Evaluation of Intra-Articular Triamcinolone Hexacetonide Injections in Juvenile Idiopathic Arthritis Patients Initiating Tumor Necrosis Factor Inhibitor Therapy

The primary objective of this study is to evaluate whether **intra-articular glucocorticoid injections** in joints with active arthritis enhance the proportion of patients with **Juvenile Idiopathic Arthritis** (JIA) achieving sustained inactive disease when initiating treatment with Tumour Necrosis Factor (TNF) inhibitors, compared to a control group not receiving joint injections. This is clinically relevant as achieving sustained inactive disease is a critical goal in the management of JIA, potentially reducing long-term joint damage and improving quality of life.

Secondary objectives include comparing the efficacy of the two treatment regimens over a follow-up period of up to 24 weeks. This comparison will provide insights into the short-term benefits and potential differences in treatment outcomes, aiding in the optimization of therapeutic strategies for JIA.

The clinical trial focuses on participants diagnosed with **Juvenile Idiopathic Arthritis** (JIA), aiming to evaluate the efficacy of intra-articular glucocorticoid injections in conjunction with Tumour Necrosis Factor (TNF) inhibitor treatment. The study population includes both male and female subjects, aged between 1 and 18 years, who meet the International League of Associations for Rheumatology (ILAR) classification criteria for non-systemic JIA. Participants are required to have a clinical indication for initiating TNFi treatment, as agreed upon by at least two physicians, and must be either TNFi-naïve or have previously used one TNFi, provided it was discontinued at least three months prior to study inclusion without any prior TNFi treatment failure. The trial involves a vulnerable population, and participants must have a Juvenile Disease Activity Score (JADAS) greater than 1 at baseline, with at least one joint exhibiting active arthritis where joint injection is considered. Written consent is mandatory, with participants aged 16 and above providing their own consent, while guardians provide consent for those under 16, and both participants and guardians provide consent for those aged 16 to 18. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the effectiveness of intra-articular glucocorticoid injections in patients with **Juvenile Idiopathic Arthritis** (JIA) who are initiating treatment with Tumour Necrosis Factor inhibitors (TNFi). This is a randomized, multicentre, blinded-assessor trial, with a control group not receiving joint injections. The primary objective is to determine if these injections increase the proportion of patients achieving sustained, inactive disease compared to the control group. The trial commenced on December 1, 2020, and is expected to conclude by February 6, 2025, with recruitment having started on October 1, 2020, and ending on March 14, 2024.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (1-18 years), fulfillment of the International League of Associations for Rheumatology classification criteria for non-systemic JIA, and clinical indication for starting TNFi treatment. Follow-up visits will be scheduled to monitor the participants' response to treatment, with primary endpoints assessed between weeks 24 and 36. The end-of-study visit will evaluate the overall outcomes and any adverse events. The expected length of participant involvement is approximately 36 weeks, with conditions for early termination including non-compliance with the study protocol or withdrawal of consent.

The trial employs **triamcinolone hexacetonide** as the active substance, administered as a suspension for injection. The maximum daily dose is 3.5 mg/kg, with a total treatment period of one month. Participants are required to provide written consent, and the study protocol mandates compliance with all procedural requirements. The trial's primary endpoint is the proportion of participants with sustained, inactive disease without glucocorticoid use from week 24 to 36, while secondary endpoints include a 30% improvement in the paediatric American College of Rheumatology criteria at week 24. The trial is categorized as a Phase IV clinical trial, focusing on the long-term effects and safety of the treatment in a real-world setting.

The clinical trial involves the use of **Lederspan**, a pharmaceutical product formulated as a **suspension for injection**. The active substance in Lederspan is **triamcinolone hexacetonide**, a chemical compound classified under the ATC code H02AB08, which corresponds to **triamcinolone**. The medication is administered via **injection** and is intended for use in patients with **Juvenile Idiopathic Arthritis** (JIA). The maximum daily dose is 3.5 mg/kg, with the same amount being the maximum total dose allowed. The treatment period is limited to a maximum of one day. The product is not a pediatric formulation and is not classified as an orphan drug. The manufacturer of Lederspan is Viatris APS, and the product is authorized for use in Denmark.

In addition to the experimental treatment, the study includes a control group that does not receive joint injections. This group serves as a comparator to evaluate the effectiveness of the intra-articular glucocorticoid injections in conjunction with the initiation of Tumour Necrosis Factor (TNF) inhibitor treatment. The trial aims to determine if the combination of these treatments increases the proportion of JIA patients achieving sustained, inactive disease compared to those who do not receive the joint injections. Compliance with the dosing schedule and administration is monitored throughout the trial to ensure adherence to the protocol.

Efficacy in the clinical trial titled "Strategies towards personalised treatment in Juvenile Idiopathic Arthritis (JIA)" will be assessed using specific primary and secondary endpoints. The primary endpoint is the proportion of participants achieving sustained, inactive disease according to the Wallace 2011 criteria, without the use of intra-articular (i.a.) or oral (p.o.) glucocorticoids from week 24 to 36. This endpoint is designed to evaluate the long-term effectiveness of the treatment strategy in maintaining disease inactivity.

The secondary endpoint involves a 30% improvement in the paediatric American College of Rheumatology criteria (ACR Pedi 30 improvement) at week 24. This measure will provide additional insight into the short-term efficacy of the treatment in improving disease symptoms. The trial will utilize these endpoints to determine the effectiveness of intra-articular glucocorticoid injections in conjunction with Tumour Necrosis Factor (TNF) inhibitor treatment in JIA patients.