,1]]},"reference":[{"key":"2026091114053827072_j_j.sjpain.2017.03.006_ref_001","doi-asserted-by":"crossref","unstructured":"Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, AlMazroa MA, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Bas\u00e1\u00f1ez M-G, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernab\u00e9 E, Bhalla K, Bhandari B, Bikbov B, Abdulhak AB, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braith-waite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng AT-A, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, De Leo D, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett S, Des Jarlais DC, Dharmaratne SD, Dherani M, Diaz-Torne C, Dolk H, Dorsey ER, Driscoll T, Duber H, Ebel B, Edmond K, Elbaz A, Ali SE, Erskine H, Erwin PJ, Espindola P, Ewoigbokhan SE, Farzadfar F, Feigin V, Felson DT, Ferrari A, Ferri CP, F\u00e8vre EM, Finucane MM, Flaxman S, Flood L, Foreman K, Forouzanfar MH, Fowkes FGR, Franklin R, Fransen M, Freeman MK, Gabbe BJ, Gabriel SE, Gakidou E, Ganatra HA, Garcia B, Gaspari F, Gillum RF, Gmel G, Gosselin R, Grainger R, Groeger J, Guillemin F, Gunnell D, Gupta R, Haagsma J, Hagan H, Halasa YA, Hall W, Haring D, Haro JM, Harrison JE, Havmoeller R, Hay RJ, Higashi H, Hill C, Hoen B, Hoffman H, Hotez PJ, Hoy D, Huang JJ, Ibeanusi SE, Jacobsen KH, James SL, Jarvis D, Jasrasaria R, Jayaraman S, Johns N, Jonas JB, Karthikeyan G, Kassebaum N, Kawakami N, Keren A, Khoo J-P, King CH, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lalloo R, Laslett LL, Lathlean T, Leasher JL, Lee YY, Leigh J, Lim SS, Limb E, Lin JK, Lipnick M, Lipshultz SE, Liu W, Loane M, Ohno SL, Lyons R, Ma J, Mabweijano J, MacIntyre MF, Malekzadeh R, Mallinger L, Manivannan S, Marcenes W, March L, Margolis DJ, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGill N, McGrath J, Medina-Mora ME, Meltzer M, Memish ZA, Mensah GA, Merriman TR, Meyer A-C, Miglioli V, Miller M, Miller TR, Mitchell PB, Mocumbi AO, Moffitt TE, Mokdad AA, Monasta L, Montico M, Moradi-Lakeh M, Moran A, Morawska L, Mori R, Murdoch ME, Mwaniki MK, Naidoo K, Nair MN, Naldi L, Narayan KMV, Nelson PK, Nelson RG, Nevitt MC, Newton CR, Nolte S, Norman P, Norman R, O\u2019Donnell M, O\u2019Hanlon S, Olives C, Omer SB, Ortblad K, Osborne R, Ozgediz D, Page A, Pahari B, Pandian JD, Rivero AP, Patten SB, Pearce N, Padilla RP, Perez-Ruiz F, Perico N, Pesudovs K, Phillips D, Phillips MR, Pierce K, Pion S, Polanczyk GV, Polinder S, Pope Iii CA, Popova S, Porrini E, Pourmalek F, Prince M, Pullan RL, Ramaiah KD, Ranganathan D, Razavi H, Regan M, Rehm JT, Rein DB, Remuzzi G, Richardson K, Rivara FP, Roberts T, Robinson C, De Le\u00f2n FR, Ronfani L, Room R, Rosenfeld LC, Rushton L, Sacco RL, Saha S, Sampson U, Sanchez-Riera L, Sanman E, Schwebel DC, Scott JG, Segui-Gomez M, Shahraz S, Shepard DS, Shin H, Shivakoti R, Silberberg D, Singh D, Singh GM, Singh JA, Singleton J, Sleet DA, Sliwa K, Smith E, Smith JL, Stapelberg NJC, Steer A, Steiner T, Stolk WA, Stovner LJ, Sudfeld C, Syed S, Tamburlini G, Tavakkoli M, Taylor HR, Taylor JA, Taylor WJ, Thomas B, Thomson WM, Thurston GD, Tleyjeh IM, Tonelli M, Towbin JA, Truelsen T, Tsilimbaris MK, Ubeda C, Undurraga EA, van der Werf MJ, van Os J, Vavilala MS, Venketasubramanian N, Wang M, Wang W, Watt K, Weatherall DJ, Weinstock MA, Weintraub R, Weisskopf MG, Weissman MM, White RA, Whiteford H, Wiersma ST, Wilkinson JD, Williams HC, Williams SRM, Witt E, Wolfe F, Woolf AD, Wulf S, Yeh P-H, Zaidi AKM, Zheng Z-J, Zonies D, Lopez AD, Murray CJL. 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