title: Dose modifications of anti-TNF drugs in rheumatoid arthritis patients under real-world settings: a systematic review.
abstract: Anti-TNF dose modifications in rheumatoid arthritis have implications on healthcare resource utilization. The objective was to systematically review the dose modifications, both escalations and reductions, of currently available anti-TNF drugs (adalimumab, certolizumab, etanercept, golimumab and infliximab) in the real-world setting. We performed a systematic literature search of MEDLINE, ISI Web of Science, EMBASE, Indice Médico Español databases and American College of Rheumatology and European League Against Rheumatism annual congresses databases. PRISMA and MOOSE guidelines were followed. Only observational studies were included. Clinical trials were excluded since they do not reflect routine clinical practice. Dose escalations and reductions of the anti-TNF drug and their magnitude were collected. Thirty-four studies fulfill the inclusion criteria. Etanercept was associated with the lower percentage of patients under dose escalation (4.5 %; range 0-22 %), both in naïve (4.9 %) and non-naïve patients (1.3 %). Adalimumab and infliximab were associated with significantly higher percentages. Dose modification magnitude in those patients compared to basal dose was significantly different between treatments; 7.1 % (95 % CI 6.3-7.9 %) in etanercept, 30.4 % (95 % CI 28.3-32.5 %) in adalimumab and 21 % (95 % CI 20.3-21.7 %) in infliximab. Adalimumab and infliximab were associated with a higher risk of dose escalation relative to etanercept. There were no significant differences in the dose reduction percentages for the whole group of patients between treatments. In rheumatoid arthritis, etanercept is associated with a significantly lower percentage of dose-escalated patients and a lower magnitude of dose modification. Significant differences in the dose reduction between anti-TNF drugs evaluated were not observed.
authors: Pharmacy Service, Clinic University Hospital, Avda Blasco Ibáñez, 17, 46010, Valencia, Spain, ferriols.raf@gmail.com.
authors: Rafael
authors: R
authors: Ferriols-Lisart
authors: Francisco
authors: F
authors: Ferriols-Lisart
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D001688:Biological Products / Q000008:administration & dosage* / Q000009:adverse effects; D016009:Chi-Square Distribution; D054796:Drug Dosage Calculations; D006801:Humans; D016017:Odds Ratio; D012307:Risk Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D001688:Biological Products; D014409:Tumor Necrosis Factor-alpha
references: Ann Pharmacother. 2005 Dec;39(12):2021-5
references: 16288073
references: J Med Econ. 2014 Jan;17(1):1-10
references: 24131136
references: Arthritis Rheum. 2010 Jan;62(1):22-32
references: 20039405
references: BMC Musculoskelet Disord. 2004 Oct 14;5(1):36
references: 15485582
references: Curr Med Res Opin. 2009 Feb;25(2):303-14
references: 19192975
references: BMC Musculoskelet Disord. 2011 Sep 19;12:204
references: 21929807
references: Ann Rheum Dis. 2007 Jul;66(7):921-6
references: 17301106
references: Clin Ther. 2009 Apr;31(4):825-35
references: 19446156
references: Arthritis Care Res (Hoboken). 2012 May;64(5):640-7
references: 22473918
references: Ann Rheum Dis. 2013 Feb;72(2):165-78
references: 23178294
references: J Manag Care Pharm. 2005 Jun;11(5):383-93
references: 15934797
references: Clin Exp Rheumatol. 2008 Jan-Feb;26(1):45-51
references: 18328146
references: J Med Econ. 2012;15(4):635-43
references: 22332705
