Longitudinal clinical outcomes after the escalation of subcutaneous tocilizumab from every 2 weeks to once weekly in rheumatoid arthritis with inadequate disease control: A 52-week real-world observational study

To describe 52-week longitudinal clinical outcomes after escalation of subcutaneous tocilizumab (TCZ-SC) from every 2 weeks (Q2W) to once weekly (Q1W) in rheumatoid arthritis (RA) patients with inadequate clinical control during Q2W dosing, and contextualize findings using a TCZ-SC Q2W continuation cohort. This single-center retrospective observational study included 58 patients with RA who escalated from TCZ-SC Q2W to Q1W. The primary outcome was the overall longitudinal change in the Clinical Disease Activity Index (CDAI) through week 52, assessed using a complete-case Friedman test. Linear mixed-effects models using all available observations were fitted as sensitivity analyses. Secondary analyses included the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR), matrix metalloproteinase-3 (MMP-3), laboratory safety and renal outcomes, re-adjudicated difficult-to-treat (D2T) RA status, follow-up disposition, individual-level concomitant treatment intensification, and a Q2W continuation contextual comparison. The median CDAI decreased from 16.00 at Q1W escalation to 8.20 at week 52 (complete-case Friedman test, n = 42, P < 0.001). In mixed-effects sensitivity analyses, model-estimated week-52 changes were − 5.89 points for CDAI (95% CI, − 8.15 to − 3.63), − 1.29 points for DAS28-ESR (95% CI, − 1.63 to − 0.95), − 45.8% for MMP-3 (95% CI, − 54.9% to − 34.7%), and − 4.79 mL/min/1.73 m2 for estimated glomerular filtration rate (eGFR) (95% CI, − 7.65 to − 1.92). Five patients (8.6%) fulfilled the stricter D2T RA definition. Fifteen patients lacked week-52 CDAI data because of Q1W discontinuation or interruption (n = 13) or transfer of care (n = 2); the incomplete follow-up group had higher baseline disease activity. Seven patients had documented regular systemic treatment intensification during weeks 0–12; after excluding them, the median 12-week ΔCDAI remained − 3.00 (P < 0.001). In the exploratory 12-week comparison, the median ΔCDAI was − 2.85 in the Q1W escalation cohort and − 3.40 in the Q2W residual-activity subgroup, with no significant between-group difference (P = 0.754). No serious infections or treatment discontinuations due to adverse events were documented. Disease activity decreased after Q1W escalation, with directionally consistent sensitivity analyses. However, the 12-week CDAI changes did not differ significantly between the Q1W escalation cohort and the Q2W residual-activity subgroup. These descriptive findings do not establish an incremental or causal benefit of Q1W escalation. • In selected patients with RA, CDAI decreased over 52 weeks after escalation from TCZ-SC Q2W to Q1W, with directionally consistent results in mixed-effects sensitivity analyses. • Individual-level re-adjudication of D2T RA status emphasized the importance of distinguishing dose escalation within the same drug from failure of distinct b/tsDMARD mechanisms. • An exploratory 12-week comparison showed no significant difference in ΔCDAI between the Q1W escalation cohort and the Q2W residual-activity subgroup; an incremental or causal benefit of Q1W escalation was not established.