Low-dose Oral Steroids Research Articles

Comparison between Tab Tofacitinib and Low-Dose Oral Steroid in Patients Having Vitiligo Over 6 Months

Background: Vitiligo is a chronic autoimmune condition characterized by depigmented patches on the skin, presenting significant treatment challenges. Recent studies have focused on the immunomodulatory effects of tofacitinib, a Janus kinase inhibitor, and the anti-inflammatory properties of low-dose oral steroids, yet comparative data on their efficacy and safety are scarce. Objective: The aim of this study was to compare the efficacy and safety of tofacitinib tablets with low-dose oral steroids in the treatment of vitiligo over a six-month period. Methods: This descriptive comparative study involved 42 patients with vitiligo, recruited from the Department of Dermatology at the Combined Military Hospital Abbottabad between November 15, 2022, and November 15, 2023. Participants were randomly assigned to receive either tofacitinib tablets (Group A) or low-dose oral steroids (Group B), with adherence monitored through routine follow-ups. The primary outcome measured was the proportion of repigmentation, assessed using standardized photography and Image software, alongside lesion size reduction and the incidence of adverse events. Statistical analyses were performed using SPSS version 25, with p-values ≤0.05 considered significant. Results: Both groups demonstrated comparable efficacy in terms of repigmentation and lesion size reduction, with no significant difference observed between the tofacitinib (55.8% ± 15.2 repigmentation; 100% lesion size reduction) and low-dose steroid groups (50.2% ± 13.5 repigmentation; 85.71% lesion size reduction) at the 6-month follow-up. The incidence of adverse events was similarly low and statistically non-significant between the two groups. Conclusion: Tofacitinib and low-dose oral steroids are both effective and safe for the treatment of vitiligo, offering valuable options for patient management. Further research with larger sample sizes and longer follow-up is necessary to confirm these findings and evaluate the long-term outcomes of these treatments.

Steroid-responsive Multifocal Motor Neuropathy with Cranial Manifestations

The typical presentation of multifocal motor neuropathy (MMN) is progressive asymmetric limb weakness. Cranial neuropathy is rare. We report a 28-year-old woman with cranial and bulbar palsies but with typical electrophysiological features of MMN by multifocal motor conduction blocks and serological markers of anti-ganglioside GM1 antibodies. The previous consensus on the treatment of MMN is intravenous immunoglobulins, but our patient responded to oral steroids and had clinical and electrophysiological improvement under continuous low-dose prednisolone treatment. In summary, MMN is a treatable chronic inflammatory disease of peripheral nerves. Cranial neuropathies can be its initial presentation. Electromyography studies are crucial for MMN diagnosis and helpful in monitoring disease activity and treatment responses. Although the previous guideline did not suggest using steroids for MMN, with careful patient selection, low-dose oral steroids can be an effective treatment in patients with relatively minor symptoms.

Non-biologic, steroid-sparing therapies for non-infectious intermediate, posterior, and panuveitis in adults.

Non-biologic, steroid-sparing therapies for non-infectious intermediate, posterior, and panuveitis in adults.

Dupilumab combined with low-dose systemic steroid therapy improves efficacy and safety for bullous pemphigoid.

Routine systemic therapy for bullous pemphigoid (BP) has been challenged due to the inevitably adverse effects. According to the successful applications of dupilumab in BP cases reported, therefore, we investigate the real-life efficacy and safety of dupilumab combined with low-dose oral steroid for BP. A cohort of BP patients who received either dupilumab plus low-dose methylprednisolone (dupilumab group) or merely methylprednisolone (control group) was retrospectively reviewed. The time to disease control was investigated. Additionally, the control dose and cumulative dosage of steroids, Bullous Pemphigoid Disease Area Index (BPDAI) scores, pruritus scores, and adverse events were assessed. A total of 40 patients, with 20 in each group, were retrospectively studied. The time to disease control was shorter in the dupilumab group than the control group (14 days vs. 19 days, p=0.043). When the disease was controlled, the control dose and cumulative dosage of methylprednisolone in the dupilumab group were substantially lower than those of the control (24.6mg vs. 48.8 mg, 376.8mg vs. 985.6 mg, both p < 0.01). Compared with the control, the percentage change from baseline in BPDAI scores and pruritus scores were both significantly reduced, and the adverse events were also less frequent in the dupilumab group. The combination therapy of dupilumab plus low-dose methylprednisolone exhibits superior efficacy and safety in comparison with the current first-line systemic therapy for BP.

