chronic inflammation of the joints psoriatic arthritis Rheumatoid arthritis
Conditions
Interventions
Reference treatment
All patients are using the conventional dose of tofacitinib which is
tofacitinib 5mg BID orally.
Intervention treatment
For 2-6 weeks, patients will switch to tofacitinib 5mg or
Sponsors
Radboud Universitair Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Rheumatoid arthritis (either 2010 ACR RA and/or 1987 RA criteria and/or clinical diagnosis of the treating rheumatologist, fulfilled at any time point between start of the disease and inclusion) or Psoriatic arthritis (either Classification Criteria for Psoriatic Arthritis (CASPAR) and/or diagnosed with peripheral SpA of the psoriatic arthritis subtype by a rheumatologist) * Patients using tofacitinib for * 2 weeks in the standard dose of 5mg BID. * Patient informed consent, *18 years old and mentally competent * Ability to measure the outcome of the study in this patient (e.g. patient availability; willing and being able to undergo repeated serum samples) * Ability to read and communicate well in Dutch
Exclusion criteria
Exclusion criteria: * Concomitant use of inducers or potent inhibitors of CYP3A4 or moderate inhibitors of CYP3A4 and potent inhibitors of CYP2C19, or medication sensitive to changes in metabolism as a result of cobicistat co-treatment, as assessed with the KNMP *G-standaard* unless an alternative is listed in Table 1. * Known contra-indications for treatment with cobicistat in line with the summary of product characteristics
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To investigate the bioequivalence of tofacitinib 5mg and cobicistat 150 mg QD (intervention) compared to tofacitinib 5mg BID alone (control) with regard to the relevant steady state pharmacokinetic parameters (average concentration at steady state (Cavg,ss )/Area Under the Curve (AUC0-24), as defined by a 90% confidence interval of the geometric mean ratio falling entirely between 75% and 125%. | — |
Secondary
| Measure | Time frame |
|---|---|
| * To construct a mechanistic population pharmacokinetic model describing the quantitative effect of cobicistat on tofacitinib pharmacokinetics; * To describe the relevant pharmacokinetic parameters (Cavg,ss, AUC0-24, Cmax,ss, tmax,ss, Ctrough and t1/2) after administration of tofacitinib 5mg and cobicistat 150 mg QD compared to tofacitinib 5mg BID alone; * To evaluate the safety and tolerability of tofacitinib 5mg and cobicistat 150 mg QD compared to tofacitinib 5mg BID alone; * To provide a suitable dosing scheme of tofacitinib and cobicistat for a future clinical non-inferiority study, based on the developed pharmacokinetic model, in case tofacitinib 5mg and cobicistat 150 mg QD is not equivalent to tofacitinib 5mg BID alone in this study; * To evaluate the efficacy of both regimes by DAS28-CRP; * To establish which regimen is preferred by patients based on medication QD or BID. | — |
Countries
Netherlands
Outcome results
None listed