ADALIMUMAB DOSE ESCALATION IN THE IMPROVED COHORT DOES NOT IMPROVE SHORT-TERM OUTCOMES

Background: In rheumatoid arthritis (RA), anti-TNF dose escalation is reportedly applied in up to 10% of patients in real world settings.[1] Yet, clinical data on its efficacy are scarce and are limited mostly to dose variations in infliximab. In the EULAR and ACR treatment recommendations it is advised to switch to another mode of action after failure of a bDMARD, and dose escalation is not mentioned. Objectives: To investigate the short-term effect on DAS and HAQ of dose escalation of adalimumab in patients with an insufficient response to normal dosed adalimumab, compared to patients not treated with dose escalation. Methods: In the IMPROVED study, 479 RA patients (2010-criteria) started treatment with MTX and a tapered high dose of prednisone bridging and were treated to target (remission, DAS<1.6). If this was not achieved, patients received adalimumab (ADA) 40 mg/2 weeks with MTX, either immediately after a randomization step at t=4 months, or as delayed treatment at any treatment visit with DAS≥1.6 in the other randomization arm, which constituted treatment with MTX + hydroxychloroquine + sulfasalazine + continued low dose prednisone (csDMARD combo). If after 4 months treatment with ADA 40 mg/2 weeks and MTX remission was still not achieved, patients were required to double the ADA dose to 40mg/week. We compared the effect on DAS and HAQ between patients who had, or due to protocol violation had not received the double ADA dose at 4 months after (potential) doubling of ADA. Results: During the trial, in total 215 patients ever received ADA, 63 immediately at the 4-month study visit, the others later during the trial. Of these 215 patients, 131 were not in remission after their first ADA treatment; 62 patients received a double ADA dose thereafter (DD group). Despite not achieving DAS-remission on 40 mg/2 weeks, 69 patients were not treated with double dosed ADA (nonDD group). Instead, 30 continued ADA without dose change, of which 10 who had not previously used MTX with ADA (due to protocol violation) and now added MTX, 11 changed the dose of MTX but not of ADA, and 18 stopped ADA. Baseline characteristics of the DD and nonDD group were similar (Table 1). Median (IQR) DAS at the timepoint of required dose doubling was 2.40 (1.97; 2.92) in the DD group and 2.31 (1.83; 2.65) in the nonDD group (p=0.09), and median (IQR) HAQ was 1.00 (0.5; 1.4) and 0.88 (0.5; 1.4), respectively (p=0.70). Follow up data for the next study visits were available for 58 patients in the DD and 61 in the nonDD group. Median (IQR) deltaDAS was -0.51 (-0.96; -0.04) in the DD group and -0.22 (-0.77; 0.21) in the nonDD group (p=0.06), with 18/58 (31%) and 26/61 (43%), respectively, achieving DAS remission at that point (p=0.36). Median HAQ change was 0 (-0.38; 0.25) in the DD group and 0 (-0.25; 0.13) in the nonDD group (p=0.82). In the nonDD group, 29% of patients who stopped ADA (instead of doubling) achieved remission (median deltaDAS -0.13), 48% of patients who did not change any medication achieved remission (median deltaDAS -0.34) and 44% of patients who added a csDMARD to ADA achieved remission after 4 months (median deltaDAS -0.77, Table 2). In the DD group, 29% of patients who (in addition to doubling ADA) added a csDMARD to previous ADA monotherapy achieved remission after 4 months (median [IQR] deltaDAS -0.66 [-0.99; -0.11]), this was the same in patients with MTX+ADA who doubled their ADA dose (median [IQR] deltaDAS -0.46 [-0.97; 0.04]). Conclusion: In patients with early RA who did not achieve DAS remission on adalimumab 40 mg/2 weeks, we found no significant difference in clinical response between those who according to trial protocol doubled the ADA dose, and those who did not change the dose or even discontinued ADA as protocol violation. REFERENCES: [1] Ferriols-Lisart R, Ferriols-Lisart F. Dose modifications of anti-TNF drugs in rheumatoid arthritis patients under real-world settings: a systematic review. Rheumatol Int. 2015;35(7):1193-210. Acknowledgements: NIL. Disclosure of Interests: Cornelia F. Allaart The study was designed by the investigators and financially supported by Abbott. Data collection, trial management, data collection, data analysis and preparation of the manuscript were performed by the authors., Joy van der Pol: None declared, Sytske Anne Bergstra Speaker fee from Benecke, ASPIRE grant from Pfizer, Tom Huizinga: None declared. DOI: 10.1136/annrheumdis-2024-eular.4985 Keywords: Biological DMARD, Clinical Trial Citation: , volume 83, supplement 1, year 2024, page 837Session: Rheumatoid arthritis (Poster View)

Biological DMARD, Clinical Trial