Tapering Of Oral Corticosteroids Research Articles

Steroid response encephalopathy associated with autoimmune thyroiditis

IntroductionSteroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a rare autoimmune disorder affecting the central nervous system, characterized by a spectrum of neurological and psychiatric symptoms.AimThis case study aims to highlight the diagnostic challenges and the successful management of SREAT syndrome in a young woman with autoimmune thyroiditis.Case studyA 21-year-old woman with documented Hashimoto's thyroiditis and polycystic ovary syndrome was admitted to the Clinic of Neurology following a 5-minute tonic seizure and subsequent confusion state lasting several hours. Initial brain MRI showed no abnormalities, and EEG revealed generalized slowness. Comprehensive laboratory assessments, including a complete blood count, biochemical analysis, and electrolyte panels, all yielded normal results. Further investigation revealed a significantly elevated anti-thyroid peroxidase antibody (anti-TPO) titer exceeding 1000 IU/mL. The suspicion of SREAT syndrome was considered. Pulse therapy with methylprednisolone was associated with rapid recovery. The patient was discharged from the hospital with an oral corticosteroid tapering regimen.Results and discussionThe administration of pulse therapy with methylprednisolone resulted in a rapid and very good response in the patient, evidenced by the resolution of seizure activity and improvement in confusion. Laboratory investigations, particularly the markedly elevated anti-TPO titer, supported the diagnosis of SREAT syndrome. The subsequent management with an oral corticosteroid tapering regimen maintained the patient's clinical stability.ConclusionsThis case highlights the importance of considering autoimmune encephalopathy in patients with a history of autoimmune thyroiditis presenting with neurological and psychiatric symptoms. Further research is warranted to better understand the underlying pathomechanisms.

Long-Term Follow-up of Hypereosinophilic Syndrome Patients Treated with Mepolizumab: A Nationwide Real-Life Study of 59 Patients

Background Mepolizumab, a humanized monoclonal antibody directed against IL-5, has proven efficacious for the treatment of FIP1L1 ∷ PDGFRA ( F/P)-negative Hypereosinophilic Syndrome (HES) in two randomized controlled trials with short term follow-up. However, both its efficacy and safety profiles on the long term are unknown. Methods All F/P-negative HES patient treated with mepolizumab in France from 2003 to 2022 in either GlaxoSmithKline-sponsored randomized trials (MHE100185 and HES200622) or long-term access programs (MHE100901 and MHE10417) were included. For each study visit, we retrospectively collected the following data: drug doses (and spacing), HES-disease status, absolute eosinophil counts (AEC), and doses of oral corticosteroids (OCS). Clinical remission (CR) was defined as the absence of symptoms related to HES. Complete hematological remission (CHR) was defined as an AEC < 0.5 x 10 9/L, and relapse by the occurrence of new or worsening of HES-related symptoms, irrespective of either AEC or increase of HES treatments. Relapse-free survival was modeled using a Kaplan-Meier method. We also assessed the rates of “super responses”, a new outcome measure defined as the combination of both CR, CHR and complete withdrawal of OCS at last follow-up. Results and discussion Data were available for 64 out of the 80 patients identified. All patients ultimately received 300mg subcutaneous mepolizumab, but 27 (45.8%) patients had initially been started on higher doses (700 or 750 mg intravenous). Five patients were excluded because of misdiagnoses despite initially high AEC and HES-mimicking presentation (IgG4-related disease (n=1), Castleman's disease (n=1), lymphoma (n=2) and STAT6 gain-of-function mutation (n=1)). Ultimately, the study population consisted of 59 patients (idiopathic HES, n=51; lymphocytic HES, n=8) with chronic HES sensitive to high-dose OCS yet who remained OCS-dependent on the long run (median [IQR] dose of OCS at baseline: 11 [9-20] mg/d). In median, patients had two organs involved, with gastro-intestinal, respiratory, and cutaneous manifestations being the most frequent symptoms. After a median follow-up of 4.5 [2.5-12.3] years, 11 patients (19%) relapsed, among whom five were clearly related to prior mepolizumab spacing to more than four weeks between injections (Figure 1). In details, most of the patients were in CR (n=55, 93%) and/or in CHR (n=56, 95%) at last follow-up, including 38 (64%) OCS-free patients who fulfilled criteria for super response. No baseline predictive factor for super response was evidenced. When focusing on the 21 (36%) patients with more than eight years of follow-up (median 14.4 [12.2-17.3] years), outcomes tended to be the same as those of the overall population. At last follow-up more than 70% of patients were able to space mepolizumab's infusions for more than four weeks (median time between two injections at last follow-up: 8 [4-11] months). Ultimately, four patients were able to discontinue mepolizumab without subsequent relapse with more than two years of follow-up. There was no new safety signal, and no patient withdrew mepolizumab due to a treatment-related adverse event. Conclusion Mepolizumab remains highly efficacious in the long-term (including in patients with more than 10 years of follow-up), enabling sustained disease remission despite tapering of OCS and spacing of injections. Very few cases of mepolizumab failure were identified, among which the leading cause was HES misdiagnosis.

Efficacy and safety of deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, in patients with active systemic lupus erythematosus: Results from a phase 2, randomized, double-blind, placebo-controlled study

Introduction: Tyrosine kinase 2 (TYK2) mediates signaling of Type I interferons and IL-23, key cytokines involved in systemic lupus erythematosus (SLE) pathogenesis. Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for the treatment of adults with plaque psoriasis. This analysis assessed the efficacy and safety of deucravacitinib in patients with active SLE.
 Methods: This 48-week, double-blind, phase 2 trial (NCT03252587) randomized patients 1:1:1:1 to deucravacitinib (3 mg BID, 6 mg BID, 12 mg QD) or placebo. Oral corticosteroid tapering was required from weeks 8-20; further tapering was optional from weeks 32-40. The primary endpoint was the proportion of patients achieving SLE Responder Index-4 (SRI[4]) at week 32. Key secondary endpoints at week 48 included percentage of patients achieving SRI(4) and decrease of ≥50% from baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-50), in patients with baseline CLASI ≥10. Change from baseline in CLASI Activity Score (CLASI-A) over time was also assessed.
 Results: Of 363 randomized patients, 275 (76%) completed 48 weeks of treatment. Baseline demographic and disease characteristics were balanced across treatment groups, with baseline mean CLASI-A scores ranging from 8.0 to 8.6. The primary endpoint at week 32 was met, with significantly greater proportions of patients in deucravacitinib 3 mg BID and 6 mg BID groups vs placebo achieving SRI(4) responses (placebo: 34.4%; deucravacitinib 3 mg BID: 58.2%, P=0.0006; 6 mg BID: 49.5%, P=0.021; 12 mg QD: 44.9%, P=0.078). Patients treated with deucravacitinib demonstrated improvement across all secondary endpoints compared with placebo. In patients with CLASI ≥10 at baseline, greater mean changes from baseline in CLASI-A were observed in deucravacitinib vs placebo over 48 weeks of treatment (placebo: 16.7%; deucravacitinib 3 mg BID: 69.6%, P=0.0006; 6 mg BID: 56.0%, P=0.0058; 12 mg QD: 62.1%, P=0.0009). Rates of adverse events (AEs), serious AEs, and AEs of interest were similar between deucravacitinib and placebo groups. Most common AEs with deucravacitinib were upper respiratory tract infection, nasopharyngitis, headache, and urinary tract infection. No deaths, major adverse cardiac events, thrombotic events, systemic opportunistic infections, or active tuberculosis occurred.
 Conclusion: Deucravacitinib demonstrated sustained, meaningful clinical efficacy in SRI(4), improvement in mucocutaneous activity as measured by CLASI-A responses, and was well tolerated in patients with active SLE up to 48 weeks.

Treatment-Refractory Autoimmune Glial Fibrillary Acidic Protein Meningoencephalomyelitis in a Young Adult Female

Objective To describe a case of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy refractory to immunotherapy without evidence of malignancy or coexisting autoimmunity. Background Autoimmune GFAP astrocytopathy is an autoimmune disease of the central nervous system associated with the presence of GFAP-IgG in the CSF. Patients may present with acute or subacute onset of headache, encephalopathy, seizures, abnormal vision, weakness or numbness, postural tremor and cerebellar ataxia. GFAP astrocytopathy is usually corticocorticosteroid-responsive in the acute setting but may rarely require maintenance immunotherapy to prevent relapse. Treatment refractory cases should trigger work up for coexisting autoimmunity or malignancy. Design/Methods A 35-year-old female patient presented with subacute meningoencephalomyelitis with prodromal symptoms. Results Her cerebrospinal fluid revealed lymphocytic pleocytosis and elevated protein. Brain magnetic resonance imaging (MRI) with and without contrast showed perivascular radial enhancement and periventricular T2 FLAIR hyperintensity. Spinal MRI with and without contrast demonstrated longitudinal T2 FLAIR hyperintensity from T1-T2 to T7-T8. Despite high dose steroid treatment, her disease progressed with an enlarging periventricular lesion and worsening visual acuity. Biopsy of the enhancing periventricular lesion showed perivascular inflammation. After five cycles of plasma exchange along with a five-day course of intravenous methylprednisolone 1 gram daily, her symptoms stabilized. The CSF autoimmune encephalopathy panel (Mayo Clinic Laboratories) came back positive for GFAP-IgG antibody on tissue immunofluorescence assay, and was confirmed positive by GFAP cell-based assay. No neoplastic disease was identified using high resolution PET/CT scans. Based on the aggressiveness of her disease, she received one cycle of cyclophosphamide, and was discharged home on an oral corticosteroid taper. Even one year after addition of both mycophenolate mofetil and rituximab, MRI imaging continued to reveal new enhancing lesions. Conclusions Autoimmune GFAP astrocytopathy may sometimes require long-term immunosuppression even without presence of malignancy or other coexisting autoimmune disease.

TREATMENT OF DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS) WITH MEPOLIZUMAB

<h3>Introduction</h3> The standard treatment for DRESS involves stopping the culprit drug and often a prolonged course of systemic corticosteroids. Long-term systemic corticosteroids can have major adverse effects. We present a case of DRESS successfully managed with mepolizumab, an interleukin-5-antagonist, to decrease systemic corticosteroids. <h3>Case Description</h3> A 53-year-old male with a history of poorly controlled type 2 diabetes complicated by foot osteomyelitis was treated with vancomycin, ertapenem, and gabapentin. In three weeks, his absolute eosinophil count (AEC) increased to 1100/µL from a baseline of 300/µL. One week later he developed a diffuse morbilliform eruption, facial swelling, AEC of 2200/µL, and acute renal injury. He was diagnosed with DRESS. Vancomycin, ertapenem, and gabapentin were stopped, and he was treated with intravenous methylprednisolone. Vancomycin was presumed to be the likely culprit. By day 7 of hospitalization, his rash and creatinine improved and AEC decreased to 300/µL. He was discharged on oral prednisone 60mg and an adjusted insulin regimen due to elevated blood glucose. Two days post-discharge, his AEC increased to 3700/µL and he had persistent pruritus but improving rash. He was given mepolizumab 100mg and an oral corticosteroid taper. Within a week, AEC was zero. He was given a second dose of mepolizumab 100mg six weeks after the first dose as AEC increased to 900/µL. Three months post-discharge after a 7-week taper of steroids, he has not had recurrence of DRESS, AEC is ≤ 500/µL, and HbA1C remains within goal. <h3>Discussion</h3> Mepolizumab shows promise as a novel and safe steroid-sparing treatment for DRESS.

LB0004 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE, ALLOSTERIC TYK2 INHIBITOR, IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

LB0004 EFFICACY AND SAFETY OF DEUCRAVACITINIB, AN ORAL, SELECTIVE, ALLOSTERIC TYK2 INHIBITOR, IN PATIENTS WITH ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY

