Biomarkers as predicting factors for relapse in polymyalgia rheumatica: the importance of alkaline phosphatase.

Abstract

Dear Editor, PMR is an inflammatory disease that affects older adults and causes pain and stiffness in the neck, shoulders and girdles. PMR is typically accompanied by the elevation of ESR or CRP [1]. Administration of a low–medium dose of steroid is recommended as initial therapy in the treatment of PMR without GCA [1]. Although clinical response is usually favourable, PMR relapses are frequent and have been reported in up to 67% of patients during the first year of follow-up and up to 49% of patients at 5 years [2]. Previous reports have suggested that the elevation of ESR or CRP [2, 3], and female [3], older [4] or heavier [5] patients might be a risk factor for PMR relapse; however, the characteristics underlying PMR relapse require elucidation. Herein, we assessed clinical and laboratory markers of PMR in cases of relapse. Data derived from the initial visit of all adult patients with PMR registered in the database of our hospital from July 2010 to October 2020 were retrospectively collected and analysed. All patients met Bird’s or 2012 ACR/EULAR criteria for PMR. Patients with a history or coexistence of GCA, patients who were suspected of having PMR initially, then whose diagnosis was changed from PMR to another (such as paraneoplastic syndrome), and patients with insufficient data were excluded. Patients who relapsed at least once were classified as the relapse group. We defined ‘relapse’ as a reappearance of clinical symptoms typically as PMR accompanied by an elevation of ESR (≥30 mm/h) or CRP (≥0.5 mg/dl) during the clinical course based on a previous report [2]. The univariate analysis between the relapse and non-relapse groups was performed using Fisher’s exact test (categorical variables) and Mann–Whitney U test (continuous variables). The cut-off for significant difference in the univariate analysis of new continuous variables was calculated using the following method. (i) The minimum to maximum values were separated by 5 and used as cut-off candidates. (ii) We binarized the candidates to above/below the value and added them to the established factors previously measured (age, sex, body weight, CRP and ESR) [2–5]. We created a logistic regression model using all the abovementioned factors as explanatory variables. (iii) Based on the prediction probability calculated from the model, the receiver operating characteristic (ROC) curve related to relapse/non-relapse was drawn, and the area under the curve (AUC) was calculated. (iv) By repeating these steps, the cut-off value candidate with the largest AUC was defined as the final cut-off value. Subsequently, we performed a multivariate logistic regression analysis. A P-value of <0.05 indicated statistical significance, and the adjusted odds ratio and corresponding 95% CI were subsequently estimated. A total of 72 patients were enrolled (Table 1). In total, 51 (70.8%) patients were women, and 31 (43.1%) had experienced a relapse. The univariate analysis revealed that age, sex and body weight did not show significant differences. ESR and serum alkaline phosphatase (ALP) were significantly higher in the relapse group than in the non-relapse group (96.0 vs 75.0 mm/h, P = 0.008; and 314.0 vs 253.0 U/l, P = 0.006, respectively). Although abdominal ultrasonography was performed in 11/72 (15.3%) cases, none revealed cholestatic liver diseases. Serum ALP was extracted as a new factor with a significant intergroup difference.