Stanley B Cohen1, Joel M Kremer2,3, Kimberly J Dandreo3, George W Reed3, Robert Magner4, Ying Shan3, Shelly Kafka5, Raphael J DeHoratius5,6, Lorie Ellis5, Dennis Parenti5. 1. Metroplex Clinical Research Center, 8144 Walnut Hill Lane, Suite 800, Dallas, TX, 75231, USA. arthdoc@aol.com. 2. The Center for Rheumatology, Albany Medical College, 4 Tower Place, 8th Floor, Albany, NY, 12203, USA. 3. Corrona, LLC, 1440 Main Street, Suite 310, Waltham, MA, 02451, USA. 4. University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA, 01655, USA. 5. Janssen Scientific Affairs, LLC, 800 Ridgeview Drive, Horsham, PA, 19044, USA. 6. Sidney Kimmel School of Medicine, Thomas Jefferson University, 1025 Walnut Street #100, Philadelphia, PA, 19107, USA.
Abstract
INTRODUCTION: Dose escalation of infliximab in both primary and secondary nonresponders is widely reported; however, the usefulness of dose escalation has been disputed. The objective of this analysis is to evaluate trends in clinical efficacy following multiple infliximab dose escalations in patients with rheumatoid arthritis (RA). METHODS: Patients enrolled in a US RA registry were included if they initiated infliximab at 3 mg/kg every 8 weeks, received ≥ 1 infliximab dose escalation within 12 months of initiation, and had ≥ 1 visit following dose escalation. Trends in mean Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores from visits following dose escalations were evaluated. RESULTS: In patients who received 2 or 3 dose escalations, the initial (1 or 2) dose escalations resulted in reduced mean CDAI scores, but subsequent escalations did not further reduce disease activity. In patients who received ≥ 4 dose escalations, mean CDAI scores did not further reduce disease activity over time. Mean HAQ scores were stable over time in patients who received 2 or 3 dose escalations. In patients who received ≥ 4 dose escalations, mean HAQ scores decreased following 1 dose escalation but progressively increased following subsequent dose escalations. CONCLUSION: Initial dose escalations (from 3 mg/kg to the equivalent of approximately 5 to 7 mg/kg) may be useful in controlling disease activity; however, there may be diminishing clinical benefit of further escalations, which can also increase the potential risk for infection and increase incremental drug costs. KEY POINTS: • Initial infliximab dose escalations (1 to 2) may be useful in lowering disease activity in patients with rheumatoid arthritis. • There does not appear to be a clinical benefit in infliximab dose escalations above the equivalent of 5 to 7 mg/kg.
INTRODUCTION: Dose escalation of infliximab in both primary and secondary nonresponders is widely reported; however, the usefulness of dose escalation has been disputed. The objective of this analysis is to evaluate trends in clinical efficacy following multiple infliximab dose escalations in patients with rheumatoid arthritis (RA). METHODS:Patients enrolled in a US RA registry were included if they initiated infliximab at 3 mg/kg every 8 weeks, received ≥ 1 infliximab dose escalation within 12 months of initiation, and had ≥ 1 visit following dose escalation. Trends in mean Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores from visits following dose escalations were evaluated. RESULTS: In patients who received 2 or 3 dose escalations, the initial (1 or 2) dose escalations resulted in reduced mean CDAI scores, but subsequent escalations did not further reduce disease activity. In patients who received ≥ 4 dose escalations, mean CDAI scores did not further reduce disease activity over time. Mean HAQ scores were stable over time in patients who received 2 or 3 dose escalations. In patients who received ≥ 4 dose escalations, mean HAQ scores decreased following 1 dose escalation but progressively increased following subsequent dose escalations. CONCLUSION: Initial dose escalations (from 3 mg/kg to the equivalent of approximately 5 to 7 mg/kg) may be useful in controlling disease activity; however, there may be diminishing clinical benefit of further escalations, which can also increase the potential risk for infection and increase incremental drug costs. KEY POINTS: • Initial infliximab dose escalations (1 to 2) may be useful in lowering disease activity in patients with rheumatoid arthritis. • There does not appear to be a clinical benefit in infliximab dose escalations above the equivalent of 5 to 7 mg/kg.
Authors: Jaclyn Anderson; Liron Caplan; Jinoos Yazdany; Mark L Robbins; Tuhina Neogi; Kaleb Michaud; Kenneth G Saag; James R O'Dell; Salahuddin Kazi Journal: Arthritis Care Res (Hoboken) Date: 2012-05 Impact factor: 4.794
Authors: V F Schabert; B Bruce; C F Ferrufino; D R Globe; D J Harrison; B Lingala; J F Fries Journal: Curr Med Res Opin Date: 2012-03-06 Impact factor: 2.580
Authors: D E Furst; E C Keystone; J Braun; F C Breedveld; G R Burmester; F De Benedetti; T Dörner; P Emery; R Fleischmann; A Gibofsky; J R Kalden; A Kavanaugh; B Kirkham; P Mease; J Sieper; N G Singer; J S Smolen; P L C M Van Riel; M H Weisman; K Winthrop Journal: Ann Rheum Dis Date: 2011-03 Impact factor: 19.103
Authors: Maxine D Fisher; Crystal Watson; Kathleen M Fox; Yen-Wen Chen; Shravanthi R Gandra Journal: Curr Med Res Opin Date: 2013-04-03 Impact factor: 2.580
Authors: Mahboob U Rahman; Ingrid Strusberg; Piet Geusens; Alberto Berman; David Yocum; Daniel Baker; Carrie Wagner; John Han; Rene Westhovens Journal: Ann Rheum Dis Date: 2007-03-28 Impact factor: 19.103
Authors: Ruediger B Mueller; Hendrik Schulze-Koops; Daniel E Furst; Stanley B Cohen; Kenneth Kwok; Lisy Wang; Tim Killeen; Johannes von Kempis Journal: Clin Rheumatol Date: 2022-01-01 Impact factor: 2.980