FC054: Voclosporin for Lupus Nephritis: Results of the Two-Year Aurora 2 Continuation Study

Abstract BACKGROUND AND AIMS Voclosporin, a novel calcineurin inhibitor, was approved in the USA in January 2021 for the treatment of adult patients with active lupus nephritis in combination with background immunosuppressive therapy. Voclosporin has a favorable metabolic profile and a consistent dose-concentration relationship, eliminating the need for therapeutic drug monitoring. Previously reported results from the Phase 2 AURA-LV and Phase 3 AURORA 1 studies showed that the addition of voclosporin to mycophenolate mofetil (MMF) and low-dose steroids in patients with lupus nephritis significantly increased rates of complete renal response at 48 weeks (AURA-LV) and 52 weeks (AURORA 1). Here we report the results of the completed continuation study, AURORA 2, which assessed the long-term safety and tolerability of voclosporin compared with placebo in patients with lupus nephritis receiving treatment for an additional 24 months following completion of the AURORA 1 study. METHOD Key inclusion criteria for the parent AURORA 1 study included a diagnosis of biopsy-proven active lupus nephritis (Class III, IV, or V ± III/IV), proteinuria ≥ 1.5 mg/mg (≥2 mg/mg for Class V) and estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m2. Patients who completed AURORA 1 were eligible to enroll in AURORA 2 and continued with the same blinded treatment of voclosporin (23.7 mg BID) or placebo in combination with MMF (target dose 2 g/day) and low-dose oral steroids. Safety and tolerability were evaluated by monitoring adverse events and laboratory assessments including eGFR; changes in urine protein creatinine ratio (UPCR) were also assessed. RESULTS In total, 116 patients in the voclosporin arm and 100 patients in the control arm enrolled in AURORA 2, with 92 (79.3%) and 73 (73.0%) patients in each respective arm completing treatment to the end of AURORA 2. There were no new or unexpected safety signals detected in patients who continued on treatment with voclosporin compared to control-treated patients. Rates of serious adverse events in the voclosporin (19.0%) and control arms (24.0%) were similar, with eight serious adverse events of infection in each arm. Estimated glomerular filtration rate remained stable through the end of AURORA 2 (Figure 1). The slopes of the least-squares (LS) mean change in corrected eGFR from AURORA 2 baseline to end of study were –0.2 [95% confidence interval (CI) –3.0 to 2.7' in the voclosporin arm and –5.4 (95% CI –8.4 to –2.3) in the control arm. There were no deaths in the voclosporin arm during AURORA 2; four deaths were reported in the control arm due to pulmonary embolism (n = 1) and coronavirus infection (n = 3). The LS mean reductions in UPCR observed in AURORA 1 were maintained in AURORA 2 with no increase in UPCR noted at the follow-up visit 4 weeks after study drug discontinuation (Figure 2). CONCLUSION Voclosporin was well-tolerated over three years of treatment with a similar safety profile to control and no unexpected safety signals detected. Further, the significant and meaningful reductions in proteinuria initially achieved in AURORA 1 were maintained throughout AURORA 2. These data provide evidence of a long-term treatment benefit of voclosporin in patients with lupus nephritis.

Profuse haematochezia related to Crohn’s disease: a rare case report

Background: Lower gastrointestinal bleeding (LGIB) can be caused by irritable bowel disease. Haematochezia is one of the LGIB symptoms. Profuse haematochezia is a rare complication in Crohn’s disease. Case Presentation: We reported a 24-year-old patient with profuse haematochezia with severe anaemia and hypovolemic shock. Anamnesis, physical examination and colonoscopy showed that haematochezia was caused by Crohn’s disease. Colonoscopy was done after the patient was hemodynamically stable with findings of external haemorrhoid and multiple ulcers with varying size (0.5–2 cm) on ascending colon, caecum and terminal ileum. The tissue histopathology of ileocecal junction indicated intestinal epithelia with partially eroded, crypts infiltrated by inflammatory cells, swollen lamina propria with proliferation and dilation of blood vessels indicting the Crohn’s disease. The patient then treated with Crohn’s disease medical therapy including low dose oral steroid, sulfasalazine and antibiotics. Clinical improvement was found on one week follow-up after discharge from hospital. Conclusion: Profuse haematochezia could be associated with Crohn’s disease and the comprehensive approaches should be taken to manage the Crohn’s disease with such presentation.

