Background The TENDER clinical trial is a 3-part, 5-year, phase 3 study of intravenous tocilizumab (TCZ) in patients with active systemic juvenile idiopathic arthritis (sJIA). After 2 years of treatment on TCZ every 2 weeks (Q2W), sJIA patients who maintained clinically inactive disease (CID) status for 3 months were given the option to participate in an alternative TCZ dosing regimen aimed at spacing the infusions and eventually withdrawing TCZ.
Objectives To describe the clinical features and disease outcomes in patients who entered the optional alternative dosing schedule in the TENDER study.
Methods To qualify for the optional alternative dosing schedule, patients had to be in the study for a minimum of 2 years, had to achieve American College of Rheumatology JIA CID status, and had to be off oral glucocorticoids for 12 weeks before entry. Among the 112 patients enrolled, 39 (35%) entered the optional alternative dosing regimen. This entailed a staged prolongation of the interval between TCZ infusions from 2 weeks (standard interval) to 3 weeks (Q3W), then 4 weeks (Q4W), with the option of terminating TCZ after the discontinuation of NSAIDs and methotrexate (MTX; if patients were being treated with MTX).
Results Twenty-three male and 16 female patients entered the optional alternative dosing schedule by the end of the 5-year study. The mean characteristics of these patients at the start of TCZ treatment were as follows: active joints, 15.7; Physician Global VAS score, 62.7; CHAQ-DI score, 1.65; erythrocyte sedimentation rate, 55.5 mm/h; fever, 15 patients. Of the 39 patients, 19 lost CID status while on the alternative dosing schedule. In these 19 patients, the time to loss of CID status ranged from 1.5 to 25.3 months from initiation of the optional alternative dosing schedule (n=4 on Q3W dosing; n=10 on Q4W dosing; n=5 off TCZ). Risk for losing CID status on the optional alternative dosing schedule was 62.5% (10/16) in patients on concomitant MTX and 39.1% (9/23) in patients not on MTX. CID status was maintained in 20 of the 39 patients (51.2%) entering the optional alternative dosing schedule. Of the patients who maintained CID status at their last visit, 3 were on Q3W dosing, 9 were on Q4W dosing, and 8 were able to discontinue TCZ (range of time since discontinuation: 15.3-21.3 months). In total, 13 patients tapered off TCZ; of these, 8 maintained CID status and 5 lost CID status and returned to the 2-week dosing interval. One patient developed macrophage activation syndrome while on Q3W dosing after having been on this regimen for ∼7 weeks, for a rate of 2.1/100 patient-years (PY), which was not significantly higher than the 1.4/100 PY observed in the entire TENDER study (on Q2W dosing).
Conclusions Of the 35% of patients with sJIA in the TENDER study who entered the optional alternative dosing regimen, which allowed a decrease in the frequency of infusions of TCZ, approximately half were able to maintain inactive disease over an extended period of time.
Disclosure of Interest F. De Benedetti Grant/research support from: Roche, Novartis, Pfizer, Novimmune, Sobi, Consultant for: Roche, Novartis, N. Ruperto Grant/research support from: Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer Inc, Roche, Sanofi Aventis, Schwarz Biosciences GmbH, Consultant for: Roche, Speakers bureau: Abbott, AbbVie, Amgen, Astellas, Bristol Myers-Squibb, Boehringer, Celgene, CrescendoBio, EMDSerono, Italfarmaco, Janssen, Medimmune, Novartis, Novo Nordisk, Pfizer, Sanofi, Reumatic.com, Servier, Sinergie, Takeda, H. Brunner: None declared, A. Grom Consultant for: Novartis, Genentech, N. Wulffraat Grant/research support from: European Union (EAHC), M. Henrickson: None declared, R. Jerath: None declared, Y. Kimura Consultant for: Novartis, A. Kadva Employee of: Genentech, C. Keane Employee of: Roche, J. Wang Employee of: Roche, S. Wimalasundera Employee of: Roche, P. Gokani Employee of: Roche, A. Martini Grant/research support from: Roche, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi Aventis, Schwarz Biosciences GmbH, Consultant for: Roche, Speakers bureau: Abbott, AbbVie, Amgen, Astellas, Bristol-Myers Squibb, Boehringer, Celgene, CrescendoBio, EMDSerono, Italfarmaco, Janssen, Medimmune, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Takeda, D. Lovell Grant/research support from: NIH, Consultant for: AstraZeneca, Bristol-Myers Squibb, AbbVie, Pfizer, Roche, Novartis, UBC, Forest Research Institute, Horizon, Johnson & Johnson, Biogen, Takeda, Genentech, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Janssen, Speakers bureau: Genentech, Roche, Novartis