Dose Modification of Subcutaneous Tocilizumab in Patients with Rheumatoid Arthritis

TO THE EDITOR,

In their study published in American Health & Drug Benefits in December 2019, Punekar and colleagues analyzed US claims and electronic health record data and reported that more than 33% of patients with rheumatoid arthritis who initiated treatment with subcutaneous (SC) tocilizumab administered every other week, increased the dose to every-week dosing.¹

As the authors noted, according to the prescribing information approved by the US Food and Drug Administration, SC tocilizumab is administered every 2 weeks or every week, based on the patient’s weight and clinical response.^1,2 The authors conclude that this dose optimization of tocilizumab from every 2 weeks to every week “could result in increased economic burden.”¹

We acknowledge the authors’ efforts to analyze treatment patterns of patients receiving tocilizumab; however, the authors do not provide any data to support this conclusion. There are many factors that drive the direct and indirect costs related to biologic therapy use in patients with rheumatoid arthritis; the frequency of drug administration is only one component of direct costs. Other factors include concomitant treatment for rheumatoid arthritis, the number of previous treatments, adverse events, and inadequate or suboptimal response to treatment.^3-5 Indirect costs, such as low productivity, lost wages, and caregiver burden, also contribute to the increased economic burden.⁶

In their study, Punekar and colleagues did not evaluate the economic burden associated with tocilizumab alone or in comparison with other biologic drugs. Inadequate response to rheumatoid arthritis treatment has been shown to be associated with increased costs in patients with rheumatoid arthritis.³ Multiple studies have demonstrated greater persistence with tocilizumab compared with other biologics.^7-11

The ability to optimize biologic drug dosing to achieve treatment targets provides patients and physicians with more flexibility and therapy options, which can potentially reduce the costs of care. In addition, dose optimization allows physicians to adapt to the clinical needs of the patient. Accordingly, we believe that the authors’ conclusion that an increased dose frequency of tocilizumab may increase economic burden is not supported by the data.

Sincerely,

Jennie H. Best, PhD
Ibrahim Abbass, RPh, PhD
Lenore Tominna, PharmD
William Reiss, PharmD
Genentech, Inc., South San Francisco, CA
All the authors are employees and shareholders of ­Genentech.

1. Punekar R, Choi J, Boklage S, et al. Real-world dose modification patterns of subcutaneous tocilizumab among patients with rheumatoid arthritis. Am Health Drug Benefits. 2019;12(8):400-409.
2. Actemra (tocilizumab) injection, for intravenous or subcutaneous use [prescribing information]. South San Francisco, CA: Genentech; June 2019.
3. Strand V, Tundia N, Song Y, et al. Economic burden of patients with inadequate response to targeted immunomodulators for rheumatoid arthritis. J Manag Care Spec Pharm. 2018;24:344-352.
4. Hresko A, Lin TC, Solomon DH. Medical care costs associated with rheumatoid arthritis in the US: a systematic literature review and meta-analysis. Arthritis Care Res (Hoboken). 2018;70:1431-1438.
5. Best JH, Kong AM, Lenhart GM, et al. Association between glucocorticoid exposure and healthcare expenditures for potential glucocorticoid-related adverse events in patients with rheumatoid arthritis. J Rheumatol. 2018;45:320-328.
6. Birnbaum H, Pike C, Kaufman R, et al. Societal cost of rheumatoid arthritis patients in the US. Curr Med Res Opin. 2010;26:77-90.
7. Best J, Tominna L, Abbass I. Comparison of real-world persistence of subcutaneously administered biologic disease-modifying antirheumatic drug therapies among patients with rheumatoid arthritis switching from another biologic. Arthritis Rheumatol. 2019;71(suppl 10). Abstract 1427.
8. Ebina K, Hashimoto M, Yamamoto W, et al. Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis - the ANSWER cohort study-. PLoS One. 2018;13:e0194130. doi.org/10.1371/journal.pone.0194130.
9. Gottenberg JE, Morel J, Perrodeau E, et al; for the French Society of Rheumatology and the investigators participating in AIR, ORA, and REGATE registries. Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors: prospective cohort study. BMJ. 2019;364:l67. doi.org/10.1136/bmj.l67.
10. Lauper K, Nordström DC, Pavelka K, et al. Comparative effectiveness of tocilizumab versus TNF inhibitors as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs in patients with rheumatoid arthritis after the use of at least one biologic disease-modifying antirheumatic drug: analyses from the pan-European TOCERRA register collaboration. Ann Rheum Dis. 2018;77:1276-1282.
11. Lauper K, Mongin D, Iannone F, et al. Comparative effectiveness of TNF inhibitors and tocilizumab with and without conventional synthetic disease-modifying antirheumatic drugs in a pan-European observational cohort of bio-naïve patients with rheumatoid arthritis. Semin Arthritis Rheum. 2020;50:17-24.

THE AUTHORS RESPOND:

We thank Dr Best and her colleagues for their interest in our recently published study¹ and appreciate the opportunity to clarify the issues that were raised.

We agree with our colleagues that “there are many factors that drive the direct and indirect costs related to biologic therapy use in patients with rheumatoid arthritis.” Having said that, the evaluation of the economic burden associated with subcutaneous (SC) tocilizumab dose escalation was not the objective of the study. The main objective of the study, as stated in the article, was to understand the real-world dose modification patterns of SC tocilizumab in the treatment of patients with rheumatoid arthritis in the United States.

Therefore, in the discussion section of the article, we have clearly stated that “the impact of SC tocilizumab dose escalation on costs was not formally examined in our study”, and we suggested an examination of the economic implications of SC tocilizumab dose escalation as a potential area for future research.

Given the direct drug cost increases associated with dose escalation of SC tocilizumab, previous literature on the economic implications of dose escalation,^2,3 and expressed need for further study in this area, we believe that an appropriate characterization of the research and conclusions have been provided.

Sincerely,

Rajeshwari Punekar, MPH, PhD, Sanofi, Bridgewater, NJ
Jeannie Choi, PharmD, Independent Researcher, MD
Susan H. Boklage, MS, MPH, Regeneron Pharmaceuticals
Melitza Iglesias-Rodriguez, MD, Tarrytown, NY
Kamala Nola, PharmD, MS, Lipscomb College of Pharmacy, Nashville, TN

1. Punekar R, Choi J, Boklage S, et al. Real-world dose modification patterns of subcutaneous tocilizumab among patients with rheumatoid arthritis. Am Health Drug Benefits. 2019;12(8):400-409.
2. Nadkarni A, McMorrow D, Patel C, et al. Incidence of dose escalation and impact on biologic costs among patients with rheumatoid arthritis treated with three intravenous agents. J Comp Eff Res. 2017;6:671-682.
3. Garces K, Thorne C, Boire G, et al. Comparison of dose escalation and costs of dose escalation between patients with rheumatoid arthritis initiating biologic treatment with etanercept, adalimumab, or infliximab. Value Health. 2016;19:A229-A230. Abstract PMS29.