POS-390 ELECTROLYTE PROFILES OF LUPUS NEPHRITIS PATIENTS TREATED WITH THE NOVEL CALCINEURIN INHIBITOR VOCLOSPORIN

Electrolyte imbalances, which can be modulated within the kidney, have been previously reported with calcineurin inhibitor (CNI) utilization in solid organ transplant.1,2Dietary supplementation of electrolytes may correct serum electrolyte imbalances; therefore, it can be useful to evaluate urinary excretion over time to detect changes in electrolytes due to diet or to confirm clinical findings in serum. Voclosporin is a novel CNI approved in the US for the treatment of adult patients with active lupus nephritis in combination with background immunosuppressive therapy. Data from the pivotal Phase 3 AURORA 1 study showed that the addition of voclosporin to mycophenolate mofetil (MMF) and low-dose steroids results in higher complete renal response rates at one year (40.8% vs 22.5%; OR 2.65; p<0.0001) in patients with lupus nephritis. AURORA 1 was a double-blind, randomized controlled trial designed to evaluate oral voclosporin (23.7 mg twice daily) compared to placebo in patients with active lupus nephritis, with all patients receiving MMF (target dose 1 g twice daily) and low-dose oral steroids (rapidly tapered to 2.5 mg daily at week 16). Serum electrolyte imbalances including hypomagnesemia are common adverse events associated with CNIs. In contrast to these reports, mean serum electrolyte concentrations of patients treated with voclosporin were within normal ranges in AURORA 1. As serum electrolytes concentrations can be impacted by dietary supplementation, we evaluated urinary excretion rates to assess if inadvertent dietary supplementation during the study had impacted the findings in serum. Twenty-four-hour urine samples from 60 patients in each treatment arm were selected including patients that responded to treatment at one year with at least 50% reduction in urine protein creatinine ratio (UPCR) from baseline (treatment responders), those who had not (non-responders), and patients who had at least 30% reduction from baseline in estimated glomerular filtration rate (eGFR) during the study. Mean change from baseline to one year in magnesium, potassium and sodium are presented as 24-hour urinary electrolyte excretion rates. Mean changes from baseline in urinary electrolyte excretion were small for magnesium (≤13.4 mg/24 hours) and potassium (≤6.4 mmol/24 hours) with no significant differences between treatment arms for any of the subgroups. Sodium excretion decreased from baseline in all subgroups (≤30.5 mmol/24 hours) except for responders in the control arm (increase of 14.0 mmol/24 hours) at one year (Table 1). Patients with lupus nephritis in AURORA 1 treated with voclosporin in combination with MMF and low-dose steroids achieved significantly higher complete renal response rates compared to patients treated with only MMF and low-dose steroids. At the doses studied, changes from baseline in urinary electrolyte excretion of magnesium, potassium, and sodium were not clinically meaningful in either treatment arm regardless of response to treatment. These results confirmed dietary supplementation did not impact the findings in serum concentrations. Together with the reported normal electrolyte concentrations in serum, this study confirms voclosporin has no meaningful impact on mean concentrations of electrolytes. This analysis further supports the safety and efficacy of voclosporin for the treatment of patients with lupus nephritis.

A Long-Term follow-up Study of Lupus Nephritis in a Single Tertiary Care Centre.

Lupus nephritis (LN) is an immune complex glomerulonephritis, which is a very serious complication of systemic lupus erythematosus (SLE) as it can progress to end-stage kidney disease (ESKD). In this study of 92 renal biopsy-proven LN, the patients were followed up for a minimum period of 2 years with a mean follow-up period of 5.4 ± 3.4 years. The mean serum creatinine of our study population was 1.4 ± 1.53. Our study population included 2 patients with class I lesions, 5 with class II, 22 with Class III, 53 with Class IV, and 10 with Class V lesions. Our therapeutic approach included only oral steroids for class I and class II lesions; for class III, IV, and V lesions, our approach included pulse steroids followed by oral steroids with either intravenous (IV) monthly cyclophosphamide (CYC) or mycophenolate mofetil (MMF). For maintenance, azathioprine or MMF were used along with low-dose oral steroids after 6 months of CYC or MMF. In CYC induction group containing 78 patients (84.7%), 66 patients (84.6%) attained remission (CR + PR), relapse in five patients (6.4%), ESRD on HD in five patients (6.4%), and death in two patients (2.6%). At the end of the study, in all groups, 79 patients (85.86%) were in remission (CR + PR), six patients (6.5%) were in relapse, five patients (5.4%) had reached the ESKD stage on HD, and two patients (2.2%) died.