OCCUPATIONAL-HYPERSENSITIVITY PNEUMONITIS: A DIAGNOSIS NOT TO BE MISSED BY PROPER HISTORY TAKING

TOPIC: Occupational and Environmental Lung Diseases TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hypersensitivity Pneumonitis (HP) is an inflammatory and/or fibrotic disease affecting the lung parenchyma. Radiographic or histopathological findings help to categorize HP as either fibrotic (mixed inflammatory plus fibrotic or purely fibrotic) or non-fibrotic (purely inflammatory), being the primary determinant of prognosis. Rarely acute respiratory decline can be the first manifestation of chronic HP that may develop within a wide timeframe from weeks to years of exposure. CASE PRESENTATION: A 38-year-old male with no comorbidities or smoking history, presented with one week of progressive shortness of breath. Further questions revealed that since childhood he was working in a car painting shop without using protective equipment. Vital signs: Temperature 36.9, pulse 98 beats/min, respiratory rate 22 breaths/min, blood pressure 116/96 mmHg, and oxygen saturation 37% on room air, improved to 98% via a non-rebreather mask. He was not in respiratory distress. Findings included diffuse bilateral crackles over the lung fields. CXR showed diffuse patchy bilateral alveolar opacities. WBC count and serum procalcitonin were within normal limits. SARS-CoV-2 PCR performed was negative. Chest CT showed extensive diffuse bilateral lung consolidations, ground-glass opacities, honeycombing, and prominent mediastinal lymph nodes. Given the patient symptoms, high-risk exposure to isocyanate which exists in paints, radiologic findings, and by ruling out infectious etiologies, the suspected diagnosis of HP was made and treatment with IV Methylprednisone 60mg twice daily initiated. After 2 days, clinical status improved and oxygen requirements decreased to 8 LPM via Nasal Cannula. Bronchoscopy showed erythema throughout the tracheobronchial tree. Bronchoalveolar lavage (BAL) was performed and cytology showed: Reactive bronchial cells (24% Lymphocytes, 31% macrophages, 44% neutrophils). Consequently, a diagnosis of chronic, non-fibrotic HP was confirmed. Finally, after completing 7 days of IV steroid treatment, he was discharged home with 2 LPM supplemental oxygen. Instructions regarding oral corticosteroid tapering over a 3 week-period were provided. DISCUSSION: Diagnosis of chronic HP is predominantly based on exposure identification, CT scan pattern, and bronchoscopic/histopathological findings. BAL in the majority of the patients with non-fibrotic chronic HP shows elevated cell count with greater than 20% lymphocytes and this group responds to steroid therapy significantly. CONCLUSIONS: We would like to emphasize the high value of taking detailed patient history to detect causative agent exposure. Unprotected exposure to isocyanate was the key leading to further investigation including performing BAL in our patient. We also recommend health care providers educate their patients regarding proper safety equipment use, in case of occupational exposure to HP inducers. Prevention is always better than cure! REFERENCE #1: Raghu G, Remy-Jardin M, Ryerson CJ, Myers JL, Kreuter M, Vasakova M, et. al. Diagnosis of hypersensitivity pneumonitis in adults. An official ATS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care Med 2020; 202(3):e36–e69. REFERENCE #2: Koster MA, Thomson CC, Collins BF, Jenkins AR, Ruminjo JK and Raghu G. Diagnosis of hypersensitivity pneumonitis in adults, 2020 clinical practice guideline: summary for clinicians. Ann Am Thorac Soc 2020. DISCLOSURES: no disclosure on file for Manish Gugnani; No relevant relationships by Irina Gutierrez Puentes, source=Web Response No relevant relationships by Julio Piedra Butina, source=Web Response No relevant relationships by Asieh TakallooBakhtiari, source=Web Response

Expert Consensus on the Tapering of Oral Corticosteroids for the Treatment of Asthma. A Delphi Study.

Rationale: There is a need to minimize oral corticosteroid (OCS) use in patients with asthma to prevent their costly and burdensome adverse effects. Current guidelines do not provide recommendations for OCS tapering in patients with asthma.Objectives: To develop expert consensus on OCS tapering among international experts.Methods: A modified Delphi method was used to develop expert consensus statements relating to OCS use, tapering, adverse effects, adrenal insufficiency, and patient-physician shared decision-making. Initial statements proposed by experts were categorized, filtered for repetition, and presented back to experts over three ranking rounds to obtain consensus (≥70% agreement).Measurements and Main Results: One hundred thirty-one international experts participated in the study, and 296 statements were ranked. Numerous recommendations and guidance regarding appropriate OCS use were established. Experts agreed that OCS tapering should be attempted in all patients with asthma receiving maintenance OCS therapy, with personalization of tapering rhythm and speed. The importance of recognizing individual adverse effects was also established; however, a unified approach to the assessment of adrenal insufficiency was not reached. Shared decision-making was considered an important goal during the tapering process.Conclusions: In this Delphi study, expert consensus statements were generated on OCS use, tapering, adverse-effect screening, and shared decision-making, which may be used to inform clinical practice. Areas of nonconsensus were identified, highlighting uncertainty among the experts around some aspects of OCS use in asthma, such as adrenal insufficiency, which underscores the need for further research in these domains.

Recurrent Henoch-Sch\xf6nlein Purpura with bullous rash and pulmonary nodules

BackgroundHenoch-Schönlein purpura (HSP) is the most common vasculitis of childhood. It has a characteristic rash described as palpable purpura that most frequently affects the distal lower extremities and buttocks. HSP rarely presents with bullous rash nor pulmonary nodules.Case presentationWe present a novel case of a 12-years-old female with recurrent pediatric HSP with a combination of the rare manifestations of bullous rash and pulmonary nodules. She initially presented with the bullous rash, chest pain, cough, and abdominal pain. Patient was successfully treated with intravenous pulse corticosteroids followed by a high dose oral corticosteroid taper, with resolution of the bullous rash and pulmonary nodules.ConclusionThe rare manifestations of scarring bullous rash and pulmonary nodules can be presenting features of pediatric HSP, the combination of which has not been previously reported. The treatment of intravenous corticosteroid resolved patient’s abdominal symptoms, rash and pulmonary nodules.

