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Research project

ChronIA trial

Status: Ongoing project

Open-label, randomized controlled trial to compare the clinical effectiveness of tofacitinib extended release (XR) chronotherapy in rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients.

What we do

About our project

The ChronIA (Chronotherapy in Inflammatory Arthritis) trial was set up to study if timing of treatment, known as chronotherapy, improves the efficacy of tofacitinib XR  in inflammatory arthritis (IA). The primary outcome is the difference in self-reported disease activity, measured with the Routine Assessment of Patient Index Data 3 (RAPID-3), between morning and evening dosing of tofacitinib XR after 3 months of treatment. 

Our research focus

Circadian rhythms are vital for a lot of physiological processes and can be observed in various daily activities (i.e. eating and sleeping). In line with this, various IA symptoms show a distinctive diurnal pattern, including pain and joint stiffness. Moreover, the daily variation of pro-inflammatory cytokines are altered in IA patients due to a change in the expression of circadian clock genes, which leads to a desynchronization of the circadian rhythm. This desynchronization of the circadian rhythm may lead to dysbiosis, but one can also reason vice versa. Biologicals modulate the expression of circadian clock genes in a positive manner, which might also lead to a balanced microbiota, or eubiosis, that reliefs symptoms. 

Although aforementioned reasoning makes it plausible that the timing of treatment in inflammatory arthritis might improve the efficacy of the given drug, there are only a handful of trials that have investigated this concept. In the past chronotherapy using NSAIDs, glucocorticoids and methotrexate were investigated, which showed a significant improvement in symptoms, including functional ability, morning stiffness and disease activity, but also a reduction in dosage without loss of efficacy. However, studies looking into chronotherapy using biologicals and/or JAK inhibitors in inflammatory arthritis patients are non-existing. 

Lastly, we want to emphasize that most clinical research in inflammatory arthritis on circadian rhythms and chronotherapy is exclusively done in rheumatoid arthritis.  
Therefore, the aim of this project is to compare the effectiveness of tofacitinib XR chronotherapy, morning versus evening dosing, in IA, rheumatoid arthritis and psoriatic arthritis, patients. 
Furthermore, we aim to evaluate if sleep quality, morning stiffness severity and the patient-relevant outcome (PRO) domains pain, fatigue, activity limitation, quality of life and worker productivity differ between morning and evening dosing of tofacitinib XR. Lastly, we will investigate if the expression of circadian clock genes change over time and correlate with treatment response, and whether treatment with tofacitinib XR leads to restoration of eubiosis. 
 

Our team

Contact us: chronia@erasmusmc.nl

 

Pascal de Jong, MD PhD

Selinde Snoeck Henkemans, MD

Anke Nijs

Ron Buijs