Long-term treatment with Actemra (tocilizumab) shows sustained safety and effectiveness in children with polyarticular juvenile idiopathic arthritis (pJIA), according to the results of a Phase 3 clinical trial.
The findings, “Long-term, interventional, open-label extension study evaluating the safety of tocilizumab treatment in patients with polyarticular-course juvenile idiopathic arthritis from Poland and Russia who completed the global, international CHERISH trial,” was published in the journal Clinical Rheumatology.
Polyarticular JIA accounts for approximately 30% of all JIA cases. It is characterized by inflammation in five or more joints, usually the hands and feet, and by frequent relapses, long periods of active disease, a higher risk of joint damage, low treatment efficacy, and decreased quality of life.
Actemra — developed by Genentech in the U.S. and available in Europe as RoActemra, marketed by Roche — is an antibody that targets the interleukin (IL)-6 receptor, inhibiting signaling mediated by IL-6, a pro-inflammatory molecule.
The treatment’s effectiveness and safety were observed in the CHERISH Phase 3 trial (NCT01575769) in patients with active pJIA for a minimum of six months and inadequate response to methotrexate (a common arthritis therapy).
Following an initial 16-week open-label period with 8 mg per kg body weight of Actemra every four weeks, 163 patients from Poland and Russia who responded to treatment started a 24-week double-blind phase. Results showed Actemra’s efficacy up to 40 weeks of treatment.
Scientists then aimed to address the intravenous medication’s long-term safety and efficacy, and focused on 41 pJIA patients (33 females, mean age 12, age range 4-19) from Poland (18) and Russia (23) who had completed the CHERISH study. The mean disease duration was 4.8 years.
The open-label extension included patients with at least an ACR (American College of Rheumatology) 70 clinical response to Actemra — meaning a minimum of 70% improvement in three of any six specific variables (physician assessment of disease activity; parent/patient assessment of overall well-being; functional ability; number of joints with active arthritis; number of joints with limited range of motion; and sedimentation rate of red blood cells), and no more than one variable worsening by over 70%.
Enrolled patients also had no adverse events (AEs), serious AEs, or conditions that could cause unacceptable risk of continued treatment.
The extension study was terminated when the medication was approved in both countries for pJIA, so the follow-up period varied from 27 to 89 weeks. Total treatment time – including all phases of CHERISH – ranged from 131 to 193 weeks, making this “the longest published observation of patients with pJIA treated with [Actemra],” the researchers noted.
While safety was evaluated throughout the entire extension duration and a later follow-up visit, efficacy was assessed every four weeks during the first 24 weeks (total time 128 weeks) when all patients remained in the study.
Results showed that methotrexate was the most commonly used concomitant medication, in 29 of 34 patients with available data.
A total of 23 patients experienced 84 AEs during the study. Ten patients had mild (24.4%), while 12 had moderate (29.3%) AEs. Pharyngitis (14.6%) and upper respiratory tract infections (12.2%) were the most common AEs.
Twelve patients had AEs considered remotely, probably, or possibly related to the medication. Those possibly related did not require a change of dosing.
Three severe AEs (7.3%) were observed due to neutropenia, or low neutrophil count, mild proteinuria (excessive protein amounts in urine), and multiple injuries of moderate severity. Of these, only the neutropenia case was thought to be probably related to Actemra, and the patient was withdrawn from the study.
Eight other patients also needed dose modifications: five due to respiratory tract infections, two due to dermatitis, and one because of hyperbilirubinemia, or too much bilirubin in the blood.
Overall, the rate of AEs during the follow-up extension period was lower than in the CHERISH core study, the investigators observed.
As for the drug’s effectiveness, 40 of 41 patients continued to achieve ACR70 up to week 24. The remaining patient decreased to ACR50, which has the same criteria as ACR70, but with a 50% threshold.
Also, comparing baseline to week 24, the number of patients with inactive disease increased from 26 to 31, while that of patients with clinical remission increased from 18 to 20.
“Taken together, the continued efficacy response and the consistent safety profile support the use of [Actemra] in pJIA,” the team wrote.
Four of the study’s authors received funding and/or speaker’s fees from pharmaceutical companies, including Roche. One author was an employee of Roche Polska.