Clinical trial NCT05479448: Predictive Factors for Treatment Response in Patients With Newly-diagnosed Polymyalgia Rheumatica and Giant Cell Arteritis
Official title: Predictive Factors for Treatment Response in Patients With Newly-diagnosed Polymyalgia Rheumatica and Giant Cell Arteritis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Polymyalgia Rheumatica (PMR)
Giant Cell Arteritis (GCA)
Keywords: Large vessel vasculitis (LVV)
Glucocorticoid receptor (GCR)
glucocorticoid (GC)
steroid-response
GCR expression levels
GCR sensitivity/responsiveness
prednisolone
prednisone
Swiss Clinical Quality Management in Rheumatic Diseases (SCQM)
Glucocorticoid resistance
endogenous GC suppression
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
Collaborators: name: Schweizerische Stiftung für die Erforschung der Muskelkrankheiten
name: Novartis
First posted: 2022-07-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients presenting in the University Hospital Basel with newly diagnosed PMR according to the 2012 provisional classification criteria ) and patients with newly diagnosed GCA will be screened for inclusion. Final diagnosis of GCA is made either (i) if temporal artery biopsy is positive, (ii) if patients fulfill the 1989 ACR criteria, or (iii) if they fulfill at least 2/5 ACR criteria in combination with typical vasculitic ultrasound findings or vasculitic findings in other imaging methods.

Brief summary: This prospective study is to explore different predictive factors for response to steroid treatment in patients with PMR and/or GCA. It evaluates the association of endogenous GC suppression (plasma and urinary cortisol and cortisone) to the responsiveness of PMR/GCA to GCs.

Detailed description: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely related inflammatory rheumatic diseases. The first-line treatment of both PMR and GCA are glucocorticoids (GC). In PMR, initial oral prednisone equivalent doses in between 10 and 25 mg/day are given. In contrast, GCA is usually treated with significantly higher steroid doses (starting dose 1 mg/kg body-weight) to prevent vascular complications.

The dose and duration of steroid treatment needed to control disease in patients with PMR and GCA vary and about half of the patients experience relapses, early upon GC dose tapering or after discontinuation of treatment. The reasons for the inter-individual differences in steroid-response are not known. Data from this controlled prospective study will help to identify subjects with GC resistance which would allow to use intensified treatment strategies (higher dose or alternative immune modulatory therapy) to overcome resistance. On the other hand, strong responsiveness to GC would provide a rational for rapid steroid tapering or treatment with lower doses, both resulting in reduced risk for GC related adverse events such as osteoporosis, infections, diabetes and mood disorders. Detailed understanding of the relation of individual GC signaling and GC metabolism with patients' response to steroid treatment will help to define steroid responder profiles. This prospective study is to explore different predictive factors for response to steroid treatment in patients with PMR and/or GCA.

At inclusion and at all follow-up visits, the clinical evaluation will be documented in the SCQM database. All participants with PMR will be treated according to our local treatment protocol: starting dose is 15 mg prednisone/d, tapered by 2.5 mg every second week once symptoms are controlled. After tapering to 10 mg/d, prednisone dose is further reduced by 2.5 mg every month.

All patients with GCA are treated according to published guidelines with prednisone starting at 1mg/kg body-weight followed by reduction to 0 mg at week 26 (GIACTA protocol).

Eligibility criteria: Inclusion Criteria:

* Patients with diagnosis of PMR according to the 2012 provisional classification criteria and GCA according to published criteria
* Consent to participate in the SCQM database
* Treatment according to our standardized regimes

Exclusion Criteria:

* Treatment with Tocilizumab, MTX or other disease modifying medications at inclusion
* History of GCA and PMR in the past
* Inability to give informed consent

Primary outcomes:
measure: Relapse (no/yes) of PMR/ GCA
timeFrame: Within one year after PMR/GCA diagnosis
Secondary outcomes:
measure: Cumulative steroid dose at 1 year after diagnosis
timeFrame: At 1 year after diagnosis
measure: Number of patients with Tocilizumab or other immunosuppressive/ biological treatment started within 1 year after diagnosis.
timeFrame: Within one year after PMR/GCA diagnosis
measure: Number of patients with Methotrexate (MTX) treatment started within 1 year after diagnosis
timeFrame: Within one year after PMR/GCA diagnosis
measure: Prednisone/prednisolone ratio in plasma
timeFrame: Within one year after PMR/GCA diagnosis
measure: Glucocorticoid Toxicity Index (GTI) at 1 year after diagnosis
timeFrame: At 1 year after diagnosis
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Department of Rheumatology University Hospital Basel
Study officials:
affiliation: Department of Rheumatology University Hospital Basel
name: Thomas Daikeler, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: