SAT0183 Clinical remission in subjects with rheumatoid arthritis treated with subcutaneous tocilizumab as monotherapy or in combination with methotrexate or other synthetic dmards: a real-world clinical trial (tospace)

• Published in: Annals of the rheumatic diseases Vol. 76; no. Suppl 2; p. 840
• Main Authors: Sanmarti, R, Mola, E Martín, Fonseca, JE, Veale, DJ, Escudero, A, González, C
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 01.06.2017
• Subjects: Clinical trials; Drug development; Immunosuppressive agents; Intolerance; Methotrexate; Monoclonal antibodies; Patients; Remission; Rheumatoid arthritis
• DOI: 10.1136/annrheumdis-2017-eular.4951
• ISSN: 0003-4967

BackgroundSubcutaneous tocilizumab (TCZ-SC) has demonstrated non-inferiority to TCZ-IV and superiority to placeboObjectivesThe primary objective of this study was to assess the 24-week efficacy and safety of subcutaneous (SC) tocilizumab (TCZ) 162 mg weekly (qw) as monotherapy or in combination with methotrexate (MTX) or other synthetic (s) DMARDs in patients with active rheumatoid arthritis (RA) in the real world settingMethodsThis multinational (Spain, Ireland, Portugal), multicenter, phase IIIb study. Subjects ≥18 years of age with active RA (DAS 28-ESR >3.2) who have had inadequate response or intolerance to sDMARDs or to a first anti-TNF drug. The study comprised a phase 1 with open-label design in which patients received TCZ-SC 162 mg qw (+/- oral/SC MTX or other sDMARDs) for 24-weeks and the main outcome was the percentage of patients achieving sustained clinical remission (DAS 28-ESR <2.6) at Week 20 and Week 24 (primary outcome of the study); and a phase 2 where patients achieving sustained clinical remission during the phase 1 were randomized to receive TCZ-SC 162 mg qw or TCZ-SC 162 mg q2w (+/- oral/SC MTX or other sDMARDs) for an additional 24 weeks; the main outcome of the phase 2 was the percentage of patients who maintained the remission at week 48 (i.e. DAS 28-ESR<2.6)Results401 patients were included in the phase 1, 74 patients received TCZ-SC monotherapy and 327 patients received TCZ-SC in combination with oral/SC MTX or other sDMARDs. Sustained clinical remission rates were comparable between the mono- and combination-therapy groups at 24 week (48.4% vs. 52.9%, p=0.523). Of the 179 patients who achieved sustained clinical remission during the phase 1, 89 were randomly assigned to receive TCZ-SC 162 mg qw and 90 to receive TCZ-SC 162 mg q2w. At the end of phase 2, the percentage of patients who maintained the remission at week 48 was 91.5% with TCZ-SC qw and 73.9% with TCZ-SC q2w (p=0.002). Main efficacy outcomes for both phases of the study are presented in the table. Rates of serious adverse events (AEs) and rates of AEs leading to drug discontinuation were similar in patients treated with mono or combination therapy, and in patients treated with TCZ-SC qw or TCZ-SC q2w.Phase 1 – OutcomeTCZ-SC monotherapyTCZ-SC Combinationp-value N=74N=327 Sustained clinical remission, %48.452.90.523ACR20, %79.783.30.495ACR50, %59.458.70.923ACR70, %40.637.70.666ACR90, %23.416.70.207HAQ-DI (baseline/24 weeks), mean1.49/0.851.36/0.82NSPhase 2 – OutcomeTCZ-SC 162 mg qwTCZ-SC 162 mg q2wN=89N=90p-valueClinical remission, %91.573.90.002ACR20, %96.488.80.056ACR50, %88.179.80.766ACR70, %71.465.20.377ACR90, %45.232.60.088Mean change in DAS28-0.020.350.037ConclusionsIn the real world setting, treatment with TCZ-SC 162 mg weekly in patients with active RA is associated with rate of sustained clinical remission of approximately 50% regardless it is administered as monotherapy or in combination with a sDMARD. The proportion of patients who remained in clinical remission at week 48 was significantly higher with TCZ-SC qw than with TCZ-SC q2w. The safety profile of TCZ-SC was consistent with previous studies of TCZ-SC and TCZ-IVDisclosure of InterestR. Sanmarti Grant/research support from: Roche, E. Martín Mola Grant/research support from: Roche, J. Fonseca Grant/research support from: Roche, D. Veale Grant/research support from: Roche, A. Escudero Grant/research support from: Roche, C. González Grant/research support from: Roche