Infliximab efficacy in rheumatoid arthritis after an inadequate response to etanercept or adalimumab: results of a target-driven active switch study

Abstract

Objective:

Evaluate efficacy of infliximab with response-driven dosing in patients with active RA.

Research design and methods:

Patients (n = 203) with active RA despite methotrexate + etanercept/adalimumab, participated in this active-infliximab-switch study. Infliximab 3 mg/kg was infused at Weeks 0, 2, 6, 14, and 22 with escalation to 5 or 7 mg/kg depending on EULAR response at Weeks 14 and 22. The primary endpoint was EULAR response at Week 10. Safety was assessed through Week 30. Infliximab levels and antibodies to infliximab (ATI) were measured at Weeks 0, 6, 14, and 26.

Clinical trial registration:

NCT 00714493, EudraCT 2007-003288-36.

Results:

Of 197 evaluable patients, 120/77 previously received etanercept/adalimumab. Baseline mean (SD) swollen and tender joint counts were 17.3 (10.54) and 30.2 (16.89), respectively; mean DAS28-ESR was 6.19 (0.981). At Week 10, 98 (49.7%; 95% CI: 42.6%, 56.9%) patients achieved EULAR response, with a significantly improved DAS28-ESR score (mean [SD] change −1.1 [1.15]; p < 0.001). EULAR response was achieved by 41.7%/62.3% of patients previously receiving etanercept/adalimumab (p = 0.006). At Week 26, 51.8% (95% CI: 44.6%, 58.9%) of patients achieved or maintained EULAR response. Infliximab dose was escalated in 100 patients, 52% of whom achieved EULAR response at Week 26. Median serum concentration levels at Week 26 showed that dose escalation helped EULAR non-responders achieve levels similar to or higher than the levels seen in responders. ATI were associated with lower serum concentrations of infliximab, consistent with lower efficacy rates among ATI-positive patients.

Conclusion:

Infliximab, in treat-to-target settings with individual dose escalation, demonstrated significant efficacy at Weeks 10 and 26 in patients switched to infliximab after inadequate response to etanercept/adalimumab. The observed efficacy indicated that the switch to infliximab and ability to increase dose in a targeted fashion were beneficial.

Key limitations:

Given the relatively short duration of study follow-up, these safety findings require confirmation in a longer-term study.

Keywords::

• Anti-infliximab antibodies
• Anti-TNF
• Efficacy
• Infliximab
• Rheumatoid arthritis

Transparency

Declaration of funding

This study was funded by Janssen Research & Development LLC and Merck/Schering Plough Research Institute Inc.

Declaration of financial/other relationships

R.F. has disclosed that he has received consulting fees and research grant support from Janssen. J.A.G. has disclosed that he has received consulting fees and/or research grants via the Atlanta Center for Clinical Research from Amgen, Astra Zeneca, Biogen-Idec, Janssen, Crescendo Bioscience, Genentech, Lilly, MEDI-IMUNE, Pfizer, and UCB. M.L.-R. has disclosed that she has received consulting fees from Janssen, Bristol-Myers-Squibb, MSD, and Roche. E.Z. has disclosed that she has received support from Janssen, Bristol-Myers-Squibb, Genentech, and Roche. H.E.-K. has disclosed that he has received consulting fees and research grant support from Janssen. R.B., R.D., J.W., and D.D. have disclosed that they were employees of Janssen Biotech Inc. at the time of this study. H.K. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial relationships to disclose.

Acknowledgments

The authors thank Sumesh Kalappurakal, Linda Tang PhD, and Dave Zelinger PhD (Janssen Scientific Affairs, LLC) for statistical support and Michelle Perate MS, Kirsten Schuck, and Mary Whitman PhD (Janssen Scientific Affairs, LLC) for writing support, in all cases funded by Janssen Biotech Inc. The authors also thank the following study investigators who enrolled patients into the trial: Aelion J (Jackson TN USA), Amital H (Kfar Saba Israel), Baerwald C (Leipzig Germany), Baraf H (Wheaton MD USA), Bensen W (Hamilton, ON, Canada), Bertin P (Limoges France), Burkhardt H (Frankfurt Germany), Carreno L (Madrid Spain), Cauza E (Vienna Austria), Chattopadhyay C (Wigan UK), Cohen S (Tyler TX USA), Diab I (Middleburg Heights OH USA), Edwards W (Charleston SC USA), El-Kadi H (Freehold NJ USA), Elkayam O (Tel Aviv Israel), Emery P (Leeds UK), Fleischmann R (Dallas TX USA), Forstot J (Boca Raton FL USA), Goldman J (Atlanta GA USA), Gomez Reino JJ (La Coruna Spain), Hackshaw K (Columbus OH USA), Halter D (Houston TX USA), Kellner H (Muenchen Germany), Keystone E (Toronto ON Canada), Khraishi M (St. John’s NF Canada), Kimmel S (Tamarac FL USA), Langevitz P (Tel Hashomer Israel), Lespessailles E (Orleans France), Lieberman E (Berkeley Heights NJ USA), Lowenstein M (Palm Harbor FL USA), Majjhoo A (St. Claire Shores MI USA), Mandel D (Mayfield Village OH USA), Miniter M (Rock Island IL USA), Moreta E (Eagan MN USA), Murphy F (Duncansville PA USA), Nascimento J (Bridgeport CT USA), Neal J (Lexington KY USA), Neeck G (Hohenfelde Germany), Nguyen P (Reston VA USA), Pando J (Lewes DE USA), Patel R (Ft. Worth TX USA), Pegram S (Houston TX USA), Peters E (Paradise Valley AZ USA), Queiro R (Oviedo Spain), Reitblat T (Ashkelon Israel), Riccardi P (Syracuse NY USA), Rosner I (Haifa Israel), Ross J (Allentown PA USA), Ross S (St. Louis MO USA), Schneider R (St. Louis MO USA), Shergy W (Huntsville AL USA), Singhal A (Mesquite TX USA), Stern M (Springfield IL USA), Stupi A (Wexford PA USA), Tahir H (London UK), Thurmond-Anderle M (Amarillo TX USA), Tishler M (Beer Yaakov Israel), Troum O (Santa Monica CA USA), Vaz B (Tucson AZ USA), Wade J (Vancouver BC Canada), Waller P (Houston TX USA), Wassenberg S (Ratingen Germany), Zanetakis E (Tulsa OK USA), Zisman D (Haifa Israel).

Notes

*Enbrel is a registered trade name of Amgen Inc. and Pfizer Inc., Thousand Oaks, CA, USA

†Remicade is a registered trade name of Janssen Biotech, Inc., Horsham, PA, USA

‡Humira is a registered trade name of Abbott Laboratories, North Chicago, IL, USA

§Cimzia is a registered trade name of UCB Inc., Smyrna, GA, USA

⊥Simponi is a registered trade name of Janssen Biotech Inc., Horsham, PA, USA