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

Abstract

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.

Seventy years after Hench’s Nobel prize: revisiting the use of glucocorticoids in systemic lupus erythematosus

“…evaluating 55 lupus patients found that patients receiving high-dose pulses (1 g/day for 3 days) had more frequent infections than those with lower doses (≤1500 mg for the three consecutive days). 42 Similar results were found in a recent study from Uruguay, showing lower rates of infections among patients treated with pulses of 500 mg or less each compared with 1000 mg. 43 In the RELES study, methyl-prednisolone pulses did not show an independent effect on the risk of infection; 36 however, they did in the GLADEL cohort. 37 As half the patients treated with pulses in the RELES cohort received less than 1000 mg/day for 3 days, 36 it is possible that the use of different doses of methyl-prednisolone explain the discrepancy.…”

Eosinophile Granulomatose mit Polyangiitis mit pulmonaler und kardialer Beteiligung

“…Methylprednisolon ist ein Standardmedikament zur Induktionstherapie diverser Autoimmunerkrankungen. Insbesondere der schnelle Wirkungseintritt begünstigt das Erreichen einer zügigen Remissionsinduktion [9]. Cyclophosphamid (CYC) ist bei eosinophiler Granulomatose mit Polyangiitis (EGPA) mit schwerer Organbeteiligung die Therapie der Wahl [10].…”

Glucocorticoids in Systemic Lupus Erythematosus. Ten Questions and Some Issues

“…The “classical” standard 1 mg/kg/day prednisone dose is not supported by either basic pharmacology or clinical evidence ( Figure 1 ) [ 19 , 20 ]. It is unlikely that anti-inflammatory effects increase significantly after prednisone doses have reached 30–40 mg/day, since such doses already result in a saturation of almost 100% of the genomic pathway [ 12 , 19 ].…”

“…The “classical” standard 1 mg/kg/day prednisone dose is not supported by either basic pharmacology or clinical evidence ( Figure 1 ) [ 19 , 20 ]. It is unlikely that anti-inflammatory effects increase significantly after prednisone doses have reached 30–40 mg/day, since such doses already result in a saturation of almost 100% of the genomic pathway [ 12 , 19 ]. Recent data suggest that higher initial doses of prednisone are associated with higher cumulative doses [ 21 ] with the well proven result of increasing damage accrual [ 1 , 22 , 23 , 24 , 25 ].…”

“…In 2018, Danza et al compared the efficacy and rates of infections among patients with several autoimmune conditions, including SLE, treated with MP pulses, for a total dose over three days ≤1500 mg, <1500 to ≤3000 mg and >3000 mg [ 19 ]. No differences among the different doses were seen in patients achieving complete response, partial response, or no response.…”