Predictive Factors for Treatment Response in Patients With Newly-diagnosed Polymyalgia Rheumatica and Giant Cell Arteritis

Sponsor

University Hospital, Basel, Switzerland (Other)

Overall Status

Recruiting

CT.gov ID

NCT05479448

Collaborator

Schweizerische Stiftung für die Erforschung der Muskelkrankheiten (Other), Novartis (Industry)

Enrollment

Location

24.9

Anticipated Duration (Months)

1.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Polymyalgia Rheumatica (PMR) Giant Cell Arteritis (GCA)	Other: Data collection for cellular analyses (Immune subset composition, GCR expression, in vitro steroid responsiveness) Other: Data collection for exploratory analyses of endogenous steroid hormones Other: Data collection for correlation between clinical defined and lab defined GC responsivness Other: Data collection for Prednisone metabolism

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).

Study Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Predictive Factors for Treatment Response in Patients With Newly-diagnosed Polymyalgia Rheumatica and Giant Cell Arteritis

Actual Study Start Date :

Jun 3, 2022

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Outcome Measures

Primary Outcome Measures

Relapse (no/yes) of PMR/ GCA [Within one year after PMR/GCA diagnosis]
Relapse (no/yes) of PMR/ GCA (associated with endogenous cortisol levels under stable doses of 15 mg of prednisone). Relapse of GCA and or PMR is defined as intensification of immune-suppressive treatment due to symptoms, signs or laboratory values judged by the caring physician to be due to PMR or GCA.

Secondary Outcome Measures

Cumulative steroid dose at 1 year after diagnosis [At 1 year after diagnosis]
Cumulative steroid dose at 1 year after diagnosis
Number of patients with Tocilizumab or other immunosuppressive/ biological treatment started within 1 year after diagnosis. [Within one year after PMR/GCA diagnosis]
Number of patients with Tocilizumab or other immunosuppressive/ biological treatment started within 1 year after diagnosis.
Number of patients with Methotrexate (MTX) treatment started within 1 year after diagnosis [Within one year after PMR/GCA diagnosis]
Number of patients with Methotrexate (MTX) treatment started within 1 year after diagnosis
Prednisone/prednisolone ratio in plasma [Within one year after PMR/GCA diagnosis]
Prednisone/prednisolone ratio in plasma
Glucocorticoid Toxicity Index (GTI) at 1 year after diagnosis [At 1 year after diagnosis]
Glucocorticoid Toxicity Index (GTI) at 1 year after diagnosis. The GTI is composed of 9 domains and measures the change in glucocorticoid toxicity between 2 points in time. The GTI can measure not only the worsening of glucocorticoid toxicity but also its improvement. The minimal clinically important difference for the GTI scores is 10.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

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