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

NCT05479448 | Recruiting

• 1 other identifier: 2022-00788; mu22Daikeler
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Relapse (no/yes) of PMR/ GCA

  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.

  Within one year after PMR/GCA diagnosis

Secondary Outcomes (5)

• Cumulative steroid dose at 1 year after diagnosis

  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 Methotrexate (MTX) treatment started within 1 year after diagnosis

  Within one year after PMR/GCA diagnosis

• Prednisone/prednisolone ratio in plasma

  Within one year after PMR/GCA diagnosis

• Glucocorticoid Toxicity Index (GTI) at 1 year after diagnosis

  At 1 year after diagnosis

Interventions

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

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.

Data collection for exploratory analyses of endogenous steroid hormones OTHER

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

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

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.

Data collection for Prednisone metabolism OTHER

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• History of GCA and PMR in the past
• Inability to give informed consent

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Schweizerische Stiftung für die Erforschung der Muskelkrankheiten: collaborator
• Novartis: collaborator

Study Sites (1)

Department of Rheumatology University Hospital Basel

Basel, 4031, Switzerland

RECRUITING

MeSH Terms

Conditions

Polymyalgia Rheumatica; Giant Cell Arteritis; Glucocorticoid Receptor Deficiency

Interventions

Data Collection

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Vasculitis, Central Nervous System; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arteritis; Vasculitis; Skin Diseases, Vascular; Skin Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Thomas Daikeler, Prof. Dr. med.

  Department of Rheumatology University Hospital Basel

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Thomas Daikeler, Prof. Dr. med.

CONTACT

+41 61 265 27 09; Thomas.Daikeler@usb.ch

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: July 29, 2022
• Study Start: June 3, 2022
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: April 1, 2025

Record last verified: 2025-03

Locations

CH (1)