A4: Efficacy and Safety of Tocilizumab in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: 2-Year Data From CHERISH
Authors: Hermine Brunner, Nicolino Ruperto, Zbigniew Zuber, Rubén J. Cuttica, Ricardo Xavier, Inmaculada Calvo, Nadina Rubio, Ekaterina Alekseeva, Vyacheslav Chasnyk, Jose Chavez, Gerd Horneff, Violetta Opoka-Winiarska, Pierre Quartier, Alberto Spindler, Caroline Keane, Kamal N. Bharucha, Jianmei Wang, Daniel J. Lovell, Alberto Martini, Fabrizio De Benedetti
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

The efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, were previously demonstrated at week 40 of CHERISH, a phase 3 trial in patients with polyarticular-course juvenile idiopathic arthritis (pcJIA) ([1]). Here we report the efficacy and safety of TCZ over 104 weeks of treatment in patients with pcJIA.



Methods:

Patients 2 to 17 years old with ≥6 months' active pcJIA who failed methotrexate received open-label TCZ (weight ≥30 kg, 8 mg/kg [n = 119]; weight ≥30 kg, randomly assigned [1:1] to 8 [n = 34] or 10 [n = 35] mg/kg) every 4 weeks for 16 weeks. Patients with ≥JIA American College of Rheumatology (ACR) 30 response at week 16 entered a 24-week, double-blind withdrawal period and were randomly assigned (1:1) to placebo or continuation with TCZ. Patients with JIA ACR30 flare or who completed the withdrawal period entered an open-label extension through week 104.



Results:

One hundred eighty-eight patients entered the lead-in period, 166 entered the withdrawal period, 160 entered the open-label extension period, and 155 completed 104 weeks. In patients who received continuous TCZ throughout the study (n = 82), JIA ACR responses, improvement in JIA ACR core components, and proportions of patients with inactive disease or remission (1) were maintained through week 104. JADAS-71 scores were maintained through week 104 (Figure); 73% of patients had JADAS-71 <3.8 (minimal disease activity cutoff), 56% had JADAS-71 <1 (inactive disease cutoff). The safety population comprised 188 patients with 307 patient-years (PY). Rates/100 PY of adverse events (AEs) and serious AEs (SAEs) were 406.5 and 11.1, respectively; infections were the most common AE (151.4) and SAE (5.2). ALT and AST elevations ≥3× upper limit of normal occurred in 6.4% and 2.7% of patients, respectively. Grade 3 lowest neutrophil count and grade 2/3/4 thrombocytopenia occurred in 5.9% and 1.6% of patients, respectively. LDL cholesterol ≥110 mg/dL occurred in 16.2% of patients. 


Table 1. Efficacy End Points and Percentage Change From Baseline in JIA ACR Componentsa (continuous TCZ, n = 82)	 	Baseline	Week 40	Change from baseline to week 40, %	Week 104	Change from baseline to week 104, %




Data are mean ± SD, unless stated otherwise.




Patients who withdrew because of nonsafety reasons are nonresponders. Patients who withdrew because of safety are included using last observation carried forward.


a

Patients who withdrew are excluded.


b

Parent-rated.


c

No active joints, no active uveitis, ESR <20 mm/h, and physician global assessment VAS ≤10.


d

Met criteria for inactive disease at each visit for 6 preceding months.




	
JIA ACR70 responders,a n (%)	–	65 (79.3)	–	71 (86.6)	–	
JIA ACR90 responders,a n (%)	–	65 (79.3)	–	71 (86.6)	–	
Active joints (0–71)	19.7 ± 14.0	4.7 ± 9.1	−82.4 ± 24.9	3.3 ± 9.1	−87.7 ± 27.1	
Joints with limitation of movement (0–67)	16.5 ± 13.8	5.6 ± 10.1	−73.5 ± 30.7	3.6 ± 7.3	−81.3 ± 31.7	
Patient globalc (VAS 0–100 mm)	45.5 ± 23.1	12.2 ± 19.0	−62.5 ± 76.3	9.1 ± 18.4	−75.4 ± 43.8	
Patient globalb (VAS 0–100 mm)	45.5 ± 23.1	12.2 ± 19.0	−62.5 ± 76.3	9.1 ± 18.4	−75.4 ± 43.8	
Physician global (VAS 0–100 mm)	57.8 ± 20.3	8.8 ± 10.9	−85.3 ± 16.8	5.0 ± 10.5	−89.7 ± 23.7	
CHAQ-DI (0–3)	1.2 ± 0.7	0.4 ± 0.5	−66.0 ± 44.7	0.2 ± 0.4	−76.7 ± 34.7	
ESR (mm/h)	31.7 ± 22.9	5.4 ± 6.3	−76.5 ± 22.0	5.1 ± 5.6	−76.2 ± 27.3	
Inactive disease,c n (%)	–	33 (40.2)	–	52 (63.4)	–	
Remission,d n (%)	–	5 (6.1)	–	31 (37.8)	–	
Minimal disease activity (JADAS-71 <3.8), n (%)	0 (0)	49 (59.8)	–	60 (73.2)	–	
Inactive disease (JADAS-71 <1), n (%)	0 (0)	24 (29.3)	–	48 (58.5)	–	



Conclusion:

The efficacy of TCZ was maintained through 2 years of treatment in patients with pcJIA, with no change in safety profile from that reported previously ([1]).