Steroid-related Adverse Events Research Articles

Timing of relapse as a key indicator of steroid-sparing requirements in childhood idiopathic nephrotic syndrome.

Managing children with frequent relapses or steroid-dependent nephrotic syndrome poses challenges due to recurrent relapses necessitating prolonged steroid exposure, thus increasing susceptibility to long-term complications. Identifying those at risk of poor response to steroid therapy may be helpful to guide timely intervention with steroid-sparing agents. This study aimed to identify factors associated with steroid-sparing agent needs in children with frequent relapses or steroid-dependent nephrotic syndrome. A retrospective multicenter cohort study was conducted by reviewing the medical records of children with idiopathic nephrotic syndrome treated between 2006 and 2023. Cox proportional regression analyzed prognostic factors for steroid-sparing agent requirements in children with frequent relapses or steroid-dependent nephrotic syndrome. The time-to-event analysis utilizing the Kaplan-Meier estimate examined the proportion of children needing steroid-sparing agents after diagnosis. Medical records of 121 children (85 males) diagnosed with idiopathic nephrotic syndrome at a median age of 4.5 years (range 1.3-12.8) were reviewed over a median follow-up of 3.7 years (range 1.0-15.0). Time to subsequent relapse post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis (at 3-month threshold) emerged as the sole significant predictor of steroid-sparing agent requirement, adjustedhazard ratio (aHR) = 2.26, 95% confidence interval (CI) 1.26-4.05. Kaplan-Meier analysis indicated that an earlier first relapse (< 3 months) led to earlier steroid-sparing agent requirement (log-rank p = 0.005). Children who relapsed within 3 months post-frequent relapses or steroid-dependent nephrotic syndrome diagnosis exhibited a higher frequency of relapses, a greater incidence of steroid-related adverse events, and were more likely to develop steroid dependency. Early subsequent relapse following diagnosis of frequent relapses or steroid-dependent nephrotic syndrome was linked to earlier requirement of steroid-sparing agent therapy. Further prospective research is necessary to confirm this observation.

Treatment strategies and treatment-related adverse events in MG according to the age of onset.

Early-onset (EOMG) and late-onset (LOMG) are distinct groups of MG patients. It is unclear if treatment strategies and treatment-related adverse events may differ according to the age of MG onset. This single-center retrospective study includes all MG patients followed at a tertiary center since 2007. We reviewed the electronic clinical records. In total, 212 patients were identified, 142 (67.0%) females, with a median disease duration of 10 years. The median age of symptom onset was 42.0 (26.0-64.5) years, with 130 (61.3%) EOMG cases and 82 (38.7%) LOMG. EOMG were more frequently female, had longer disease duration and often more generalized MG (p < 0.001). Comorbidities were significantly more frequent in LOMG (67.1%) compared to EOMG (53.1%) (p = 0.002). Steroid-related adverse effects motivating the switch to steroid-sparing agents (82.0%) were different between groups, with hypertension, hypercholesterolemia, diabetes mellitus and malignancies being more common in LOMG. At the same time, osteoporosis and dyspepsia were more frequent in EOMG (p < 0.001). The most common first-line choice was azathioprine (45.8%), and rituximab was used in 4 patients (1.9%). Our study shows that treatment modalities are similar between EOMG and LOMG, while steroid-related adverse events appear to be distinct.

IS INHALED CORTICOSTEROID STEP-DOWN RECOMMENDED FOR ADULT ASTHMA PATIENTS HAVE BEEN WELL CONTROLLED OVER THE LONG TERM WITH MODERATE OR HIGH-DOSE INHALED CORTICOSTEROIDS?

We conducted a systematic review to examine whether step-down of inhaled corticosteroid (ICS) is recommended for adult patients with asthma have been well controlled with moderate or high-dose inhaled corticosteroids for more than 12 weeks. Seven randomized controlled trials were included. ICS step-down did not increase asthma exacerbations requiring systemic steroid therapy and hospitalization. There was no effect on respiratory function, asthma control, or QOL. No significant differences were observed in serious adverse events or steroid-related adverse events, but the observation period was insufficient to assess long-term effects. Based on these results, we weakly recommend ICS step-down in adult patients with asthma have been well controlled with moderate or high-dose inhaled corticosteroids, but long-term asthma control and the incidence of steroid-related adverse events should be further investigated in the future.

SEVERE HYPOFIBRINOGENEMIA IN A PATIENT WITH GIANT CELL ARTERITIS TREATED WITH TOCILIZUMAB: CASE-BASED REVIEW

The Giant cell arteritis (GCA) is the most common form of systemic vasculitis in elderly patients. The treatment includes high doses of steroids and interleukin (IL)-6 inhibitor tocilizumab, especially in refractory or relapsing disease or in cases where there is an increased risk of steroid-related adverse events. This report discusses the case of a patient with giant cell arteritis who underwent treatment with tocilizumab for four years. The treatment was successful and resulted in clinical remission. However, four years after starting the therapy, the patient developed spontaneous hematomas on their extremities. After further investigation, it was discovered that the patient had developed thrombocytopenia and hypofibrinogenemia, which required substitution therapy. Malignancy and immune-mediated causes of hypofibrinogenemia and thrombocytopenia were ruled out. The patient experienced an extended period of hypofibrinogenemia that lasted for two months after the last dose of tocilizumab. During this time, the levels of CRP remained very low. This could be because the continued inhibition of IL-6 caused impaired hepatic synthesis of acute phase response proteins, which led to low fibrinogen and CRP levels in serum. The purpose of this case-based review is to emphasize the necessity of regular fibrinogen check-ups in GCA patients treated with tocilizumab.

Fifteen years of real-world data on the use of vigabatrin in individuals with infantile epileptic spasms syndrome.

This study was undertaken to evaluate our treatment algorithm for infantile epileptic spasms syndrome (IESS) used between 2000 and 2018. We initiated vigabatrin (VGB), and steroids were added if the electroclinical response (spasms and electroencephalogram [EEG]) to VGB was not obtained or incomplete. Individuals with IESS treated with VGB were recruited from our hospital clinical data warehouse based on electronic health records (EHRs) generated since 2009 and containing relevant keywords. We confirmed the diagnosis of IESS. Clinical, EEG, imaging, and biological data were extracted from the EHRs. We analyzed factors associated with short-term response, time to response, relapse, time to relapse of spasms, and the presence of spasms at last follow-up. We collected data from 198 individuals (female: 46.5%, IESS onset: 6 [4.5-10.3] months, follow-up: 4.6 [2.5-7.6] years, median [Q1-Q3]) including 129 (65.2%) with identifiable etiology. VGB was started 17 (5-57.5) days after IESS diagnosis. A total of 113 individuals were responders (57.1% of the cohort), 64 with VGB alone and 38 with VGB further combined with steroids (56.6% and 33.6% of responders, respectively). Among responders, 33 (29%) experienced relapses of spasms, mostly those with later onset of spasms (p = .002) and those who received VGB for <24 months after spasms cessation compared to a longer duration on VGB (45% vs. 12.8%, p = .003). At follow-up, 92 individuals were seizure-free (46.5% of the whole cohort), including 26 free of therapy (13.1%). One hundred twelve individuals (56.6%) were still receiving VGB, with a duration of 3.2 (1.75-5.7) years. Our sequential protocol introducing VGB then adding steroids is an effective alternative to a combined VGB-steroids approach in IESS. It avoids steroid-related adverse events, as well as those from VGB-steroid combination. According to our data, a period of 7 days seems sufficient to assess VGB response and enables the addition of steroids rapidly if needed. Continuing VGB for 2 years may balance the risk of relapse and treatment-induced adverse events.

Use of steroids in the management of low-risk myelodysplastic syndromes with autoimmune features.

The boundaries between myelodysplastic syndromes (MDS) and immune-mediated cytopenias are often difficult to establish and both conditions may benefit from immunosuppressive therapy. The optimal timing and doses of immunosuppressants are largely unknown. We systematically evaluated a retrospective cohort of 79 patients with low-risk MDS tested for anti-erythrocyte or anti-platelet autoantibodies to assess their frequency and the efficacy of immunosuppression, particularly with steroids. We found autoantibody positivity in 43% of cases and overt autoimmune diseases in 18%, including autoimmune hemolytic anemia, immune thromboctyopenia, and Evans syndrome. Steroid treatment improved cytopenia in about half of patients, with 26% achieving a complete recovery lasting for a median of 12 months. Better responses were observed in anemic patients with anti-erythrocyte autoantibodies than in those with anti-platelet autoantibodies, and the combination with recombinant erythropoietin (7/10) had a possible synergistic effect. Steroid doses were heterogeneous depending on the clinical intent (i.e., anti-inflammatory, immunosuppressive, anabolizing). Patients treated with a dose of 1 mg/kg day of prednisone for overt autoimmune cytopenia showed high rates of complete responses (60%). This observation suggests a trial with a short course (2-3 weeks) of standard steroid doses to ascertain efficacy and properly silence the autoimmune pathogenic mechanism. Steroid-related adverse events (16% of cases) should be monitored carefully in this elderly, frail population. In conclusion, features of autoimmunity are present in more than two-thirds of low-risk MDS patients and a trial with prednisone 0.5-1 mg/kg day for 2-3 weeks, with proper monitoring of adverse events, may be useful to improve cytopenias in selected cases.

Prophylactic use of steroids for a mucosal defect with a circumference of less than three-fourths prevents both symptomatic and asymptomatic stricture after esophageal endoscopic submucosal dissection.

Subclinical stricture after esophageal endoscopic submucosal dissection (ESD) makes the detection and re-ESD of metachronous lesions difficult. This study aimed to investigate the effectiveness of prophylactic steroid use after esophageal ESD for mucosal defects with a circumference less than 75% for the prevention of symptomatic and asymptomatic stricture. In 80 retrospectively enrolled patients, we collected paired endoscopic images of a mucosal defects immediately after resection and a scar thereafter. After calculating circumference by image analysis software, all patients were classified into three groups in reference to mucosal defect circumference (MDC; ≤ 50%, 50-75%, ≥ 75%). Frequency of steroid use and symptomatic stricture were compared, and in < 75% MDC patients, a degree of asymptomatic stricture with or without steroid was compared by calculating a scar contraction rate (SCR). In the ≤ 50% (43 patients), 50-75% (27 patients) and ≥ 75% (10 patients) MDC groups, steroids were used in 12%, 59% and 100%, respectively, and symptomatic stricture occurred in 0%, 7% and 40%, respectively. In < 75% MDC patients, SCR in the steroid cohort was significantly lower than that in the nonsteroid cohort (42% vs. 65%, p = 0.002). No steroid-related adverse events occurred. Steroid use even for mucosal defects with < 75% circumference appears effective for the reduction of the risk on both symptomatic and asymptomatic stricture after esophageal ESD.

Effectiveness of a two-year tapered course of tocilizumab in patients with giant cell arteritis: A single-centre prospective study

ObjectiveTo evaluate the feasibility of tocilizumab tapering and withdrawal in patients with giant cell arteritis (GCA). MethodsGCA patients eligible for tocilizumab were prospectively enrolled. Tocilizumab was administered weekly for the first 12 months, every-other-week for an additional 12 months, then discontinued. Relapses on tocilizumab were managed with temporary increases in systemic glucocorticoids or addition of methotrexate. Primary outcome was relapse-free survival at month 6 after tocilizumab suspension. Relapse-free survival on tocilizumab, imaging response, and adverse events were evaluated. Results23 GCA patients were enrolled. Reasons for tocilizumab start were relapse (n = 14), persistence of activity (n = 5), or steroid-related adverse events (n = 4). At tocilizumab start, two patients were on methotrexate, which was maintained. Fourteen patients had extracranial vascular involvement on 18FDG-PET/CT. During the first 12 months, four patients (17%) had clinical relapse. At every-other-week tocilizumab start, all patients were in clinical remission, two patients had active vasculitis on 18FDG-PET/CT; two patients were on steroid therapy, and four patients were taking methotrexate. Two patients (9%) relapsed while on every-other-week tocilizumab. At tocilizumab suspension, no patient was on steroid therapy and no patient had signs of active vasculitis on 18FDG-PET/CT. In the 6 months after tocilizumab discontinuation, six patients (26%) relapsed. No new or unexpected safety findings were identified. ConclusionTocilizumab tapered over a two-year period was effective to induce and maintain remission in GCA. Relapses on tocilizumab were minor and responded to incremental changes in therapy. A significant proportion of patients relapsed in the 6 months after therapy suspension.

Safety and Efficacy of Local Steroid Application on Dysphagia Following Anterior Cervical Discectomy and Fusion: A Systematic Review and Meta-analysis.

A systematic review and meta-analysis. To evaluate the safety and efficacy of local steroid application (LSA) on dysphagia after anterior cervical discectomy and fusion (ACDF). Dysphagia is one of the most common adverse events in the early postoperative period of ACDF. LSA is reported as an effective method to reduce the swelling of soft tissues, thereby decreasing the incidence of dysphagia. However, the safety and efficacy of LSA on dysphagia after ACDF need to be systematically reviewed and analyzed. A comprehensive literature search was carried out in the database PubMed, Web of Science, EMBASE, Clinical key, Cochrane library, and Wiley Online Library to screen papers that report LSA in ACDF surgery. The Cochrane Collaboration tool and a methodological index for nonrandomized studies were used for the assessment of study quality. Data were analyzed with the Review Manager 5.3 software. A total of 10 studies were included. The results revealed no significant differences between the steroid group and the control group in ACDF regarding postoperative drainage, estimated blood loss, and neck disability index score ( P > 0.05). LSA significantly alleviates visual analog scale score for neck pain (or odynophagia) ( P < 0.05), reduces the length of hospital stay (weighted mean difference, -1.00 (-1.05 to -0.95); P < 0.001), and mitigates dysphagia rate and prevertebral soft-tissue swelling in the early postoperative period ( P < 0.05). There seemed to be no significant increase in the complication rate and steroid-related adverse events in the steroid group compared with the control group ( P < 0.05). LSA shows advantages in reducing the length of hospital stay, decreasing dysphagia rate, and mitigating prevertebral soft-tissue swelling in the early postoperative period of ACDF. Further large-scale studies are urgently required for the development of a standard protocol for LSA and further analysis of potential delay complications.

Efficacy and steroid-sparing effect of tacrolimus in patients with autoimmune cytopenia

The aim of this study was to evaluate the efficacy, safety, and steroid-sparing effect of tacrolimus in patients with autoimmune cytopenia, including immune thrombocytopenia (ITP), autoimmune hemolytic anemia (AIHA), and Evans syndrome (ES). Patients in the tacrolimus group were treated with tacrolimus in combination with steroids, and the control group received only steroids. Of the 318 patients finally enrolled, 87 (27.4%) were males, with a median age of 45 (14-90) years. The tacrolimus group comprised 144 patients, including 120 ITP, 19 AIHA, and 5 ES patients, and the control group comprised 174 patients, including 141 ITP, 25 AIHA, and 8 ES patients. The optimal ORR of the tacrolimus group was comparable to that of the control group, and the optimal CRR was higher (p < 0.05). Patients receiving tacrolimus had a decreased relapse rate and prolonged relapse-free survival (p < 0.05) compared with the controls for both the whole cohort and the ITP and AIHA subgroups. Compared with the control group, the tacrolimus group had a lower cumulative steroid dosage and earlier discontinuation of steroids (p < 0.05), which resulted in a decreased incidence of steroid-related adverse events (p < 0.05) although the total side effects were similar between the two groups. Similar drug expenses were observed between the tacrolimus and control groups at the 18-month follow-up. In conclusion, the early addition of tacrolimus had a similar ORR, better CRR, lower relapse rate, and prolonged relapse-free survival compared to steroids alone, with reduced steroid-related adverse events.

POS0266 EFFECTIVENESS OF A SPACING-UP STRATEGY AFTER ONE-YEAR COURSE OF WEEKLY TOCILIZUMAB IN PATIENTS WITH GIANT CELL ARTERITIS: A SINGLE-CENTRE PROSPECTIVE STUDY