P.087 Successful response to rituximab in a patient with Aβ related angiitis

Background: Aβ-related angiitis (AβRA) is a rare presentation of cerebral amyloid angiopathy, where vasculitis results from an auto-immune reaction to amyloid deposits in leptomeningeal and cortical vessel walls. Anti-CD20 monoclonal antibodies, such as rituximab, have demonstrated efficacy in systemic small vessel vasculitides, particularly in refractory cases. The efficacy of rituximab in AβRA remains unknown. Methods: Patient chart, functional measures, and laboratory findings were reviewed from the time of patient admission until 12 months after discharge. Results: A 61-year-old man presented with headache and altered mental status. Brain MRI revealed multiple cortical infarcts, leptomeningeal enhancement, and cortical microbleeds, and brain biopsy ultimately confirmed the diagnosis of AβRA. The patient developed new ischemic lesions despite corticosteroid pulse, and intravenous cyclophosphamide was halted after four weeks due to iatrogenic acute hepatitis. Rituximab was initiated and led to sustained clinical improvement with no subsequent relapses. Maintenance therapy involved gradually tapered low-dose oral steroids and rituximab at 6- and 12-months post-induction. Conclusions: This report suggests that rituximab may be effective in inducing remission and preventing relapses in biopsy-proven case of AβRA. Controlled studies are needed to better assess the efficacy and tolerability of anti-CD20 antibodies in cerebral vasculitis.

Journal Club: Efficacy and Safety of Voclosporin Versus Placebo for Lupus Nephritis (AURORA 1): A Double-Blind, Randomized, Multicenter, Placebo-Controlled, Phase 3 Trial.

ObjectiveVoclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis (LN), improved complete renal response rates in patients with LN in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of LN.MethodsThis multicenter, double‐blind, randomized phase 3 trial was done in 142 hospitals and clinics across 27 countries. Patients with a diagnosis of systemic lupus erythematosus and LN, according to the American College of Rheumatology criteria, who had undergone a kidney biopsy within 2 years that showed class III, IV, or V (alone or in combination with class III or IV) were eligible for this study. Patients were randomly assigned (1:1) to receive oral voclosporin (23.7 mg twice daily) or a placebo, on a background of mycophenolate mofetil (1 g twice daily) and rapidly tapered low‐dose oral steroids, by use of an interactive web response system. The primary endpoint was complete renal response at 52 weeks, defined as a composite of urine protein creatinine ratio of 0.5 mg/mg or less, stable renal function (defined as estimated glomerular filtration rate [eGFR] ≥60 ml/min/1.73m2 or no confirmed decrease from baseline in eGFR of > 20%), no administration of rescue medication, and no more than 10 mg prednisone equivalent per day for 3 or more consecutive days or 7 or more days during Week 44 through Week 52 (just before the primary endpoint assessment). Safety was also assessed. Efficacy analysis was by intention to treat, and safety analysis was by randomized patients receiving at least one dose of study treatment.ResultsBetween April 13, 2017, and October 10, 2019, 179 patients were assigned to the voclosporin group and 178 were assigned to the placebo group. The primary endpoint of complete renal response at Week 52 was achieved in significantly more patients in the voclosporin group than in the placebo group (73 [41%] of 179 patients vs 40 [23%] of 178 patients; odds ratio, 2.65; 95% confidence interval [CI] 1.64‐4.27; P < 0·0001). The adverse event profile was balanced between the two groups; serious adverse events occurred in 37 (21%) of 178 patients in the voclosporin group and 38 (21%) of 178 patients in the placebo group. The most frequent serious adverse event involving infection was pneumonia, occurring in seven (4%) patients in the voclosporin group and in eight (4%) patients in the placebo group. A total of six patients died during the study or study follow‐up period (one [<1%] patient in the voclosporin group and five [3%] patients in the placebo group). None of the events leading to death were considered by the investigators to be related to the study treatments.ConclusionVoclosporin in combination with mycophenolate mofetil (MMF) and low‐dose steroids led to a clinically and statistically superior complete renal response rate versus MMF and low‐dose steroids alone, with a comparable safety profile. This finding is an important advancement in the treatment of patients with active LN.

Posterior reversible encephalopathy syndrome (PRES) presenting as Status Epilepticus in a case of Autoimmune Hemolytic Anemia (AIHA): A Case report

Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic state, caused by imbalance in autoregulation of posterior cerebral circulation. We report a case of young female, presented at emergency department with complains of nausea, vomiting and generalized tonic clonic seizures prior to admission. During the course of hospital stay patient landed in status epilepticus which was treated appropriately. Patient’s magnetic resonance imaging (MRI) was done which had classical features of vasogenic edema in occipital and parietal region, suggestive of PRES. She was a known case of autoimmune hemolytic anemia thatwas treated with multiple blood transfusions and low dose oral steroids. She was discharged after complete resolution of symptoms with the advice to follow up in medicine outpatient department. Our case describes about autoimmune hemolytic anemia in which occurrence of PRES is uncommon. Early diagnosis and robust treatment can prevent permanent damage to the brain, and is often associated with complete recovery.

Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial

Voclosporin, a novel calcineurin inhibitor approved for the treatment of adults with lupus nephritis, improved complete renal response rates in patients with lupus nephritis in a phase 2 trial. This study aimed to evaluate the efficacy and safety of voclosporin for the treatment of lupus nephritis. This multicentre, double-blind, randomised phase 3 trial was done in 142 hospitals and clinics across 27 countries. Patients with a diagnosis of systemic lupus erythematosus with lupus nephritis according to the American College of Rheumatology criteria, and a kidney biopsy within 2 years that showed class III, IV, or V (alone or in combination with class III or IV) were eligible. Patients were randomly assigned (1:1) to oral voclosporin (23·7 mg twice daily) or placebo, on a background of mycophenolate mofetil (1 g twice daily) and rapidly tapered low-dose oral steroids, by use of an interactive web response system. The primary endpoint was complete renal response at 52 weeks defined as a composite of urine protein creatinine ratio of 0·5 mg/mg or less, stable renal function (defined as estimated glomerular filtration rate [eGFR] ≥60 mL/min/1·73 m2 or no confirmed decrease from baseline in eGFR of >20%), no administration of rescue medication, and no more than 10 mg prednisone equivalent per day for 3 or more consecutive days or for 7 or more days during weeks 44 through 52, just before the primary endpoint assessment. Safety was also assessed. Efficacy analysis was by intention-to-treat and safety analysis by randomised patients receiving at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, NCT03021499. Between April 13, 2017, and Oct 10, 2019, 179 patients were assigned to the voclosporin group and 178 to the placebo group. The primary endpoint of complete renal response at week 52 was achieved in significantly more patients in the voclosporin group than in the placebo group (73 [41%] of 179 patients vs 40 [23%] of 178 patients; odds ratio 2·65; 95% CI 1·64-4·27; p<0·0001). The adverse event profile was balanced between the two groups; serious adverse events occurred in 37 (21%) of 178 in the voclosporin group and 38 (21%) of 178 patients in the placebo group. The most frequent serious adverse event involving infection was pneumonia, occurring in 7 (4%) patients in the voclosporin group and in 8 (4%) patients in the placebo group. A total of six patients died during the study or study follow-up period (one [<1%] patient in the voclosporin group and five [3%] patients in the placebo group). None of the events leading to death were considered by the investigators to be related to the study treatments. Voclosporin in combination with MMF and low-dose steroids led to a clinically and statistically superior complete renal response rate versus MMF and low-dose steroids alone, with a comparable safety profile. This finding is an important advancement in the treatment of patients with active lupus nephritis. Aurinia Pharmaceuticals.

