Madrid, Spain, 12 June 2013: A new study presented today at EULAR 2013, the Annual Congress of the European League Against Rheumatism shows that tocilizumab is efficacious and leads to a sustained clinically meaningful improvement in children with polyarticular Juvenile Idiopathic Arthritis (pcJIA).
Tocilizumab is a humanized recombinant antibody, which blocks the receptors where interleukin-6 (IL-6) attaches to the surface of cells. When IL-6 is unable to attach to these cells, they are prevented from driving inflammation. Elevated serum and joint fluid IL-6 levels have been shown to be associated with disease activity in patients with pcJIA.1
"JIA is a chronic arthritis occurring in 1 in every 1,000 children. With no known cause, it can lead to joint damage and permanent disability. These data show that tocilizumab rapidly improves signs and symptoms of pcJIA, with meaningful clinical responses maintained in a large proportion of patients at week 40," said lead author Dr. Fabrizio De Benedetti of the IRCCS Ospedale Pediatrico Bambino Gesu, Rome.
Speaking on behalf of the Paediatric Rheumatology International Trials Organisation (PRINTO) and Pediatric Rheumatology Collaborative Study Group (PRCSG), who had overseen this study, Dr. De Benedetti concluded that "these data suggest that tocilizumab is going to be a novel biologic part of the therapeutic armamentarium for pcJIA."
CHERISH is a two-year, 3-part trial being conducted at 58 centres across 15 countries. Patients aged 2-17 years were included in the study if they had active pcJIA for at least 6 months and had failed to respond to methotrexate (a cornerstone of therapy worldwide for this condition).
Part 1 of the study was a 16-week open-label phase in which 188 patients received tocilizumab every four weeks. The 166 patients who achieved at least a 30% improvement in symptoms and signs of pcJIA (an JIA ACR30* response) went on to part 2, which was a 24-week study in which patients were randomised to continue on the same dose of tocilizumab or to receive placebo. Part 3 is an ongoing open-label study.
For the primary end point of ACR30 flare, fewer patients in the tocilizumab group than in the placebo group experienced a flare by week 40 (25.6% vs. 48.1%) and JIA ACR30/50/70* responses were significantly higher with tocilizumab than placebo, with as many as 65% of the children attaining an ACR70 response.
Dosing of tocilizumab was based on the patient's body weight (BW): with a BW ≥30 kg, the dose was 8 mg/kg [n=119]; with a BW <30 kg, patients were randomly assigned to 8 mg/kg [n=34] or 10 mg/kg [n=35].
"The degree of improvement at week 16 was lower for each of the endpoints for patients under 30 kg on 8 mg/kg tocilizumab than in the other two treatment groups. The data therefore support the efficacy of tocilizumab in pcJIA using a monthly regimen at doses of 8 mg/kg if BW 30 kg or more, and 10 mg/kg if BW under 30 kg," Dr. De Benedetti added.
Patients were also taking background medications, such as methotrexate and oral corticosteroids (79% and 46% respectively).
Tocilizumab's safety profile was consistent with that found in other tocilizumab-treated patients.2 At the safety data cut, 184 patient years of follow-up had occurred in the 188 patients enrolled. Infection was the most common adverse event (164/100 patient years) and serious adverse event (4.9/100 patient years). Liver enzyme (ALT/AST) elevations ≥3× upper limit of normal occurred in 3.7 % / <1% of patients, neutropenia (<1000 cells/mm3) in 3.7% of patients, thrombocytopenia (<50,000 cells/mm3) in 1.1% of patients. An elevation of LDL-cholesterol ≥110 mg/dl was reported in 11.4% of patients who received tocilizumab.
*JIA ACR30 response is defined as an improvement of at least 30% from the baseline assessments in any three of six core outcome variables, with no more than one of the remaining variables deteriorating by more than 30%. JIA ACR50 refers to a 50% improvement and JIA ACR70 refers to a 70% improvement, with no more than one of the remaining variables deteriorating by more than 50% and 70% respectively. The JIA core outcome variables are: active joint count, limitation of motion joint count, physician global assessment, patient/parent global assessment, Childhood Health Assessment Questionnaire (CHAQ), and acute-phase reactant level (either ESR or CRP).
1.De Benedetti F et al., Efficacy and safety of tocilizumab in patients with polyarticular juvenile idiopathic arthritis: data from a phase 3 trial [abstract]. EULAR Annual European Congress of Rheumatology; 12-15 June 2013; Madrid, Spain. Abstract nr. OP0060.
2.De Benedetti F, Robbioni P, Massa M, et al. Serum interleukin-6 levels and joint involvement in polyarticular and pauciarticular juvenile chronic arthritis. Clin Exp Rheumatol. 1992; 10 (5): 493-8
3.De Benedetti F, Brunner HI, Ruperto N, et al, Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367:2385-95.
NOTES TO EDITORS:
For further information on this study, or to request an interview with the study lead, please do not hesitate to contact the EULAR congress Press Office in room A10:14 of the Congress Centre during EULAR 2013 or on:
EULAR Press Office
Onsite tel: +44 (0) 20 7331 5364 / 5380 / 5318 / 2305