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.
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
Treatment with Tocilizumab, MTX or other disease modifying medications at inclusion
History of GCA and PMR in the past
Inability to give informed consent
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.
Cohort
Prospective
Data collection for cellular analyses (Immune subset composition, GCR expression, in vitro steroid responsiveness)
Other interventionBiological 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 interventionConcentrations 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 interventionThe 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 interventionPlasma 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.
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.
Cumulative steroid dose 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.
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
Number of patients with Methotrexate (MTX) treatment started within 1 year after diagnosis
Prednisone/prednisolone ratio in plasma
Prednisone/prednisolone ratio in plasma
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University Hospital, Basel, Switzerland
Lead sponsor
Schweizerische Stiftung für die Erforschung der Muskelkrankheiten
Collaborator
Novartis
Collaborator