BackgroundAlthough tocilizumab (TCZ) is extensively used for the treatment of giant cell arteritis (GCA), there is still uncertainty with regard to optimal treatment duration. The GiACTA open-label extension phase showed that 58% of patients treated with a 12-month course of weekly TCZ had a disease flare in the 2 years following therapy suspension1, suggesting that some patients may need a more prolonged duration of this therapy.ObjectivesTo evaluate efficacy and safety of low-dose TCZ maintenance in GCA patients who achieved remission after one year of standard TCZ therapy.MethodsGCA patients eligible for TCZ according to the 2018 EULAR recommendations2 and who achieved remission after one year of weekly subcutaneous TCZ were prospectively enrolled. TCZ was administered every-other-week (EOW) for additional 12 months, and eventually suspended. Patients were evaluated 4-monthly during TCZ therapy, and 1 and 6 months after TCZ suspension (Figure 1). In patients with large-vessel (LV) involvement at baseline, PET scan was performed 12 and 24 months after TCZ start. Primary outcome was relapse-free survival at month 6 since TCZ suspension. Relapse-free survival during TCZ therapy and imaging response at PET scan were also evaluated. Adverse events were recorded.Figure 1.Study design.Results17 patients were enrolled (12 women, 71%; mean age 71.5±8.7 years). Disease features at diagnosis and TCZ start are listed in Table 1. Reasons for TCZ start were clinical or imaging disease flare (n=9), persistence of disease activity (n=5), and steroid-related adverse events (n=3). At TCZ start, median disease duration was 8 (3-22) months, serum C-reactive protein (CRP) was 13 (6-22) mg/L, daily prednisone (PDN) dose was 25 (15-37.5) mg; 4 patients were already on methotrexate (MTX) which was maintained in 1 of them; 10 patients (59%) had LV involvement on PET scan. At TCZ EOW start, no patient was on PDN and 1 patient was on MTX; MTX was added in another patient due to persistence of LV involvement at PET scan. All patients completed the 24-month TCZ course. Two patients (12%) had a polymyalgic flare while on EOW TCZ: one patient at month 1 and one patient at month 6; of note, one of them had a polymyalgic flare also while on weekly TCZ. Both flares were managed with a PDN course with complete clinical remission. No patient had active LV involvement at 24-month PET scan. Adverse events on EOW TCZ were zoster reactivation (n=1) and neutropenia (n=1). At TCZ stop, no patient was on PDN and 2 patients were on MTX. One month after TCZ stop, all patients were in remission. Six months after TCZ stop, 4 patients (24%) experienced a flare, which was successfully managed in all cases with TCZ weekly re-introduction; in 2 patients, a PDN course was also started.Table 1.Patients’ characteristics at giant cell arteritis diagnosis and at study entry.GCA diagnosis, n=17n (%)TCZ start, n=17n (%)Headache16 (94)5 (29)Scalp tenderness11 (65)5 (29)Jaw claudication9 (53)2 (12)Ocular ischemic manifestations3 (17)0 (0)Polymyalgia rheumatica8 (47)0 (0)Constitutional symptoms14 (82)7 (47)Active vasculitis on PET10 (59)10 (59)Modality of diagnosisVascular ultrasound7 (47)-Temporal artery biopsy3 (17)-PET10 (59)10 (59)ConclusionIn this proof-of-concept study, low-dose TCZ maintenance in GCA showed excellent disease control, which was maintained in most patients after therapy suspension. Longer follow-up and replication in larger cohorts are required.

Steroid-Resistant Central Nervous System Sarcoidosis: The Selections of Multi-Agent Combination as the Initial Treatment

Sarcoidosis is a granulomatous multiorgan disease of unknown etiology that commonly affects the respiratory system, eyes, and skin, and less commonly affects the nervous system. Because of its rarity, a standard treatment for central nervous system (CNS) sarcoidosis has not yet been established. Corticosteroids remain the cornerstone of CNS sarcoidosis treatment. However, CNS sarcoidosis, other than isolated facial nerve paralysis, is often refractory to treatment and requires long-term corticosteroid treatment. In particular, patients with hydrocephalus have a high mortality rate and a lack of response to this treatment. Therefore, immunosuppressants, including TNF-α inhibitors and corticosteroids, should be considered as the initial treatment. For older patients, it is important to pay attention to infection as an adverse event and to the toxicity of the therapeutic agents. Because steroid-related adverse events are more common in the older patient group, the lowest effective dose should be used, and the treatment duration should be kept as short as possible after careful evaluation of disease activity. Corticosteroid-sparing agents are effective at reducing the cumulative toxicity of corticosteroids. Recently, various new potential agents have emerged and their efficacy has been assessed. It is expected that more treatment options will be available for CNS sarcoidosis in future.