Pembrolizumab-induced myasthenia gravis-like disorder, ocular myositis, and hepatitis: a case report

IntroductionPembrolizumab and other immune checkpoint inhibitors are the emerging treatment for selected, high-grade malignancies. However, a small number of patients are unable to tolerate its adverse effects, leading to discontinuation of this potentially life-changing therapy. In this study, we present a case of high-grade urothelial carcinoma patient, who experienced neurocomplications during the first pembrolizumab administration. However, we were able to limit the adverse effect by concomitant use of low-dose oral steroids.Case presentationA 75-year-old Taiwanese female with high-grade urothelial carcinoma of the left ureter came to the neurology clinic with complaints of acute onset of bilateral ptosis 16 days after her first infusion of pembrolizumab. It was found that she developed complete bilateral ptosis and limited extraocular muscle movements. Myasthenia gravis-related antibodies and repetitive stimulation test were negative. We diagnosed her with pembrolizumab-induced myasthenia gravis-like disorder and myositis based on clinical symptoms and elevation of muscle enzymes. We commenced methylprednisolone pulse therapy followed by oral steroid therapy with gradual resolution of the symptoms. Three months later, the patient received a second cycle of pembrolizumab with low-dose oral steroids without any complications.ConclusionPembrolizumab exerts its antitumor activity by interfering with the binding of programmed death 1 and its ligand, programmed death ligand 1. As a result, enhanced cytotoxic T cells can recognize tumor cells and induce cellular death. However, neurological complications may be severe and require prompt recognition and treatment. Our case demonstrated that concomitant use of low-dose steroids and pembrolizumab might prevent such complications.

Evidence of Cochlear Synaptopathy and the Effect of Systemic Steroid in Acute Idiopathic Tinnitus With Normal Hearing.

To evaluate the electrophysiologic evidence of cochlear synaptopathy and the effects of systemic steroids in acute idiopathic tinnitus with normal hearing. Retrospective review of medical data. Tertiary referral center. Fifty-nine patients who experienced acute-onset idiopathic tinnitus (within 12 weeks) with normal hearing and the same number of age- and pure-tone threshold-matched control groups. Electrophysiologic studies of the auditory pathway, oral steroids, and ginkgo biloba. Pure-tone thresholds, wave I and wave V amplitudes of the auditory brainstem response (ABR), tinnitus handicap inventory (THI), and visual analog scale (VAS). Significantly reduced ABR wave I amplitude and wave I/wave V ratio were found in the tinnitus group compared with the no tinnitus group. Age and pure-tone threshold were significantly correlated with reduced wave I amplitude and small wave I/wave V ratio. The THI and VAS scores were decreased at 3 and 12 weeks after steroid administration; however, overall changes in THI and VAS scores were not significantly different between the steroid and ginkgo biloba groups. Potential cochlear synaptopathy was suspected in the early stage of acute idiopathic tinnitus, even in patients with normal hearing. Age and hearing threshold were potentially associated with the development of cochlear synaptopathy. Low-dose oral steroids and ginkgo biloba induced early subjective relief of tinnitus, which maintained up to 12 weeks, however, those changes did not differ between groups.

The Successful Treatment of Combined Local and Systemic Steroids in a Patient with Brachial Plexus Neuritis: A Case report

Brachial plexus neuritis (BPN), also known as Parsonage-Turner syndrome, is an uncommon neurological disorder that can manifest with acute extreme upper arm pain followed by patchy muscle paralysis. There is no evidence supporting any recommended treatments for BPN from randomized trials. Non-randomized studies have supported the effectiveness of early administration of high-dose oral corticosteroids during the painful phase. We present a case of a 41-year-old-female with a history of acute left lateral shoulder pain and shoulder girdle weakness who was diagnosed with acute BPN. To reduce the risk of complications arising from high-dose oral steroid administration, we used an ultrasound-guided brachial plexus blockade combined with low-dose oral steroids. The combined treatment approach successfully restored shoulder function and effectively alleviated pain while avoiding complications associated with systemic steroid administration. Keywords: Brachial plexus neuritis; Interventional ultrasonography; Steroid

MO019AURORA PHASE 3 TRIAL DEMONSTRATES VOCLOSPORIN STATISTICAL SUPERIORITY OVER STANDARD OF CARE IN LUPUS NEPHRITIS (LN)

