AB0203 EFFECT OF DOSE ESCALATION OF SUBCUTANEOUS TOCILIZUMAB ON DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS IN A RANDOMIZED CONTROLLED TRIAL
Authors: N. Singer, S. Mohan, J. Han, M. Edwardes, M. Michalska
Journal: Annals of the Rheumatic Diseases (2021)

Background: In patients with RA, subcutaneous tocilizumab (TCZ-SC) is administered every 2 weeks (q2w) or every week (qw), based on the patient’s weight and clinical response. Objectives: To compare the effects on disease activity at week 24, when the dosing schedule of TCZ-SC was escalated from q2w to qw, in patients who did not achieve LDA (DAS28-ESR &gt; 3.2) at week 12 in COMP-ACT with patients who, despite not achieving LDA, continued TCZ-SC qw in SUMMACTA and q2w in BREVACTA. Methods: US patients in COMP-ACT who weighed &lt; 100 kg at baseline and who received TCZ-SC 162 mg q2w + methotrexate escalated to qw if they did not achieve LDA at week 12. DAS28-ESR remission (&lt; 2.6) and LDA (≤ 3.2), CDAI remission (≤ 2.8) and LDA (≤ 10) and SDAI remission (≤ 3.3) and LDA (≤ 11) at week 24 were compared between patients who switched from q2w to qw and North American patients in SUMMACTA who initiated TCZ qw + csDMARDs and continued a qw dose (baseline body weight &lt; 100 kg and DAS28 &gt; 3.2 at week 12). A secondary analysis compared COMP-ACT patients who escalated from q2w to qw with all SUMMACTA patients who continued a qw dose and all BREVACTA patients who initiated a TCZ-SC q2w dose + csDMARDs and continued a q2w dose (baseline body weight &lt; 100 kg and DAS28 &gt; 3.2 at week 12). DAS28 was standardized to DAS28-ESR, and comparisons were calculated using a mixed model with repeated-measures logistic regression, including the following covariates: CDAI, SDAI and/or DAS28 at the reference visit (week 12), as well as study baseline values of CDAI, SDAI and/or DAS28, baseline age, sex, TNFi use prior to the study (yes or no) and weight category. Results: A total of 328 US patients in COMP-ACT did not achieve LDA at week 12 and escalated from q2w to qw TCZ-SC. In SUMMACTA, 285 patients did not achieve LDA at week 12 and continued TCZ-SC qw, of whom 71 were from North America. Baseline demographic and clinical characteristics were comparable between patients in COMP-ACT and North American patients in SUMMACTA. A significantly higher proportion of patients in COMP-ACT achieved DAS28-ESR, CDAI and SDAI remission and LDA 12 weeks after TCZ dose escalation (week 24) than North American SUMMACTA patients (Table 1). Similar results were seen when the proportion of patients who achieved DAS28 remission and LDA was compared at week 24 between patients in COMP-ACT and patients from all geographic regions who did not escalate dosing in SUMMACTA and BREVACTA (N=196). Conclusion: US patients with RA who did not achieve LDA and escalated from q2w to qw TCZ-SC at week 12 in COMP-ACT had better disease activity outcomes at week 24 than North American patients who did not achieve LDA and continued qw dosing in SUMMACTA. These results provide some evidence that escalation from q2w to qw has more effect than expected without dose change for patients who do not achieve LDA by week 12. Table 1. Comparison at Week 24 of Clinical Response After Week 12 Dose Escalation or Continuation Between Patients Who Did Not Achieve LDA at Week 12 All COMP-ACT (N = 328 ) North American SUMMACTA (n = 71 ) All SUMMACTA (N = 285 ) All BREVACTA (N = 196 ) DAS28-ESR remission, n (%) 66 (20.1) 7 (9.9) 44 (15.4) 36 (18.4) Adjusted OR (95% CI) Ref 5.76 (1.92, 17.32) 3.29 (2.11, 5.12) 2.35 (1.44, 3.84) P value Ref 0.0018 &lt; 0.0001 0.0006 DAS28-ESR LDA, n (%) 122 (37.2) 17 (23.9) 90 (31.6) 60 (30.6) Adjusted OR (95% CI) Ref 3.36 (1.61, 7.00) 2.81 (1.97, 4.01) 2.24 (1.50, 3.33) P value Ref 0.0012 &lt; 0.0001 &lt; 0.0001 CDAI remission, n (%) 12 (3.7) 2 (2.8) 13 (4.6) 11 (5.6) Adjusted OR (95% CI) Ref 4.50 (1.32, 15.32) 2.93 (1.37, 6.27) 1.45 (0.69, 3.05) P value Ref 0.0161 0.0056 0.3325 CDAI LDA, n (%) 80 (24.4) 11 (15.5) 81 (28.4) 66 (33.7) Adjusted OR (95% CI) Ref 4.19 (1.88, 9.35) 2.35 (1.63, 3.39) 1.32 (0.88, 1.97) P value Ref 0.0005 &lt; 0.0001 0.1825 SDAI remission, n (%) 16 (4.9) 2 (2.8) 15 (5.3) 11 (5.6) Adjusted OR (95% CI) Ref 5.23 (1.44, 19.01) 3.23 (1.54, 6.76) 1.64 (0.81, 3.30) P value Ref 0.0120 0.0019 0.1670 SDAI LDA, n (%) 89 (27.1) 11 (15.5) 91 (31.9) 72 (36.7) Adjusted OR (95% CI) Ref 4.68 (2.20, 9.99) 2.20 (1.56, 3.11) 1.47 (0.99, 2.17) P value Ref &lt; 0.0001 &lt; 0.0001 0.0540 Acknowledgements: This study was funded by Genentech, Inc. Support for third-party writing assistance, furnished by Health Interactions, Inc., was provided by Genentech, Inc. Disclosure of Interests: Nora Singer Grant/research support from: Genentech/Roche, Merck and Pfizer, Shalini Mohan Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Jian Han Shareholder of: Genentech, Inc., Employee of: Genentech, Inc., Michael Edwardes Employee of: Everest Clinical Research, Margaret Michalska Shareholder of: Genentech, Inc., Employee of: Genentech, Inc.