Ocular Toxicity of Belantamab Mafodotin, an Oncological Perspective of Management in Relapsed and Refractory Multiple Myeloma.

Belantamab mafodotin (belamaf), an antibody-drug conjugate approved for the treatment of relapsed and refractory multiple myeloma (RRMM), is an anti B-cell maturation antigen (BCMA) agent. DREAMM-1, a first in-human trial of belamaf, reported several ocular toxicities requiring dose adjustments, dose delays and treatment discontinuations. In DREAMM-1, 53% of patients in part-1 and 63% of patients in part-2 had ocular toxicity. Similarly, 73% of patients in DREAMM-2 had keratopathy (71% in 2.5 mg/kg versus 75% in 3.4 mg/kg) with the most common symptoms being blurred vision and dry eyes. Ocular toxicity of belamaf is attributed to microtubule-disrupting monomethylauristatin-F (MMAF), a cytotoxic payload of the drug that causes an off-target damage to the corneal epithelial cells. Ocular adverse events (AEs) of belamaf are more frequent at higher doses compared with lower doses. Higher belamaf dose, history of dry eyes and soluble BCMA are associated with increased risk of corneal toxicity. Absence of ocular symptoms does not exclude the possibility of belamaf-induced ocular toxicity, so patients need slit lamp and Snellen visual acuity testing to detect microcytic-like epithelial changes and visual decline. Corticosteroid eyes drops for 4-7 days prior to belamaf dose do not prevent ocular AEs and may cause steroid-related AEs instead. Keratopathy and Visual Acuity scale (KVA) is recommended to document the severity of belamaf-induced ocular toxicity and make treatment adjustments. Management of toxicity includes dosage modifications, treatment interruption or discontinuations and preservative-free artificial tears along with close ophthalmology and hematology-oncology follow-ups.

High-dose glucocorticoids pulse-therapy for beta-coronaviridae pneumonia: a systematic literature review and case-series of Coronavirus disease-2019.

The results of the RECOVERY trial identified dexamethasone as the first pharmacological therapy that reduces mortality in patients with COVID-19. The aim of this paper is to conduct a systematic literature review on safety and efficacy of pulse glucocorticoid therapy for Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV), Middle East Respiratory Syndrome (MERS)-CoV or SARS-CoV-2 infections and describe a case-series of COVID-19 patients treated with off-label pulse doses of methylprednisolone. We performed a systematic literature review on safety and efficacy of pulse therapy for betacoronaviridae infections as described in the protocol registered on PROSPERO (CRD42020190183). All consecutive patients admitted to Arcispedale Santa Maria Nuova di Reggio Emilia or Guastalla Hospital with COVID-19 between March 1st and April 30th, 2020 and treated with methylprednisolone 1 gram/day for at least three days were included in the case series. A retrospective review of available computed tomography (CT) scan and chest x-ray was performed independently by two radiologists blinded to clinical data, and discordances were resolved by consensus. Twenty papers were included for SARS, but only two were comparative and were included in the primary endpoint analysis. Likewise, eleven papers were included for COVID-19, four of which were comparative and were considered for the primary outcome analysis. Included studies for both SARS and COVID-19 are mostly retrospective and highly heterogeneous, with lethality ranging from 0% to 100% and ICU admission rate ranging from 9% to 100%. Fourteen patients were included in our case series, 7 males and 7 females. No randomised controlled trial is available yet for corticosteroids pulse-therapy defined as at least ≥500mg/day methylprednisolone in patients with emerging coronavirus pneumonia. Lethality among our cohort is high (4/14), but this finding should be interpreted with caution due to the fact that in our setting pulse-steroids were used in patients not eligible for other treatments because of comorbidities or as rescue therapy. The incidence of steroid-related adverse events seems low in our cohort. The quality of the evidence on glucocorticoid pulse-therapy in SARS, MERS and COVID-19 is poor. Randomised controlled trials are greatly needed.

Treatment of idiopathic nephrotic syndrome with two steroid dosing regimens - one-year observational study.

