Tocilizumab Impresses in Polyarticular Juvenile Arthritis

Alice Goodman

June 19, 2013

MADRID, Spain — Children with polyarticular juvenile idiopathic arthritis treated with tocilizumab (Actemra, Genentech) achieved high response rates with sustained improvement in the phase 3 CHERISH trial.

The results prompted the US Food and Drug Administration to approve tocilizumab for this indication. The drug is already approved for systemic juvenile idiopathic arthritis and for adults with moderate to severe rheumatoid arthritis.

"Juvenile idiopathic arthritis has no known cause and can lead to joint damage and permanent disability. These data show that tocilizumab rapidly improves signs and symptoms of polyarticular juvenile arthritis, with meaningful responses achieved in a large proportion of patients at week 40," said lead investigator Fabrizio De Benedetti, MD, from Ospedale Pediatrico Bambino Gesù in Rome, Italy.

"The data suggest that tocilizumab is going to be a novel biologic part of the therapeutic armamentarium for polyarticular juvenile arthritis," he said here at the European League Against Rheumatism Congress 2013.

Tocilizumab is a humanized monoclonal antibody that blocks interleukin-6 receptors, preventing proinflammatory activity.

CHERISH is a 3-year international trial conducted at 58 centers in 15 countries and overseen by the Paediatric Rheumatology Collaborative Study Group and the Paediatric Rheumatology International Trials Organization.

The study involved 188 children with active polyarticular juvenile arthritis for at least 6 months and a failed response to methotrexate. Patients could remain on background methotrexate or nonsteroidal anti-inflammatory drugs, or both, if they were taking these drugs at study entry.

In part 1 of CHERISH, patients received tocilizumab every 4 weeks for 16 weeks. The 166 patients who achieved an American College of Rheumatology response of 30% (ACR30) moved on to part 2 of the study, in which they were randomized to tocilizumab or placebo for 24 weeks.

Dr. De Benedetti presented the part 2 results.

At baseline, median age in the tocilizumab group was 11 years, median disease duration was 4 years, and the number of active joints was 20. In that group, 80% of patients were taking methotrexate and 32% had previously been treated with a biologic.

There were fewer disease flares at week 40, the primary outcome, in the tocilizumab group than in the placebo group (26% vs 48%; P = .0024).

Table. Response Rates in Tocilizumab-Treated Patients

Response Percent
ACR30 74
ACR50 53
ACR70 65
ACR90 45


In the tocilizumab group, more patients taking methotrexate achieved an ACR70 response (67% vs 53%) and an ACR90 response (47% vs 33%).

In contrast, fewer patients in the tocilizumab group who received previous biologic therapy achieved an ACR70 response (48% vs 72%) and an ACR90 response (19% vs 58%)

Tocilizumab has a long track record, and no new safety signals emerged in the CHERISH trial, Dr. De Benedetti reported.

In the tocilizumab-treated children, the rate of serious adverse events was 12.5 per 100 patient-years, and the rate of serious infections was 4.9 per 100 patient-years. This is consistent with the known safety profile of tocilizumab, he noted.

Yukiko Kimura, MD, a CHERISH trial investigator who was not involved with this part of the study, told Medscape Medical News that even though tocilizumab has already been approved for use in systemic juvenile arthritis, the approval for polyarticular juvenile arthritis is "an important milestone."

"It allows us to add another effective therapy to our armamentarium for polyarticular juvenile arthritis," she said. "We now have many effective treatment choices for various inflammatory diseases, which has dramatically improved the health and outcomes of children with juvenile arthritis." Dr. Kimura is chief of pediatric rheumatology at the Joseph M. Sanzari Children's Hospital, Hackensack University, in New Jersey.

"Having choices is important because each patient responds differently to a given treatment," added Dr. Kimura. "The next step will be to understand how each of these effective new treatments compares with the other in terms of overall effectiveness and safety, and ultimately to know ahead of time which medication will be the most effective for each patient."

Dr. De Benedetti reports receiving grant and research support from Abbott, Pfizer, BMS, Roche, NovImmune, Novartis, and SOBI. Dr. Kimura has disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2013. Abstract OP0060. Presented June 13, 2013.


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