Abstract Background and Aims Voclosporin (VCS) is a novel high potency calcineurin inhibitor (CNI) with a favorable metabolic profile and a consistent predictable dose response potentially eliminating the need for therapeutic drug monitoring. The Aurinia Renal Response in Active Lupus with Voclosporin (AURORA) study, involving 357 patients with active LN, was a Phase 3 global, double-blind, placebo-controlled RCT designed to evaluate the efficacy and safety of VCS (23.7mg BID) vs placebo in combination with mycophenolate (MMF, 2 g/day) and rapidly tapered low dose oral steroids. Method The primary endpoint was renal response (RR) at 52 weeks. RR was defined as UPCR of ≤ 0.5 mg/mg, eGFR ≥ 60 mL/min, or no confirmed decrease from baseline in eGFR of &amp;gt; 20%, presence of sustained, low dose steroids and no administration of rescue medication. Results AURORA met its primary endpoint, achieving statistically superior RR rates of 40.8% for voclosporin vs. 22.5% for the control (OR 2.65, 95% CI; p &amp;lt; 0.001). The benefits of VCS were also seen for all predetermined secondary endpoints, achieving statistical significance in favor of VCS for RR at 24 weeks, partial renal response (PRR) at 24 and 52 weeks, time to achieve UPCR ≤ 0.5, and time to 50% reduction in UPCR. Prespecified confirmed eGFR decreases &amp;gt;30% were similar in both groups, with 10.1% reported in the VCS group and 10.2% in the control arm (p= 0.971). No significant differences were seen at any timepoints in the study. Furthermore, all pre-specified subgroup analyses (age, sex, race, biopsy class, region, and prior MMF use) also favored VCS. VCS was well tolerated with no unexpected safety signals. Similar SAEs were reported in the VCS group (20.8%) and in the control arm (21.3%). Infection was the most commonly reported SAE with 10.1% of VCS patients versus 11.2% of patients in the control arm. Overall mortality in the trial was low, with 6 deaths observed; 1 in the VCS arm and 5 in the control group. Additionally, the VCS arm showed no significant decrease at week 52 in eGFR or increase in BP, lipids or glucose. Conclusion While maintaining a comparable safety profile, VCS plus standard therapy achieved a statistically superior RR over one year compared to placebo plus standard therapy in adults with active LN.

P190 Non-GCA diagnoses from a GCA fast track clinic: a single centre with four years' experience (2016-2019)

Abstract Background Giant cell arteritis (GCA) has protean manifestations including temporal headache, visual disturbances, constitutional symptoms, jaw and tongue pain; symptoms which overlap with other conditions which mimic GCA. An important benefit of a fast-track clinic (FTC) is to rapidly exclude the diagnosis GCA to avoid inappropriate steroid exposure. We analysed data for patients referred with suspected GCA to our FTC where GCA diagnosis was subsequently excluded with fast-track ultrasound (US) and other investigations. Methods This retrospective data was extracted from the GCA fast-track electronic referral system at Southend University Hospital from January 2016 to July 2019. Results 1,057 patients were seen at the fast-track clinic in this study period (Table 1). 690 (65.28%) were females. Only 15% (159) of the participants had a confirmed diagnosis of GCA (majority using US but also with other investigations such as biopsy or PET CT). Non-GCA patients accounted for 85% (898) and had a variety of differential diagnoses. In 222 (23.7%) no additional diagnosis was made after excluding GCA and patients were referred back for an expectant follow-up and assessment should any new features develop. In 204 (22.7%), polymyalgia rheumatica (PMR) was diagnosed with classical clinical symptoms and US of bilateral glenohumeral joints or response to a trial of low dose oral steroids. Another major group had different types of headaches 141 (15.71%) at presentation mimicking GCA. This included migraine 79 (56.0%), cervicogenic 58 (41.13%) and cluster headaches 4 (2.83%). Infectious causes were limited to head and neck infections 89 (9.91%) such as periorbital swelling, shingles and sinusitis. Neurological causes such as cervical spondylosis, cranial nerve palsy and TIA contributed to 7.9%. Chronic pain and other causes contributed 74 (8.24%) and 97 (10.8%) respectively. Other causes included medication-related (33), stress (21), cancer (4), RS3PE (4), glaucoma (2) and ANCA-associated vasculitis (33). Conclusion An FTP clinic not only diagnoses GCA rapidly but is also able to rapidly screen non GCA and prevent unnecessary steroid treatment. It also requires a screening tool like GCA probability score to triage referrals to enable a more efficient service. Disclosures A. kayani None. A. Sebastian None. C. Ranasinghe None. M. Whitlock None. H. Hussain None. B. Dasgupta Consultancies; Roche, Sanofi, GSK. Grants/research support; Roche.

