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

Giant Cell Arteritis (GCA) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05479448
• Other study ID #: 2022-00788; mu22Daikeler
• Status: Recruiting
• Start date: June 3, 2022
• Est. completion date: July 2024

Study information

• Verified date: August 2022
• Source: University Hospital, Basel, Switzerland
• Contact: Thomas Daikeler, Prof. Dr. med.
• Phone: +41 61 265 27 09
• Email: Thomas.Daikeler[@]usb.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Other:
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Switzerland	Department of Rheumatology University Hospital Basel	Basel

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Novartis, Schweizerische Stiftung für die Erforschung der Muskelkrankheiten

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cumulative steroid dose at 1 year after diagnosis	Cumulative steroid dose at 1 year after diagnosis	At 1 year after diagnosis
Secondary	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
Secondary	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
Secondary	Prednisone/prednisolone ratio in plasma	Prednisone/prednisolone ratio in plasma	Within one year after PMR/GCA diagnosis
Secondary	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