IntroductionThe aim of the study was to compare the first year of disease in children with idiopathic nephrotic syndrome (INS) treated according to two prednisone dosing regimens: a weight-based schedule (2 mg/kg/24 h in the 1st month, 2 mg/kg/48 h in the 2nd month, with dose tapering during the following 4 months), and a body surface area (BSA)-based schedule (60 mg/m2/24 h in the 1st month, 40 mg/m2/48 h in the 2nd month, with dose tapering during the following 4 months).Material and methodsIn 2 groups of children treated with weight- and BSA-based regimens (20 patients, 3.13 ±1.01 years, treated in 2010-2013 and 20 patients, 5.13 ±2.86 years, treated in 2014-2016) clinical and anthropometrical parameters, number of INS relapses, total prednisone dose (mg/kg/year), and steroid adverse effects were compared during the first year of disease.ResultsChildren treated with the weight-based steroid regimen received a higher total annual prednisone dose (259.06 ±79.54 vs. 185.83 ±72.67 mg/kg/24 h, p = 0.004) and had a shorter (though not significantly) period without prednisone (38.25 ±55.83 vs. 75.90 ±73.06 days, p = 0.062) compared to patients treated with the BSA-based regimen. There was no difference in number of relapses between groups (2.20 ±1.64 vs. 1.60 ±1.67, p = 0.190) but more patients relapsed in the weight-based group (19/20 vs. 13/20, p = 0.044). No differences in Z-score values of height, weight, and body mass index (BMI) were observed. No steroid-related adverse events were noted except for arterial hypertension (4/20 vs. 5/20 patients, p = 1.000).ConclusionsThe BSA-based regimen of prednisone dosing in children with INS reduces exposure to steroids and risk of relapse, as well as increases days off steroids in the first year compared to the weight-based regimen with a high second-month dose.

P0366SAFETY OF STEROID THERAPY IN IGA NEPHROPATHY: THE CLINICAL EXPERIENCE OF 48 NEPHROLOGY UNITS IN ITALY

Abstract Background and Aims Steroid therapy is efficient in inducing remission of IgA nephropathy (IgAN) and preventing end stage renal disease (ESRD) but there are concerns about their safety. The TESTING trial in particular has been stopped early because of a higher incidence of side effects than conservative treatment thus inducing a conservative therapy with RAAS (renin angiotensin antagonist system) blockers. The aim of this analysis was to evaluate the incidence of adverse events (AE) in a retrospective observational trial on the real clinical practice. Method We evaluated 1209 patients (pz) with IgAN coming from 48 Italian centers: 285 pz in RAAS blockers alone, 732 treated for 6 months with steroid and 192 with a combination of steroid and other immunosuppressants (also with RAAS blockers). The analysis was limited to the 6 months of therapy. Results The basal characteristics of the 3 groups are shown in the table below. The figure shows the frequencies of 69 adverse events related with immunosuppression: the most frequent were infections (23, 2.73% of all patients, 34.3% of all AE), impaired glycemic control (11, 0.91% of patients, 16% of all AE), severe hypertension (6, 8.7% of all AE) and leukopenia (9, 0.80% of patients, 13% of all AE). Infections were observed in 16 (2.19%) pz in steroid therapy and 7 (3.65%) pz in steroid+immunosoppressive treatment. Liver toxicity and and gastrointestinal AE were observed almost in pz receiving steroid+ immunosuppressants [1(0.14%) and 2 (1.04%) pz, respectively]. 7 pz in steroid therapy (0.96%) and 2 in steroid+ immunosuppressants experienced an impaired glycemic control. All the 9 cases of leucopenia were registered in pz in steroid+ immunosuppressants (4.69%). A slightly higher incidence of allergies was observed in the RAAS blocker group (20 cases, 0.7%). The higher rates of infections and leucopenia were observed in pz above 70 years of age (6.12%,p&amp;lt;0.05), as higher incidence of infections and impaired glycemic control were registered in pz with an eGFR&amp;lt;30 ml/min/1.73 m2 (4.64 and 1.99%,p&amp;lt;0.05). Severe hypertension and leucopenia were observed respectively in 9 and 3 pz with an eGFR &amp;lt;60 ml/min/1.73m2. No significant relationships were found between AE, proteinuria and sex. Multivariate logistic regression showed an independent association of immunosuppressive treatment and age with any AE [ODDS ratio: 3,35 (CI:2,18-5,14) and 1,02 (CI:1,01-1,04), respectively; p&amp;lt;0.05]. Death occurred for sepsis in a 70 years old pz (eGFR=21.7 ml/min/m2, 24hproteinuria=16.1 g/day) after 3 months of treatment. Conclusion the incidence of EA in our observational study is lower than that observed in the TESTING and STOP trials (5.71% vs 14.7% and 40%, respectively). The most frequent AE were almost observed in oldest subjects with impaired renal function on steroid+other immunosuppressants. Though this trial is not randomized nor controlled (RC), it considers a large cohort of pz coming from the real clinical practice of the Italian Nephrology Units and demonstrates that the significantly lower incidence of steroid related AE than that observed in some RC trials doesn’t justify the abstention from steroids in IgAN at risk of progression. Much more attention should be paid in elderly pts with severe renal dysfunction with a closer follow-up, dose adjustments and antibiotic prophilaxis.