Use of Oral Prednisolone and a 3-Phase Bone Scintigraphy in Patients with Complex Regional Pain Syndrome Type I.

To compare the treatment effects of a high-dose and low-dose oral steroid regimen based on changes in the radioisotope uptake ratio (RUR) observed from three-phase bone scintigraphy (TPBS) in patients with complex regional pain syndrome type I (CRPS I), we retrospectively analyzed data of 34 patients with CRPS I from traumatic brain injury and stroke. Depending on the dose of steroid administered, patients were divided into high-dose (n = 14) and low-dose steroid groups (n = 20). We compared the severity scores, Kozin’s classification scores, and RUR observed from TPBS between the two groups. There were significant changes in the severity scores and Kozin’s classification between the baseline and 2 weeks from baseline (p < 0.05), however, there were no significant differences in terms of changes in the scores, classification, or the RUR observed from TPBS at 2 weeks from baseline (p > 0.05). There were no treatment-emergent adverse events (TEAEs) such as blood pressure elevation, impaired glycemic control, or gastrointestinal disturbances. Our results indicate that the efficacy profile of a low-dose oral steroid regimen is comparable to that of a high-dose regimen in alleviating symptoms in CRPS I patients. However, additional prospective, large-scale, multi-center studies are warranted to confirm our results.

Hypophysitis: A Rare Cause of Impaired Consciousness in a Middle-Aged Woman

Hypophysitis occurs predominantly in women, usually during pregnancy or postpartum period. Hypophysitis involving the anterior pituitary often presents with adrenal insufficiency. We describe a 43-year-old woman who presented with recurrent episodes of alteration of sensorium due to hyponatremia. She had a 3-month history of amenorrhea and on evaluation had evidence of pan-hypopituitarism. The magnetic resonance images of the brain showed mild pituitary enlargement and thickened pituitary stalk with homogenous contrast enhancement indicating hypophysitis. She was treated with oral steroids and thyroxine supplements. She remained asymptomatic at 15-month follow-up on low-dose oral steroids and thyroxine supplements. Hypopituitarism due to hypophysitis resulted in recurrent episodes of hyponatremia in our patient. Our case highlights the importance of a systematic search for the etiology for hyponatremic encephalopathy.

Relative adrenal insufficiency post-discontinuation of topical steroids in a patient with acute lymphoblastic leukemia

Abstract Accelerated cortisol production is observed in patients with severe infections, trauma, burns, illness, and surgery. The cortisol levels observed in relative adrenal insufficiency are insufficient for controlling the inflammatory response. Sudden discontinuation of glucocorticoid therapy is one of the causes of relative adrenal insufficiency. A 63-year-old-man who had undergone cord blood transplantation for T-cell acute lymphoblastic leukemia (T-ALL) and had shown complete remission for 2 years was admitted to our hospital because of high fever, general fatigue, lowering blood pressure, and tachycardia. Physical, laboratory, and imaging examinations revealed T-ALL relapse and pneumonia. Although administration of antibacterial drugs and vasopressors relieved his symptoms and temporarily resolved his fever, he showed prolonged fatigue and mild fever; thus, we could not stop administering vasopressors. He had been using the following three types of topical steroids for chronic eczema for several years: betamethasone butyrate propionate, prednisolone valerate acetate, and hydrocortisone acetate. Thereafter, he had himself discontinued topical steroids because of general fatigue. We suspected his symptoms were caused by relative adrenal insufficiency due to sudden discontinuation of topical steroids; thus, we administered 100 mg of hydrocortisone intravenously. His fever resolved remarkably, and he resumed application of topical steroids and started oral steroid supplementation. His temperature was maintained in the normal range. He successfully achieved complete remission with salvage chemotherapy followed by a second transplantation; with the use of low-dose oral steroids, he did not develop relative adrenal insufficiency. Adrenal insufficiency is known to be caused by sudden discontinuation of oral steroids. Furthermore, we should pay attention to sudden discontinuation of topical steroids, which could cause relative adrenal insufficiency.