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

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.

Study Overview

• Status: Recruiting
• Conditions: Polymyalgia Rheumatica (PMR); Giant Cell Arteritis (GCA)
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Thomas Daikeler, Prof. Dr. med.; Phone Number: +41 61 265 27 09; Email: Thomas.Daikeler@usb.ch

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • Department of Rheumatology University Hospital Basel
    • Contact: Thomas Daikeler, Prof. Dr. med.; Phone Number: +41 61 265 27 09; Email: Thomas.Daikeler@usb.ch
    • Principal Investigator: Thomas Daikeler, Prof. Dr. med.
    • Sub-Investigator: Alex Odermatt, Prof. Dr. med.
    • Sub-Investigator: Christoph Berger, Prof. Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative steroid dose at 1 year after diagnosis	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.	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	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	Prednisone/prednisolone ratio in plasma	Within one year after PMR/GCA diagnosis
Glucocorticoid Toxicity Index (GTI) 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.	At 1 year after diagnosis

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Novartis; Schweizerische Stiftung für die Erforschung der Muskelkrankheiten
• Investigators: Principal Investigator: Thomas Daikeler, Prof. Dr. med., Department of Rheumatology University Hospital Basel

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2022
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 26, 2022
• First Submitted That Met QC Criteria: July 26, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): April 1, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: prednisolone; prednisone; Large vessel vasculitis (LVV); Glucocorticoid receptor (GCR); glucocorticoid (GC); steroid-response; GCR expression levels; GCR sensitivity/responsiveness; Swiss Clinical Quality Management in Rheumatic Diseases (SCQM); Glucocorticoid resistance; endogenous GC suppression
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Muscular Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Skin Diseases; Skin Diseases, Vascular; Vasculitis; Vasculitis, Central Nervous System; Polymyalgia Rheumatica; Giant Cell Arteritis; Arteritis; Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone; Hormones
• Other Study ID Numbers: 2022-00788; mu22Daikeler

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No