Safety and Efficacy of Secukinumab for Juvenile Idiopathic Arthritis

Rheumatology Network interviewed Hermine Brunner, MD, MSc, MBA, of the Cincinnati Children's Hospital Medical Center and lead investigator of the JUNIPERA study which reported on the safety and efficacy of secukinumab for patients with juvenile idiopathic arthritis (JIA), presented at the EULAR 2021 Virtual Congress. She also authored the brief report, “New Medications Are Needed for Children With Juvenile Idiopathic Arthritis,” published in Arthritis & Rheumatology,¹ which indicated that despite the availability of biologic disease-modifying antirheumatic drugs (bDMARDs) currently approved for JIA, there is persistent need for additional therapies to control juvenile idiopathic arthritis (JIA) signs and symptoms.

Hermine I. Brunner, MD, MSc, MBA

Rheumatology Network: Can you give me a bit of background on JIA?

Hermine Brunner, MD, MSc, MBA: JIA is the most common rheumatic disease in children. In the currently used diagnostic criteria from the International League of Associations for Rheumatology (ILAR), JIA is divided into 7 distinct categories. Enthesitis-related arthritis (ERA) is the category used to describe the pediatric onset-equivalent of axial spondyloarthritis (SpA) in adults. As per the ILAR criteria, a classification of ERA requires the presence of arthritis plus enthesitis. Another classification of ERA requires arthritis or enthesitis and 2 or more of the following: joint tenderness or inflammatory back pain, HLA-B27 positivity, first-degree relative with disease associated with HLA-B27, acute anterior uveitis, and arthritis in a male individual older than 6 years. Thus, although the criteria for ERA to not require axial arthritis to always be present, many of the same clinical characteristics are considered in order to classify a child as having ERA as what is considered for the classification of non-radiographic SpA.

RN: What first sparked your interest in studying the safety and efficacy of secukinumab (Cosentyx®)?

HB: There are no approved meds in the US for this subtype, thus indicating a large medical need in the treatment of JIA. Approximately 52-65% of all JIA patients have been treated with at least 1 biologic disease-modifying antirheumatic drug (DMARD), and 15-19% have been treated with a biologic that was not approved by the FDA. Even more worrisome, 31-55% of the children demonstrated chronically uncontrolled arthritis, despite the use of these unapproved biologic DMARDS. Secukinumab is a very promising medicine based on results from adult randomized controlled trials (RCTs), considering the known parallels in adult versus pediatric disease.

RN: Can you elaborate on the study design and methods used in your recent study, Evolution in the Understanding of Pediatric-Onset Axial Spondyloarthritis?

HB: Characteristics of JIA patients with pediatric-onset axial SpA were compiled using data from the Childhood Arthritis d Rheumatology Research Alliance (CARRA) registry. This registry included longitudinal data from >5600 children with JIA, including 522 children with ERA and 380 with juvenile PsA. Select characteristics of children for whom sacroiliitis was reported and compared between the first registry visit with clinically active sacroiliitis and the first registry visit without clinically active sacroiliitis. It was identified in 28% of the total group of children with either ERA or juvenile PsA. These children had significantly greater disease burden with higher physician assessment of disease activity, higher parent/patient global assessment of wellbeing, and higher disease activity as measured by the Juvenile Idiopathic Arthritis Disease Activity Score compared with children with ERA or juvenile PsA without sacroiliitis.

RN: What is the clinical significance of this study?

HB: This was the first approved biologic for these JIA categories in the US. It added therapeutic option for Europe where, to the best of my knowledge, tumor-necrosis factors (TNFs) are approved. It also marked improvement of skin involvement with juvenile spondyloarthritis (jPSA) and increases quality of life and stigma of children with chronic arthritis plus psoriasis.

RN: Were there any strengths or limitations of the study that you’d like to discuss?

HB: This randomized study provides high level evidence on efficacy; safety acceptable; low number of injection site reactions and pain; and low frequency of injections after initial loading phase. The study was limited by the lack of specific criteria to determine if the ILAR criteria for ERA and juvenile PsA categories were accurately applied the absence of well-defined criteria for the presence/absence of sacroiliitis, the lack of information on radiologic findings compatible with joint involvement, and the large amount of missing data. However, results indicated that there is a significant proportion of the overall JIA population with non-radiologic SpA that are similar to those of non-radiographic SpA in adults.

RN: Is there anything else you’d like our audience to know?

HB: The study done by Pediatric Rheumatology International Trials Organization (PRINTO) and the Pediatric Rheumatology Collaborative Study Group (PRCSG) network. It marks another success story for the treatment of children with immune-mediated arthritis. Novartis medications added markedly to therapeutic options available.

Reference:

Brunner HI, Schanberg LE, Kimura Y, et al. New Medications Are Needed for Children With Juvenile Idiopathic Arthritis. Arthritis Rheumatol. 2020;72(11):1945-1951. doi:10.1002/art.41390