Sarcoidosis and calcium homeostasis disturbances-Do we know where we stand?

The majority of cases involving hypercalcemia in the setting of sarcoidosis are explained by the overproduction of calcitriol by activated macrophages. Vitamin D takes part in the regulation of granuloma formation. However, using vitamin D metabolites to assess the activity of the disease is still problematic, and its usefulness is disputable. In some cases, though, a calcium metabolism disorder could be a valuable tool (i.e. as a marker of extrathoracic sarcoidosis). Although sarcoidosis does not cause a decrease in bone mineral density, increased incidence of vertebral deformities is noted. Despite increasing knowledge about calcium homeostasis disorders in patients with sarcoidosis, there is still a need for clear guidelines regarding calcium and vitamin D supplementation in these patients.

Effectiveness and tolerability of methotrexate in pulmonary sarcoidosis: A single center real-world study.

Background: Pulmonary sarcoidosis patients who get disease progression despite corticosteroid treatment or can't tolerate corticosteroid required second-line drug. Methotrexate (MTX) is the most widely used in our clinical practice. Data on its safety and efficacy at different doses are still limited, especially for those without folic acid supplements. Objective: To report effectiveness of different MTX dosages and tolerability of MTX in pulmonary sarcoidosis without folic acid supplements. Methods: A retrospective study on pulmonary sarcoidosis patients receiving MTX therapy with various dose ≥3 months was conducted. The primary outcome was change in high-resolution computed tomography (HRCT) before and after MTX therapy. Other efficacy parameters included SGRQ score, prednisone dose change, discontinuation and relapse-free survival. Response-linked factors and safety outcomes were also analyzed. Results: Overall, 49 patients (81.7%) were assessed as MTX responders by HRCT and there was no significant difference in clinical response rate among three groups with different doses. The health-related quality of life (HRQL) of the responders improved obviously, which was evidenced by SGRQ score declining from 16.7(IQR: 7.9-26.4) to 10.7(IQR: 4.8-19.3) (P=0.029). The corticosteroids sparing effect was confirmed in "responders" group (P<0.001). When MTX was discontinued in 11 responders with complete improvement, 2 patients experienced relapses within 15.5 (range: 1-30) months (mean follow-up time of these 11 responders: 13.5±13.0 months). No clinical characteristics were found related to MTX effectiveness. Adverse events occurred in 31.7% of the patients, with gastrointestinal-related being the commonest. Drug discontinuation owing to adverse events occupied 6.7% of the subjects. Conclusions: Nearly 80% of the sarcoidosis subjects had well response to MTX. Its effectiveness was irrelevant to the treatment dosages and baseline characteristics. A quite low relapse rate was witnessed in those complete responders discontinuing MTX therapies. The steroid-sparing effect, well drug tolerability and low drug withdrawal rate were observed in these patients even without folic acid supplements in clinical practice.

Efficacy and safety of infliximab biosimilar Inflectra® in severe sarcoidosis.

BACKGROUND: Infliximab, a monoclonal antibody against tumor necrosis factor alpha (TNF-α) is effective third-line therapy in severe sarcoidosis. The originator product of Infliximab, Remicade®, is expensive, limiting universal access. Recently, a less expensive biosimilar of infliximab, Inflectra®, has become available, but the efficacy and tolerability has not been studied in sarcoidosis. METHODS: In this retrospective cohort study, 29 patients treated with the infliximab biosimilar Inflectra®, were analysed. Patients received Inflectra® intravenously monthly at a dose of 5 mg/kg. We measured trough levels before every infusion. Before and after 6 months of induction therapy pulmonary function and disease activity were evaluated using Standardised Uptake Value (SUV) of the 18F-fluorodeoxyglucose by positron emission tomography (18F-FDG PET), soluble interleukin-2 receptor (sIL-2R), angiotensin converting enzyme (ACE) and health-related quality of life (HRQOL). RESULTS: In patients with pulmonary sarcoidosis as main treatment indication (n = 15) the predicted FVC improved with 8.1%, p < 0.05. Furthermore, in the whole group HRQoL improved significantly (p < 0.001), whereas SUVmax and sIL-2R significantly reduced (p < 0.001 and p = 0.001 respectively). Hospitalisation due to infections occurred in four patients. None of the patients discontinued Inflectra® due to side-effects. Furthermore, all patients had detectable trough levels indicating development of neutralizing antibodies. CONCLUSION: Infliximab biosimilar Inflectra® seems effective in the treatment of refractory sarcoidosis with a comparable safety profile to the reference product Remicade®. Inflectra® can be considered as an alternative and less expensive option for patients with refractory sarcoidosis.

The effect of corticosteroids on quality of life in a sarcoidosis clinic: the results of a propensity analysis.

