Evaluation of Golimumab Versus Conventional Synthetic DMARDs in Inducing Remission in Peripheral Spondyloarthritis: A Randomized Controlled Trial

The primary objective of this study is to compare a standard step-up approach using conventional synthetic **Disease-Modifying Anti-Rheumatic Drugs** (csDMARDs), such as methotrexate and/or sulphasalazine, with an early remission-induction treatment strategy that immediately introduces biological DMARDs (bDMARDs) as the first step in the treatment algorithm. In this group, the **Tumor Necrosis Factor** inhibitor (TNFi) golimumab will be utilized. This comparison is clinically relevant as it aims to determine the efficacy of early intervention with bDMARDs in achieving drug-free remission in patients with **Peripheral Spondyloarthritis**, potentially altering the standard treatment paradigm.

Secondary objectives include defining the window of opportunity within which temporary treatment with bDMARDs might be more effective. This will be achieved by analyzing patients according to symptom duration, either as a continuous variable or by comparing patients with shorter symptom duration (<3 months) versus those with more longstanding disease (between 3-12 months of symptom duration).

The clinical trial focuses on individuals diagnosed with **peripheral spondyloarthritis**, a condition characterized by inflammation primarily affecting the joints and entheses. The study population includes both male and female participants aged between 18 and 65 years. Participants are required to have been diagnosed by a rheumatologist and must meet the ASAS classification criteria for peripheral spondyloarthritis. The trial does not include vulnerable populations. Participants must exhibit active disease at screening, as defined by a Patient Global Assessment of Disease Activity Numerical Rating Scale (NRS) of 4 or higher, and a Patient Global Assessment of Pain NRS of 4 or higher. The onset of peripheral SpA symptoms must have occurred within 12 months prior to the screening visit. The sponsor has not provided information regarding the total number of participants in the trial. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of two treatment strategies for **peripheral spondyloarthritis**. The study employs a randomized, double-blind, controlled design to ensure unbiased results. Participants will be randomly assigned to either a standard step-up approach using conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) or an early remission-induction strategy with biological DMARDs, specifically the Tumor Necrosis Factor inhibitor (TNFi) **golimumab**. The trial is expected to run until December 31, 2028, with recruitment having started on August 21, 2020.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis, and disease activity. Follow-up visits will occur at regular intervals to monitor treatment efficacy and safety, with assessments including clinical remission rates, joint counts, and patient-reported outcomes. The end-of-study visit will conclude the participant's involvement, summarizing the overall treatment effects and any adverse events experienced.

The expected duration of participant involvement is up to 36 weeks, with conditions for early termination including significant adverse events or withdrawal of consent. The primary endpoint is the proportion of patients achieving clinical remission, while secondary endpoints include sustained remission rates, improvement in clinical assessments, and changes in inflammatory markers. The trial will also compare the occurrence of adverse events between the two treatment strategies.

The clinical trial involves the administration of **Simponi** (golimumab), a **Tumor Necrosis Factor inhibitor** (TNFi), which is utilized in the "TNFi Induction" strategy. Simponi is provided as a 50 mg solution for injection, available in both pre-filled pens and pre-filled syringes. The pharmaceutical form is a solution for injection, and the route of administration is **subcutaneous**. The maximum daily dose is 0.02 ml, with a total maximum dose of 4.5 ml over a treatment period of up to 36 months. The product is manufactured by Janssen Biologics B.V. and is classified under the ATC code L04AB06. The solution is a recombinant, immunological product, and encapsulation is used for blinding purposes in some formulations.

Another treatment used in the trial is **Ledertrexate** (methotrexate disodium), which is part of the "csDMARD Step-Up" strategy. Ledertrexate is available as 2.5 mg tablets, with a maximum daily dose of 2.85 mg and a total maximum dose of 720 mg over a 36-month period. The route of administration is **oral use**. The tablets are manufactured by Pfizer S.A. and are classified under the ATC codes L01BA01 and L04AX03. Encapsulation is also employed for blinding purposes in this formulation.

The trial includes the use of a **placebo** for comparative purposes. The placebo is designed to match the active treatments in appearance but does not contain the active substance. It is manufactured by the same manufacturer as the Golimumab Blinded IMP and is not sterile. The placebo is used to ensure the blinding of participants and investigators to the treatment assignments.

The clinical trial aims to assess the efficacy of two treatment strategies for patients with peripheral **Spondyloarthritis** (pSpA). The primary endpoint for evaluating efficacy is the proportion of patients achieving clinical remission. Secondary endpoints include the achievement of sustained clinical remission at week 24 and week 36 for patients remaining on blinded study medication. Additionally, improvements from baseline to weeks 12 and 24 will be measured in individual clinical assessments such as the 78-Tender Joint Count, 76-Swollen Joint Count, Dactylitis Count, and SPARCC Enthesitis Score, as well as composite scores like the Axial Spondyloarthritis Disease Activity Score (ASDAS).

Patient-reported outcomes will also be evaluated, including the Patient Global Assessment of Disease Activity and Pain, BASDAI, BASFI, and ASAS Health Index. Inflammatory parameters such as ESR and CRP will be monitored for changes from baseline to weeks 12 and 24. The trial will also compare changes in concomitant NSAID intake and the use of "escape" intra-articular glucocorticoid injections between baseline and week 24. The occurrence of adverse events and adverse events of specific interest will be descriptively analyzed between the two treatment strategies from baseline to week 24, and week 36 for patients on blinded study medication. The percentage of patients achieving sustained clinical remission with open-label golimumab treatment after failure of the initial randomized, blinded treatment strategy will be explored, with a focus on symptom duration.