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

NCT ID: NCT05479448

Last Updated: 2025-04-01

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-06-03
• Study Completion Date: 2028-12-31

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).

Conditions

Polymyalgia Rheumatica (PMR); Giant Cell Arteritis (GCA)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Data collection for cellular analyses (Immune subset composition, GCR expression, in vitro steroid responsiveness)

Biological material will be sampled at three time-points. The first time-point will be when patients have been treated with 15 mg of prednisone per day for at least 5 days. A second time-point will be after prednisone was successfully tapered and maintained at 5 mg per day for at least 5 days, a third time point will be 4 weeks after the stop of prednisone. Biosampling is done for cellular analyses, pharmacokinetics and hormone measurements.

Intervention Type: OTHER

Data collection for exploratory analyses of endogenous steroid hormones

Concentrations of GC, MC, androgens and progestins will be determined and the suppression of cortisol and cortisone upon prednisone treatment will be analyzed.

Intervention Type: OTHER

Data collection for correlation between clinical defined and lab defined GC responsivness

The time to first relapse, the cumulative steroid dose at 1 year after diagnosis, the need for treatment with steroid sparing agents and the GTI after 1 year will be correlated to the percentage of in vitro inhibition of cytokine concentration by dexamethasone treatment, to the prednisone/prednisolone ratio in plasma, to the percentage of endogenous GC suppression (plasma and urinary cortisol and cortisone) by prednisone treatment. Furthermore, correlations of steroid sensitivity with Mineralocorticoid (MC) and androgens will be investigated.

Intervention Type: OTHER

Data collection for Prednisone metabolism

Plasma concentrations of prednisone and its active metabolite prednisolone will be quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). If changes on prednisone/prednisolone are observed, the quantification of the 6-hydroxylated prednisone/prednisolone metabolites in 24 h urine samples will be performed to estimate their metabolism as well as the ratio of inactive to active GC.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Schweizerische Stiftung für die Erforschung der Muskelkrankheiten

UNKNOWN

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Daikeler, Prof. Dr. med.

Role: PRINCIPAL_INVESTIGATOR

Department of Rheumatology University Hospital Basel

Locations

Department of Rheumatology University Hospital Basel

Basel, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Thomas Daikeler, Prof. Dr. med.

Role: CONTACT

Thomas.Daikeler@usb.ch

+41 61 265 27 09

Facility Contacts

Thomas Daikeler, Prof. Dr. med.

Role: primary

Thomas.Daikeler@usb.ch

+41 61 265 27 09

Other Identifiers

2022-00788; mu22Daikeler

Identifier Type: -

Identifier Source: org_study_id