references: Semin Arthritis Rheum. 2010 Aug;40(1):2-14.e1
references: 20674669
references: J Manag Care Spec Pharm. 2014 Mar;20(3):301-8
references: 24564810
references: Curr Med Res Opin. 2008 Aug;24(8):2229-40
references: 18577308
references: Ann Rheum Dis. 2013 Dec;72(12):1947-55
references: 23223420
references: Curr Med Res Opin. 2010 Jul;26(7):1637-45
references: 20429830
references: Arthritis Care Res (Hoboken). 2010 Sep;62(9):1335-41
references: 20506128
references: Int J Epidemiol. 2007 Jun;36(3):666-76
references: 17470488
references: Arch Intern Med. 2006 Jan 9;166(1):57-63
references: 16401811
references: Rheumatology (Oxford). 2009 Mar;48(3):243-5
references: 19106164
references: Curr Med Res Opin. 2013 May;29(5):561-8
references: 23489410
references: Ther Drug Monit. 2013 Oct;35(5):588-94
references: 23942545
references: J Manag Care Pharm. 2004 Nov-Dec;10(6):538-42
references: 15548126
references: Ann Rheum Dis. 2008 Sep;67(9):1229-34
references: 18174220
references: Reumatol Clin. 2010 Jan-Feb;6(1):23-36
references: 21794674
references: CMAJ. 2009 Nov 24;181(11):787-96
references: 19884297
references: Am J Health Syst Pharm. 2010 Aug;67(15):1281-7
references: 20651319
references: Arthritis Rheum. 2011 Apr;63(4):877-83
references: 21452312
references: JAMA. 2000 Apr 19;283(15):2008-12
references: 10789670
references: BMC Musculoskelet Disord. 2008 Apr 17;9:52
references: 18419803
references: Rheumatology (Oxford). 2007 Mar;46(3):529-32
references: 17012439
references: BMJ. 2003 Sep 6;327(7414):557-60
references: 12958120
references: Ann Rheum Dis. 2004 Apr;63(4):426-30
references: 15020338
references: Scand J Rheumatol. 2007 Nov-Dec;36(6):418-23
references: 18092261
references: J Rheumatol. 2004 Aug;31(8):1538-45
references: 15290732
references: Rheumatology (Oxford). 2005 Dec;44 Suppl 4:iv18-iv22
references: 16306476
references: Ann N Y Acad Sci. 2009 Sep;1173:837-46
references: 19758236
references: Curr Med Res Opin. 2012 Apr;28(4):569-80
references: 22236091
references: J Rheumatol. 2009 May;36(5):907-13
references: 19332636
references: Clin Exp Rheumatol. 2011 Jan-Feb;29(1):26-34
references: 21345289
references: Clin Exp Rheumatol. 2013 Jul-Aug;31(4):559-65
references: 23710583
references: Manag Care Interface. 2004;Suppl A:5-8
references: 15198423
references: Clin Rheumatol. 2008 Aug;27(8):1049-52
references: 18463934
references: PLoS One. 2012;7(1):e30275
references: 22272322
references: J Med Econ. 2012;15(2):264-75
references: 22115327
references: Clin Ther. 2008 Jul;30(7):1375-84
references: 18691998
references: J Clin Epidemiol. 2009 Oct;62(10):e1-34
references: 19631507
references: Rheumatology (Oxford). 2011 Aug;50(8):1445-52
references: 21427177
references: Arthritis Rheum. 2005 Dec 15;53(6):872-8
references: 16342095
references: Reumatismo. 2011 Mar;63(1):18-28
references: 21509346
references: Adv Ther. 2013 May;30(5):517-27
references: 23740359
references: Pharmacotherapy. 2010 Apr;30(4):339-53
references: 20334454
references: Ann Rheum Dis. 2011 Mar;70(3):404-13
references: 21292833
references: Reumatol Clin. 2014 Jan-Feb;10 (1):10-6
references: 23876791
references: Ann Rheum Dis. 2007 Nov;66(11):1473-8
references: 17426065
references: Arthritis Rheum. 2006 Mar;54(3):711-5
references: 16508927
references: Arthritis Care Res (Hoboken). 2010 Mar;62(3):293-5
references: 20391473
references: Manag Care Interface. 2005 Apr;18(4):21-7
references: 15889759
references: Clin Ther. 2012 Dec;34(12):2286-92
references: 23153660
references: Am J Manag Care. 2003 Oct;9(6 Suppl):S136-43
references: 14577718