A review of optic perineuritis

Optic perineuritis (OPN) refers to a spectrum of conditions involving pathologic inflammation of the optic nerve sheath. The classic triad of OPN consists of unilateral optic neuropathy associated with pain and/or disc oedema, but the condition often mimics other optic neuropathies, resulting in delayed diagnosis and suboptimal treatment. We performed a database search of Medline and Ovid in January 2016 for articles published in any language with the keywords ‘optic perineuritis’. Sixty articles were found, published from 1956 to 2015. Two reviewers (Tai ELM and Tevaraj JMP) performed an independent screening of abstracts. Articles of interest were subsequently examined. In this review, we highlight the salient features of OPN, with particular emphasis on the clinical differences between OPN and optic neuritis. Although the majority of cases of OPN are idiopathic, investigations are required to rule out specific infectious and inflammatory causes of secondary OPN. MRI is an invaluable component of the workup, as radiographic demonstration of peri-neural inflammation is diagnostic of OPN. Corticosteroid therapy results in dramatic and rapid reversal of the signs and symptoms, but prolonged therapy with slow tapering of oral corticosteroids may be necessary to reduce the risk of relapses.

ACR/ARP 2019

Anifrolumab, a human monoclonal antibody targeting the type I IFN receptor subunit 1, is beneficial for patients with moderate to severe systemic lupus erythematosus (SLE) who have active disease despite receiving standard therapy. Richard Furie (Northwell Health, USA) and Eric Morand (Monash University, Australia) presented findings from two phase 3 trials in SLE. In TULIP-1, patients were randomly assigned (2:1:2) to receive placebo (n=184), anifrolumab 150 mg (n=93), or anifrolumab 300 mg (n=180) intravenously every 4 weeks for 48 weeks. In TULIP-2, patients were randomly assigned (1:1) to receive either placebo (n=182) or anifrolumab 300 mg (n=180) on the same schedule. In both trials, standard-of-care treatment continued except for oral corticosteroid tapering for patients receiving 10 mg/day or more prednisone or equivalent at baseline. TULIP-1 did not meet its primary endpoint (SLE responder index-4 at week 52), with 65 (36%) of 180 patients in the 300 mg anifrolumab group achieving SRI-4 versus 74 (40%) of 184 in the placebo group. However, more patients in the anifrolumab group achieved a reduction in oral corticosteroid dose and a BILAG-based composite lupus assessment (BICLA) response, suggesting potential clinical benefit of the drug. In TULIP-2, anifrolumab was superior to placebo for BICLA response at week 52 (the primary endpoint), with 86 (48%) of 180 patients in the anifrolumab group and 57 (31%) of 182 in the placebo group achieving BICLA response. The safety profile of anifrolumab's safety was similar to that observed in phase 2 trials. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trialThe primary endpoint was not reached. However, several secondary endpoints, including reduction in oral corticosteroid dose, CLASI responses, and BICLA responses, suggest clinical benefit of anifrolumab compared with placebo. Conclusive evidence for the efficacy of anifrolumab awaits further phase 3 trial data. Despite the inherent limitations of a 1-year phase 3 study, such as incomplete knowledge of applicability to the general population and scarce detection of rare safety signals, in addition to complications from prespecified restricted medication rules, our results suggest that anifrolumab might have the potential to provide a treatment option for patients who have active SLE while receiving standard therapy. Full-Text PDF

Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial

Summary Background Type I interferons are involved in systemic lupus erythematosus (SLE) pathogenesis. In a phase 2 trial, anifrolumab, a human monoclonal antibody to type I interferon receptor subunit 1, suppressed interferon gene signatures and substantially reduced SLE disease activity. Here, we sought to confirm the efficacy of anifrolumab versus placebo in a phase 3 trial of adult patients with SLE and moderate-to-severe disease activity despite standard-of-care treatment. Methods TULIP-1 was a double-blind, randomised, controlled, phase 3 trial done at 123 sites in 18 countries. Included patients were aged 18–70 years, with moderate-to-severe SLE, and ongoing stable treatment with either prednisone or equivalent, an antimalarial, azathioprine, mizoribine, mycophenolate mofetil or mycophenolic acid, or methotrexate. Patients were randomly assigned (2:1:2) to receive placebo, anifrolumab 150 mg, or anifrolumab 300 mg intravenously every 4 weeks for 48 weeks. Stable standard-of-care treatment continued except for mandatory attempts at oral corticosteroid tapering for patients receiving prednisone or equivalent of 10 mg/day or more at baseline. The primary outcome was the difference between the proportion of patients who achieved an SLE responder index-4 (SRI-4) response at week 52 with anifrolumab 300 mg versus with placebo. Key secondary outcomes were the difference between the anifrolumab 300 mg group and the placebo group in: proportion of patients in the interferon gene signature test—high subgroup who achieved SRI-4 at week 52; proportion of patients on 10 mg/day or more corticosteroids at baseline who achieved a sustained dose reduction to 7·5 mg/day or less from week 40 to 52; proportion of patients with a cutaneous lupus erythematosus disease area and severity index (CLASI) activity score of 10 or higher at baseline who achieved a 50% or more reduction in CLASI score by week 12; proportion of patients who achieved SRI-4 at week 24; and annualised flare rate through week 52. Other measures of disease activity were also assessed at week 52, including the British Isles Lupus Assessment Group-based composite lupus assessment (BICLA). Safety was also assessed. Efficacy and safety analyses were done in the population of patients who received at least one dose of study drug. This trial was registered at ClinicalTrials.gov (NCT02446912). Findings Between June 9, 2015, and June 16, 2017, 457 patients were randomly assigned to the anifrolumab 300 mg group (n=180), the anifrolumab 150 mg group (n=93), or the placebo group (n=184). The proportion of patients at week 52 with an SRI-4 response was similar between anifrolumab 300 mg (65 [36%] of 180) and placebo (74 [40%] of 184; difference −4·2 [95% CI −14·2 to 5·8], p=0·41). Similarly, proportions of patients with an SRI-4 response at week 24, and at week 52 in patients in the interferon gene signature test—high subgroup, did not differ between the anifrolumab and placebo groups. In patients with baseline oral corticosteroids of at least 10 mg/day, sustained dose reduction to 7·5 mg/day or less was achieved by 42 (41%) of 103 patients in the anifrolumab 300 mg group and 33 (32%) of 102 patients in the placebo group (difference 8·9 [95% CI −4·1 to 21·9]). In patients with CLASI activity score of at least 10 at baseline, at least 50% reduction by week 12 was achieved by 24 (42%) of 58 patients in the anifrolumab 300 mg group and 14 (25%) of 54 in the placebo group (difference 17·0 [95% CI −0·3 to 34·3]). Annualised flare rates were 0·60 for anifrolumab and 0·72 for placebo (rate ratio 0·83 [95% CI 0·60 to 1·14]). BICLA response was achieved by 67 (37%) of 180 patients receiving anifrolumab 300 mg versus 49 (27%) of 184 receiving placebo (difference 10·1 [95% CI 0·6 to 19·7]). Anifrolumab's safety profile was similar to that observed in phase 2, with similar proportions of patients having a serious adverse event between groups (25 [14%] of 180 for anifrolumab 300 mg, ten [11%] of 93 for anifrolumab 150 mg, and 30 [16%] of 184 for placebo). Interpretation The primary endpoint was not reached. However, several secondary endpoints, including reduction in oral corticosteroid dose, CLASI responses, and BICLA responses, suggest clinical benefit of anifrolumab compared with placebo. Conclusive evidence for the efficacy of anifrolumab awaits further phase 3 trial data. Despite the inherent limitations of a 1-year phase 3 study, such as incomplete knowledge of applicability to the general population and scarce detection of rare safety signals, in addition to complications from prespecified restricted medication rules, our results suggest that anifrolumab might have the potential to provide a treatment option for patients who have active SLE while receiving standard therapy. Funding AstraZeneca.

Predictors of efficacy for combination oral and topical corticosteroids to treat patients with chronic rhinosinusitis with nasal polyps.

