Intravenous pulses of methylprednisolone to treat flares of immune-mediated diseases: how much, how long?

Introduction Glucocorticoids are widely used in the treatment of immune-mediated diseases. Despite their widespread use, details on dosing, effectiveness and adverse effects are yet to be determined. Objective To know the current use of methylprednisolone (MTP) in the management of immune-mediated conditions, evaluating the relationship among doses, therapeutic response and adverse effects. Methodology A multicenter retrospective cohort study was designed, including patients who received intravenous pulses of MTP between 1 January 2013 and 12 December 2015 in three different hospitals in Uruguay. The patients included received MTP to treat systemic autoimmune diseases (SADs), hematological, nephrological and neurologic diseases and others. The following variables were analyzed: age, gender, MTP cumulative dose, duration of treatment, clinical response (complete, partial and no response) and adverse effects. Results In total, 164 cases were identified, of which 118 (72%) were female. The median age was 48.4 (SD: 18) years. The indications for MTP included: neuroimmune-mediated 92 (56.1%), SADs 29 (17.5%), hematological 15 (9.1%), nephrological 12 (7.3%) and others 16 (9.9%). The median dose to achieve complete response was 3.2 g (SD: 1.5); the median dose to accomplish a partial response was 3.5 g (SD: 1.25); the median dose for non-responders was 3.3 g (SD 1.2) ( p > 0.05). The median dose in those patients with adverse effects was 3.4 g (SD 1.5) and the median dose for those who did not experience adverse effects was 3.3 g (SD: 1.3) ( p > 0.05). The most frequent adverse effects were infectious (22/164, 13.4%). Diabetics were found to have the highest incidence of adverse effects (13/16, 81%) in comparison to non-diabetics, p < 0.05. Discussion Our study suggests a wide range of doses and duration of treatments with MTP. No major associations were found between clinical response and the use of high MTP doses, but the latter was associated with a large proportion of severe infections. No severe infections were identified with MTP doses lower than 1.5 g. The diabetic population is known to be at risk of experiencing varied adverse effects to MTP. These observations reinforce the need for protocolized use of MTP in order to achieve a better relationship among doses, effectiveness and safety profile.

Cumulative dose of hydroxychloroquine is associated with a decrease of resting heart rate in patients with systemic lupus erythematosus: a pilot study.

INTRODUCTION: The use of hydroxychloroquine (HCQ) in patients with systemic lupus erythematosus (SLE) offers a wide range of benefits. However, there are evidence in favour of cardiotoxicity, including heart conduction disturbances and congestive heart failure. OBJECTIVE: To determine the effects of HCQ in the resting heart rate (RHR) of SLE patients. PATIENTS AND METHODS: Included were patients with non active SLE, with a sedentary lifestyle and treated with HCQ. Excluded were patients on beta blocker treatment, trained patients, pacemaker's users and patients with clinical or analytical evidence of anemia, renal disease, obstructive pulmonary disease, obesity, uncontrolled thyroid disease, fever or current infection. Standard 12-lead electrocardiogram was performed in the resting condition (supine decubitus and orthostatic position). Comparison between groups was performed using Mann-Whitney U test. A multiple linear regression was performed. A p value <0.05 was considered statistically significant. RESULTS: 42 patients were included. Patients were divided in two groups based on the cumulative dose of HCQ (CD-HCQ), considering 365 g as cut-off. There were 24 patients with low-HCQ (<365 g) and 18 patients with high-HCQ (>365 g). Non significant differences were found in age, sex, prednisone dose or SLEDAI. The mean RHR was 73 ± 6 beats/min in the low-HCQ and 65 ± 7 beats/min in the high-HCQ, with a significant decrease of 11% (p = 0.003). In multiple linear regressions, there were non significant association between the decrease of RHR and prednisone dose, age, SLEDAI or TSH, but there was significant association between RHR and CD-HCQ (p = 0.024) and RHR and time of exposure to HCQ (p = 0.029). CONCLUSION: CD-HCQ higher than 365 g was associated with a significant decrease (11%) in RHR in non-active SLE patients, although a larger prospective study is required to allow more definitive conclusions.

Hydroxychloroquine reduces low-density lipoprotein cholesterol levels in systemic lupus erythematosus: a longitudinal evaluation of the lipid-lowering effect.

UNLABELLED: The influence of antimalarials on lipids in systemic lupus erythematosus (SLE) has been identified in several studies but not in many prospective cohorts. The aim of this study was to longitudinally determine the effect of antimalarials on the lipoprotein profile in SLE. PATIENTS AND METHODS: Fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein cholesterol (LDL) plasma levels were determined at entry and after 3 months of hydroxychloroquine (HCQ) treatment in a longitudinal evaluation of 24 patients with SLE. RESULTS: a significant decrease in TC (198 ± 33.7 vs. 183 ± 30.3 mg/dl, p = 0.023) and LDL levels (117 ± 31.3 vs. 101 ± 26.2 mg/dl, p = 0.023) were detected after the 3 months of HCQ therapy. The reduction of 7.6% in TC (p = 0.055) and 13.7% in LDL levels (p = 0.036) determined a significant decrease in the frequency of dyslipidemia (26% vs. 12.5%, p = 0.013) after HCQ therapy. CONCLUSION: This longitudinal study demonstrated the beneficial effect of antimalarials on lipids in SLE since this therapy induced a reduction of atherogenic lipoproteins.