BACKGROUND: Both sarcoidosis and its treatment may worsen health related quality of life (HRQoL). We performed a propensity analysis of sarcoidosis-specific HRQoL patient reported outcome measures (PRO) to disentangle the effects of sarcoidosis and corticosteroid therapy on HRQoL in sarcoidosis outpatients. METHODS: Consecutive outpatient sarcoidosis patients were administered modules from two sarcoidosis-specific HRQoL PROs: the Sarcoidosis Health Questionnaire (SHQ) and the Sarcoidosis Assessment Tool (SAT). Patients were divided into those that received ≤500 mg of prednisone (PRED-LOW) versus >500 mg of prednisone (PRED-HIGH) over the previous year. SAT and SHQ scores were initially compared in the two corticosteroid groups. Then a multivariate analysis was performed using a propensity score analysis adjusted for race, age, gender and the severity of illness. RESULTS: In the unadjusted analysis, the PRED-HIGH group demonstrated the following worse HRQoL scores compared to the LOW-PRED group: SHQ Daily (p = 0.02), SAT satisfaction (p = 0.03), SAT daily activities (p = 0.03). In the propensity analysis, the following domains demonstrated worse HRQoL in the PRED-HIGH group than the PRED-LOW group: SAT fatigue (p < 0.0001), SAT daily activities (p = 0.03), SAT satisfaction (p = 0.03). All these differences exceeded the established minimum important difference for these SAT domains. The SHQ Physical score appeared to demonstrate a borderline improved HRQoL in the PRED-HIGH versus the PRED-LOW group (p = 0.05).). In a post-hoc exploratory analysis, the presence of cardiac sarcoidosis may have explained the quality of life differences between the two corticosteroid groups. CONCLUSIONS: Our cohort of sarcoidosis clinic patients who received ≤500 mg of prednisone in the previous year had an improved HRQoL compared to patients receiving >500 mg on the basis of two sarcoidosis-specific PROs after adjusting for severity of illness. These data support the need to measure HRQoL in sarcoidosis trials, and suggest that the search should continue for effective alternative medications to corticosteroids.

Bone density is normal and does not change over 2 years in sarcoidosis.

SUMMARY: Small studies have previously suggested that sarcoidosis may be associated with low bone mineral density. In this observational study of 64 patients with sarcoidosis, bone mineral density was within the normal range at baseline, and there was no evidence of accelerated bone loss over 1-2 years. INTRODUCTION: Several small studies have suggested that sarcoidosis may be associated with low bone mineral density (BMD). METHODS: We undertook a cross-sectional study of BMD in 64 patients with sarcoidosis. Of these, 27 with 25-hydroxyvitamin D<50 nmol/L entered a 1-year intervention study of vitamin D supplements, and 37 entered a 2-year longitudinal study of BMD, with the primary endpoint of the change in lumbar spine BMD. RESULTS: The mean age of participants was 58 years, 68% were female, and 8% were currently using oral glucocorticoids. At baseline, BMD for the entire cohort was greater than the expected values for the population at the lumbar spine (mean Z-score 0.7, P<0.001) and total body (0.5, P<0.001) and similar to expected values at the femoral neck (0.2, P=0.14) and total hip (0.2, P=0.14). BMD did not change at any of these four sites (P>0.19) over 2 years in the longitudinal study. In the intervention study, vitamin D supplements had no effect on BMD, and therefore we pooled the data from all participants. BMD did not change over 1 year at the spine, total hip, or femoral neck (P>0.3), but decreased by 0.7% (95% confidence interval 0.3-1.1) at the total body (P=0.019). CONCLUSIONS: BMD was normal at baseline, and there was no consistent evidence of accelerated bone loss over 1-2 years, regardless of baseline vitamin D status. Patients with sarcoidosis not using oral glucocorticoids do not need routine monitoring of BMD.

No effect of high-dose inhaled steroids in pulmonary sarcoidosis: a double-blind, placebo-controlled study.

OBJECTIVE: To evaluate whether inhaled steroids in high doses might be of therapeutic value in pulmonary sarcoidosis. DESIGN: Randomized, double blind and placebo controlled parallel study. SETTING: The out-patient clinic of the Department of Pulmonary Medicine, Gentofte Hospital, Copenhagen, Denmark. SUBJECTS: Twenty-one untreated patients (17 males, 4 females, median age 33 years, range 21-65) and eight patients treated with systemic prednisolone. All patients had biopsy proven pulmonary sarcoidosis radiological stage I-III. INTERVENTIONS: Treatment with either inhaled budesonide 1.2 mg day-1-2.0 mg day-1 (n = 9) or placebo (n = 12) for 12 months. MAIN OUTCOME MEASURES: Clinical (cough, chest pain, dyspnoea) and paraclinical variables (chest X-ray, gallium scintigraphy, pulmonary function tests, and biochemical markers of disease activity: blood leukocytes, lymphocytes, serum (S-) angiotensin converting enzyme (ACE), S-1,25-OH-cholecalciferol, plasma (P-) calcium, P-immunoglobulins) were recorded before treatment, every three months during treatment, and 6 months after treatment had been discontinued. RESULTS: There were no significant differences between the recorded variables in the budesonide and placebo groups. In general, a regression of disease activity was observed in both groups. Two patients in the treatment group, treated with 2.0 mg budesonide/day, and two in the placebo group had progression in disease and were put on systemic steroids. CONCLUSION: Inhaled budesonide in doses of 1.2-2.0 mg day-1 had no recognizable therapeutic effect on pulmonary sarcoidosis.