A short-course oral corticosteroid taper and topical intranasal corticosteroids may be used to maximize the success of medical management for chronic rhinosinusitis with nasal polyps (CRSwNP). In this study, we sought to identify characteristics that would be predictive of efficacy for this combination regimen. Sixty-four patients with CRS, bilateral polyps, a polyp score of at least 3, and a 22-item Sino-Nasal Outcome Test (SNOT-22) score ≥20 were prospectively enrolled and uniformly treated with a 15-day prednisone taper and twice daily dilute budesonide irrigations. Participants were assessed at enrollment and at follow up, 2 to 5 months later. Clinical and demographic characteristics were assessed at enrollment. At both time points, CRS symptoms were assessed with SNOT-22, and polyp score (range, 0 to 6) was assessed endoscopically. Associations were determined with regression. Pretreatment SNOT-22 score (adjusted β = -0.83; 95% CI, -1.08 to -0.58; p < 0.001) and comorbid asthma (adjusted β = 15.75; 95% CI, 4.74 to 26.75; p = 0.007) were associated with a change in SNOT-22 experienced over the study period. Achieving a greater-than-1 minimal clinically important difference (MCID) improvement in SNOT-22 score was also associated with pretreatment SNOT-22 score (adjusted OR = 1.09; 95% CI, 1.04 to 1.14; p < 0.001) and comorbid asthma (adjusted OR = 0.13; 95% CI, 0.03 to 0.72; p = 0.019). SNOT-22 score ≥47 had 81.5% sensitivity and 78.4% specificity to detect patients experiencing 1 MCID improvement. Pretreatment polyp score was not associated with any outcome metric. In treatment of CRSwNP with prednisone and budesonide irrigations, pretreatment endoscopy was not informative of treatment response. Pretreatment SNOT-22 and comorbid asthma may be more predictive.

Oral Corticosteroid Use for the Treatment of Chronic Eosinophilic Disease: A Patient's and His Physician's Experience.

This article, coauthored by a patient with eosinophilic granulomatosis with polyangiitis (EGPA) initially presenting as severe eosinophilic asthma and his physician-specialist, discusses the use and management of oral corticosteroid (OCS) treatment. It also considers the importance of early diagnosis of a rare disease and patient education. The patient describes his journey from progressive worsening of asthma and eventual diagnosis of EGPA to long-term OCS treatment and then participation in a clinical trial for this rare disease, involving the introduction of targeted biologic therapy with OCS tapering. The physician describes the importance of patient referral to obtain a correct diagnosis and optimal maintenance treatment, the balance between risk of adverse events associated with long-term OCS use and benefits of disease control, and various aspects of patient participation in clinical trials. Finally, the patient describes the role of continual patient education in the management of disease and OCS treatment. These considerations can apply to all chronic inflammatory diseases requiring maintenance OCS treatment.Funding: AstraZeneca.

A case of probable Vogt\u2013Koyanagi\u2013Harada disease in a 3-year-old girl

BackgroundVogt–Koyanagi–Harada (VKH) disease is a T-cell-mediated autoimmune disorder characterized by bilateral granulomatous panuveitis with various systemic manifestations. Although VKH disease rarely occurs in the pediatric population, the clinical course tends to be aggressive, and the visual prognosis is worse than that in adult patients due to severe ocular complications secondary to recurrent inflammation.Case presentationA 3-year-old girl with probable VKH was referred to Kobe University Hospital. She had severe bilateral panuveitis with posterior synechiae of the iris, marked optic disk swelling, and serous retinal detachment in both eyes, and her best corrected visual acuities (BCVAs) were 20/200 OD and 20/125 OS. A third course of therapy was administered because serous retinal detachment remained after two courses of therapy. She was treated with three courses of high-dose intravenous corticosteroid therapy, followed by slow tapering of oral corticosteroids. Her BCVAs recovered to 20/16 OU, and relapse of ocular inflammation and side effect of treatment were not observed during the 1.5-year follow-up period.ConclusionsWe experienced a pediatric patient with probable VKH disease who was treated with three courses of high-dose intravenous corticosteroid therapy. With the favorable clinical course in our patient, initial treatment with repeated high-dose intravenous corticosteroid therapy might be beneficial in pediatric VKH disease.

Expert Statements Concerning the Tapering of Oral Corticosteroids (OCS) for the Treatment of Asthma

Expert Statements Concerning the Tapering of Oral Corticosteroids (OCS) for the Treatment of Asthma

Expert Statements Concerning the Tapering of Oral Corticosteroids (OCS) for the Treatment of Asthma

Expert Statements Concerning the Tapering of Oral Corticosteroids (OCS) for the Treatment of Asthma

PERIPHERAL RETINAL VASCULITIS: Analysis of 110 Consecutive Cases and a Contemporary Reappraisal of Tubercular Etiology.

