Chronotherapy in Rheumatoid and Psoriatic Arthritis: A Randomized Controlled Trial of Tofacitinib Extended-Release Morning vs. Evening Dosing

The primary objective of the Chronotherapy in Inflammatory Arthritis (ChronIA) trial is to evaluate the difference in **self-reported disease activity** between morning and evening dosing of tofacitinib extended-release (XR) in patients with rheumatoid arthritis or psoriatic arthritis. This is measured using the Routine Assessment of Patient Index Data 3 (RAPID-3) after 3 months of treatment. The clinical relevance of this objective lies in optimizing dosing schedules to potentially enhance therapeutic outcomes and improve patient quality of life.

Secondary objectives include assessing various patient-reported outcomes and biological markers:

• **Disease activity** (self-reported states)
• **Morning stiffness**
• **General health**
• **Fatigue**
• **Pain**
• **Sleep**
• **Functional ability**
• **Quality of life**
• **Worker productivity**
• **Treatment satisfaction**
• **Compliance**
• Changes in expression of **circadian clock genes**
• Changes in **microbiota composition**

The clinical trial involves participants diagnosed with **rheumatoid arthritis** or psoriatic arthritis, as defined by the 2010 ACR/EULAR criteria or CASPAR criteria, respectively. The study population includes both male and female subjects aged 18 years and older. Participants are required to have active disease, characterized by a DAS greater than 2.4 or a DAPSA greater than 14. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The selection criteria ensure that participants have a confirmed diagnosis and active disease status, which are critical for evaluating the primary outcome of the study.

The clinical trial is designed to evaluate the effectiveness of **tofacitinib** extended-release tablets in patients with **rheumatoid arthritis** or **psoriatic arthritis**. This study employs a randomized, controlled trial design to compare the outcomes of morning versus evening dosing of the medication. The trial is double-blind to ensure unbiased results, with neither participants nor investigators aware of the dosing schedule assigned to each participant. The trial is expected to span approximately four years, with an estimated end date of October 30, 2026.

Participants will undergo a series of study visits, beginning with an inclusion visit to screen for eligibility based on criteria such as age (≥18 years) and active disease status (DAS>2.4 or DAPSA>14). Following successful screening, participants will be randomized into one of the dosing groups. The primary endpoint is the difference in self-reported disease activity, measured using the Routine Assessment of Patient Index Data 3 (RAPID-3), after three months of treatment. Secondary endpoints include assessments of morning stiffness, general health, fatigue, pain, sleep, functional ability, quality of life, worker productivity, treatment satisfaction, and compliance. Additionally, the study will explore changes in circadian clock gene expression and microbiota composition over time and their correlation with treatment response.

Participants are expected to be involved in the study for a maximum of six months, corresponding to the maximum treatment period with the study medication. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or adverse events that necessitate discontinuation of the medication. The study will conclude with an end-of-study visit to assess final outcomes and gather data for analysis. The trial's findings aim to provide insights into the optimal timing of **tofacitinib** administration to enhance therapeutic efficacy in managing **rheumatoid arthritis** and **psoriatic arthritis**.

The clinical trial involves the administration of **XELJANZ** 11 mg **prolonged-release tablets**, which contain the active substance **tofacitinib**. This medication is formulated as a prolonged-release tablet, designed to release the active ingredient over an extended period. The tablets are administered orally, with a maximum daily dose of 11 mg. The treatment period for this trial is set at a maximum of six months. The primary objective of the trial is to compare the effectiveness of morning versus evening dosing of tofacitinib extended-release in patients with inflammatory arthritis, with the main outcome being the difference in self-reported disease activity after three months of treatment.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial focuses solely on the administration of the experimental medication, XELJANZ, to evaluate its efficacy in the context of chronotherapy for inflammatory arthritis. Participant compliance with the dosing schedule is monitored to ensure adherence to the prescribed regimen, which is critical for assessing the treatment's effectiveness accurately.

Efficacy in the clinical trial titled "Chronotherapy in Inflammatory Arthritis (ChronIA trial)" will be assessed primarily through the measurement of self-reported disease activity using the **Routine Assessment of Patient Index Data 3 (RAPID-3)**. This primary endpoint evaluates the difference in disease activity between morning and evening dosing of tofacitinib extended-release (XR) after 3 months of treatment. Secondary endpoints include various self-reported measures such as disease activity states, morning stiffness, general health, fatigue, pain, sleep, functional ability, quality of life, worker productivity, treatment satisfaction, and compliance. Additionally, the trial will explore whether changes in the expression of circadian clock genes and microbiota composition correlate with treatment response over time.