Outcomes of infliximab dose escalation in patients with rheumatoid arthritis
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).
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.
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.
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.
• 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.
KeywordsDose escalation Infliximab Patient registry Rheumatoid arthritis
Writing support was provided by Holly Capasso-Harris, PhD, of Synchrogenix, a Certara Company, Wilmington, DE. This study was sponsored by Corrona, LLC, and the analysis and medical writing support were funded by Janssen Scientific Affairs, LLC, Spring House, PA. Corrona, LLC, Waltham, MA, has been supported through contracted subscriptions in the last 2 years by AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Crescendo, Eli Lilly and Company, Genentech, Gilead, GlaxoSmithKline, Horizon Pharma USA, Janssen, Momenta Pharmaceuticals, Novartis, Pfizer Inc., Roche, Sun-Merck, UCB, and Valeant.
Compliance with ethical standards
All study participants provided written informed consent. Institutional Review Board (IRB) approvals for this study were obtained from a central IRB (New England IRB, Needham, Massachusetts, USA; IRB registration number 120160610) for private practice sites and local IRBs of participating academic sites.
Conflict of interest
Dr. Cohen has served as an investigator and consultant for Amgen, AbbVie, Janssen, Genentech, Pfizer, Merck, Bristol-Myers Squibb, and Roche (less than $10,000 each). Dr. Kremer is employed by and has equity interest in Corrona, LLC, and has served as a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Gilead, GSK, Eli Lilly and Company, Genentech, Medimmune, Sanofi, and Pfizer Inc. (less than $10,000 each) and an investigator for AbbVie, Genentech, Eli Lilly and Company, Novartis, and Pfizer Inc. (less than $10,000 each). Ms. Dandreo is employed by Corrona, LLC. Dr. Reed is employed by and has stock ownership in Corrona, LLC. Mr. Magner is employed by Corrona, LLC. Dr. Shan is employed by Corrona, LLC. Dr. Kafka is employed by and has stock ownership in Johnson and Johnson. Dr. DeHoratius was employed by (at the time the work was conducted) and has stock ownership in Johnson and Johnson. Dr. Ellis is employed by and has stock ownership in Johnson and Johnson. Dr. Parenti was employed by (at the time the work was conducted) and has stock ownership in Johnson and Johnson.
The authors have full control of all primary data. Corrona dataset is based on a large US multicenter study adhering to a number of institutional review boards, with complex logistics. Patients did not provide consent to raw data sharing during the data collection for this purpose, and the Corrona data sharing policies do not permit raw data sharing for this purpose. An aggregated limited dataset from the current analyses is available to qualified investigators with an approved protocol. Data requests may be sent to Corrona, represented by Dr. Leslie Harrold, email email@example.com.
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