Describe the clinical features and outcomes of patients with peripheral retinal vasculitis (RV) and describe clinical characteristics of presumed tubercular RV in a nonendemic setting. Retrospective cohort study of 110 consecutive patients with peripheral RV at a tertiary referral eye care center in the United Kingdom. Retinal vasculitis was defined as RV with vitritis associated with peripheral retinal ischemia. Patients who also had positive Quantiferon Gold in Tube test, positive tuberculin skin test, and/or other evidence of systemic tuberculosis such as biopsy were labeled with presumed tubercular RV. Treatment success was defined as resolution of inflammation, and successful tapering of oral corticosteroids to less than 10 mg/day or topical steroids to less than twice a day. Mean age of the study population was 42.69 ± 14.95 years. Patients were predominantly Asian (49.1%) and Male (67.0%). A total of 73.2% had bilateral involvement. Sixty-nine (62.72%) patients had presumed tubercular RV. A total of 52.8% patients received antitubercular therapy, 65.5% received oral corticosteroids, and 17.3% required steroid-sparing oral immunosuppressive agents. A total of 85.19% of patients with presumed tubercular RV achieved treatment success with concurrent antitubercular therapy as against 75.61% of patients with nontubercular RV. This is the largest study of the epidemiology, clinical features, and outcomes of both peripheral RV and presumed tubercular RV to date. Presumed tubercular RV commonly seems to affect young males of Asian descent and had vitreous hemorrhage as common clinical findings and also demonstrated a good treatment outcome with antitubercular therapy.

Oral corticosteroid prescribing habits of Canadian Otolaryngologist-Head and Neck Surgeons.

BackgroundOral corticosteroids (OCSs) are widely prescribed in Otolaryngology-Head & Neck surgery (OtoHNS). There is evidence in the literature regarding specific dosing regimens. However, it is not known to what extent these recommendations are being implemented in practice.MethodsAn anonymous online survey was sent to Canadian Society of Otolaryngology-Head and Neck Surgery members (N = 696). Dosing, frequency and tapering of OCSs were assessed in acute rhino-sinusitis (ARS), chronic rhino-sinusitis with (CRSwP) and without polyps (CRSsP), sudden sensori-neural hearing loss (SSNHL), and idiopathic facial nerve/Bell’s palsy (IFN). Participants were asked to complete for conditions treated and results were compared with current guidelines. Development of prescribing habits and observed complications were also explored.Results124 surveys (18 %) were completed. In CRSwP (N = 98), the median dose was 50 mg (Range: 10–100 mg) and the average duration was 8 days (Range: 1–21 days). In CRSsP (N = 29), the median dose was 50 mg (Range: 20-80 mg) and the average duration was 8 days (Range: 1–14 days). In SSNHL (N = 118), the median dose was 60 mg (Range: 10–120 mg) and the average duration was 10 days (Range: 1–21 days). In IFN (N = 108), the median dose was 50 mg (Range: 10–100 mg) and the average duration was 10 days (Range: 1–21 days). Tapering dosages were used in treating CRSwP (64 %), CRSsP (62 %), ARS (44 %), SSNHL (60 %) and IFN (53 %). Respondents most frequently perceived “Mentor/Preceptor Guidance” as a source of their prescribing habits.ConclusionThere is significant heterogeneity in OCS prescribing habits despite the availability of fairly consistent evidence in the literature for some of the surveyed conditions. Improvements in standardization should be made with the aim of enhancing outcomes and reducing complications.

Impact of Perioperative Oral Steroid Use on Low-frequency Hearing Preservation After Cochlear Implantation.

To investigate the efficacy of a perioperative oral steroid taper on low-frequency hearing preservation after cochlear implantation. Retrospective case series. Tertiary referral center. Consecutive cochlear implant recipients between January 2012 and December 2014 who were candidates for a hearing preservation approach based on preoperative pure tone thresholds were identified. A subgroup of patients received a 2-week oral corticosteroid taper beginning 3 days before surgery. All patients were implanted using standard length electrodes. The preservation of low-frequency pure tone thresholds on the first postoperative audiogram was assessed. Secondary outcome measures included the respective impacts of age, diabetes, and electrode array type on hearing preservation, the durability of hearing preservation over time, and the development of medical complications related to steroid use. Twenty-seven ears met inclusion criterion, and the mean age at implantation was 49.8 years (median 62 yr, range 2-81 yr). Twenty patients (74.1%, mean age 48.7 yr) received an oral corticosteroid taper, whereas 7 (25.9%, mean age 53.1 yr) did not. The rate (p < 0.01) and degree (p < 0.01) of hearing preservation as measured at implant activation was greater for patients who received an oral steroid taper than those who did not. There were no medical complications related to steroid use. A 2-week oral prednisone taper beginning before surgery may positively affect the incidence and degree of low-frequency hearing preservation after cochlear implantation.