Corrigendum: Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial.

Background and Aims Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. Methods This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. Results In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. Conclusions In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial.

Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

Open-Label, Observational Pilot Study Evaluating Desoximetasone Topical Spray 0.25% Twice Daily in Patients With Psoriasis Being Treated With Biologic Agents

Biologic therapy has been an important addition to the armamentarium of psoriasis drugs as they offer high efficacy with a better side effect profile than systemic agents. However, there are cases in which patients do not respond rapidly or lose their initial response to biologic therapy, thus requiring additional treatment. While biologic therapy could be switched from one agent to another, in many cases, patients have had no adverse events (AEs) and the remaining lesions are minimal. In such cases, the addition of a topical agent may be the best choice. This single-center, open-label observational study enrolled 20 patients ≥18 years of age with plaque psoriasis with ≤5% body surface area (BSA) involvement. Patients received biologic therapy for at least 24 weeks prior to baseline. Topical combination therapy with desoximetasone spray 0.25% was added twice daily for 4 weeks and then decreased to twice-daily application on 2 consecutive days per week to week 16. Topical therapy was effective and well tolerated. Body surface area decreased −1.20 by week 4. Physician global assessment (PGA) score improved by −1.10 at week 4 and by −1.50 at week 16. The mean BSA × PGA score was 8.85 at baseline and had declined by −4.90 by week 4, an effect that was maintained to week 16. The combination therapy was well tolerated and safe. There were no AEs considered related to study medications and no steroid-related AEs such as atrophy, striae, telangiectasia, or folliculitis. Patients showed improvements in dermatology quality of life questionnaire scores. A treatment satisfaction questionnaire showed that overall patients were satisfied with the treatment regimen and found it to be convenient at all time points.

Treatment of pediatric cerebral radiation necrosis: a systematic review.

Cerebral radiation necrosis (CRN) is a toxicity of radiation therapy that can result in significant, potentially life-threatening neurologic deficits. Treatment for CRN has included surgical resection, corticosteroids, hyperbaric oxygen therapy (HBOT), and bevacizumab, but no consensus approach has been identified. We reviewed the available literature to evaluate efficacy of treatment approaches. Using methods specified in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines when possible, we conducted searches of Ovid MEDLINE, Embase and Pubmed to identify studies reporting on outcomes for children (≤21years old) with CRN. Eligible studies from 1990 to 2014 describing central nervous system (CNS) radiation necrosis with details of both treatment and outcomes were included. Eleven studies meeting criteria were identified. Of the nine studies with total patient denominators, 37 of 806 patients developed CRN (incidence = 4.6 %). Patients received treatment courses of steroids alone (n = 13), steroids with bevacizumab (n = 11) or HBOT (n = 12). Patients who failed to respond to steroids were more likely to be older than steroid-responsive patients (p = 0.009). With the exception of steroid-related adverse events, there was only one report of an adverse event (brainstem stroke) potentially attributable to intervention (bevacizumab). Those who received proton beam RT were both younger (p = 0.001) and had a shorter time to development of CRN (p = 0.079). The most common treatment following steroid initiation was addition of bevacizumab or HBOT, with good success and minimal toxicity. However, randomized controlled trials are needed to establish a definitive treatment algorithm that can be applied to children affected by CRN.