Corticosteroid Tapering Research Articles

Oral corticosteroid dosage and taper duration at onset in myelin oligodendrocyte glycoprotein antibody-associated disease influences time to first relapse

BackgroundWe sought to identify an optimal oral corticosteroid regimen at the onset of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), which would delay time to first relapse while minimising cumulative corticosteroid...

Combination ruxolitinib and belumosudil is tolerable and induces responses despite treatment failure as monotherapies

FDA approved agents for the treatment of chronic GVHD including ruxolitinib and belumosudil are effective steroid-sparing agents, with overall response rates (ORR) of 76% and 65% respectively. Ruxolitinib and belumosudil are well tolerated with different primary targets. Little data is available on the use of combination ruxolitinib and belumosudil. This is a single center, retrospective analysis of 20 treatment-refractory patients with chronic GVHD treated with combination ruxolitinib and belumosudil. The ORR including complete response (CR) and partial response (PR) at any time was 55% (11/20). Among responding patients, other immunosuppressive agents were tapered or discontinued in all patients. None of the patients developed EBV or CMV reactivation requiring treatment. 4 patients (20%) developed pneumonia and 2 patients (10%) developed viral URI. Cytopenias were not exacerbated. No patients had graft failure or relapsed disease. The combination is tolerable, delays the need for alternative therapies, and facilitates tapering of corticosteroids.

Efficacy and safety of tocilizumab in Chinese patients with systemic juvenile idiopathic arthritis: a multicentre phase IV trial

ObjectivesGiven the limited tocilizumab (TCZ) treatment data for systemic juvenile idiopathic arthritis (sJIA) in China, we evaluated the long-term efficacy and safety of TCZ in Chinese patients with sJIA.MethodIn this multicentre, interventional Phase IV study, patients with sJIA and inadequate clinical response to non-steroidal anti-inflammatory drugs/corticosteroids received TCZ infusions every 2 weeks based on body weight (< 30 kg, 12 mg/kg; ≥ 30 kg, 8 mg/kg), over a 52-week open-label period and an 8-week safety follow-up period. The primary endpoint was the proportion of patients with a JIA American College of Rheumatology (ACR) 30 response and absence of fever at Week 12.ResultsSixty-two patients were enrolled and treated (12-mg/kg group, 34; 8-mg/kg group, 28). At Week 12, 87.1% (95% confidence interval 78.8%–95.4%) of patients had JIA ACR 30 response and absence of fever; Week 52 results were similar. The proportion of JIA ACR 30/50/70/90 responders rapidly increased at Week 12, up to Week 52. High-sensitivity C-reactive protein (hsCRP) levels decreased within 4 weeks; 44/58 patients (75.9%) with elevated baseline hsCRP recovered at Week 52. Childhood Health Assessment Questionnaire pain scores, disability index scores, and mean corticosteroid dose decreased over time. Height standard deviation score changes at Week 52 indicated catch-up growth. Most adverse events (AEs) were mild (serious AE incidence, 17.7%). No deaths or macrophage activation syndrome occurred.ConclusionThis is the first multicentre trial to report the efficacy and safety of TCZ in Chinese patients with sJIA at 52 weeks. No new safety concerns were found.Key points• This is the first multicentre trial providing strong evidence for tocilizumab (TCZ) treatment for systemic juvenile idiopathic arthritis (sJIA) in China.• The study reported TCZ had good efficacy and favourable safety profiles in Chinese sJIA patients in the long term (52 weeks).• TCZ treatment showed rapid disease control, which was maintained over time, catch-up growth benefits in patients, tapering and discontinuation of corticosteroids, and improved quality of life.

Outcomes of Cyclosporine Ophthalmic Emulsion 0.05% Use in Pediatric Blepharokeratoconjunctivitis

Purpose: Pediatric blepharokeratoconjunctivitis (BKC) is a chronic ocular surface inflammatory disease. In this article, we report our experience using low-dose topical cyclosporine (CsA) 0.05% for the treatment of pediatric BKC. Methods: A retrospective review was conducted on pediatric patients treated with topical CsA 0.05% for BKC between 2018 and 2022 at a single academic institution. Patients with less than 6 weeks of follow-up, a history of ocular infectious disease, or previous usage of topical/systemic immunomodulators (except corticosteroids) were excluded. The primary outcome was the change in the number of episodes of disease reactivation (flare) before and after the use of CsA 0.05%. Secondary outcomes included the number of clinic visits per year, success rate in corticosteroid tapering, and usage of rescue topical corticosteroid. Results: A total of 21 patients (13 male patients and 8 female patients) treated with CsA 0.05% twice daily were included in this study. The mean age of patients was 9.7 ± 4.2 years, and the mean follow-up period was 62.2 ± 62.5 weeks. The median number of flares per year was 5.6 (95% CI, 3.9–7.3) before treatment with CsA 0.05%, which reduced to 0.0 (95% CI, 0.0–0.9) while on CsA 0.05% (P = 0.01). The median number of clinic visits significantly reduced from 9.5 (95% CI, 7.3–11.7) to 4.5 (95% CI, 3.7–6.8) visits per year (P &lt; 0.0001). After 3.5 ± 2.7 weeks, 90.4% of patients using topical CSs concomitantly with topical CsA 0.05% could be successfully tapered off their topical CSs. Of the patients who tapered off their topical CSs, 3 patients (15%) later required rescue topical CSs despite ongoing CsA 0.05% treatment because of acute flare episodes. No adverse effects were reported with CsA use. Conclusions: This study demonstrates the efficacy of low-dose topical CsA 0.05% in reducing the frequency of acute flares and clinic visits per year in pediatric BKC.

Therapeutic Doses of Efzofitimod Demonstrate Efficacy in Pulmonary Sarcoidosis

BackgroundIn a phase 1b/2a clinical trial of efzofitimod in patients with corticosteroid-requiring pulmonary sarcoidosis, treatment resulted in dose-dependent improvement in key endpoints. We undertook a post hoc analysis pooling dose arms that achieved therapeutic concentrations of efzofitimod (Therapeutic group)versusthose that did not (Subtherapeutic group).MethodsPeripheral blood mononuclear cells incubated with tuberculin-coated beads were exposed to varying concentrations of efzofitimod in anin vitroassay to determine concentrations that inhibited granuloma formation. In the post hoc analysis, we compared time-to-first-relapse and changes in pulmonary function after a protocolised corticosteroid taper in the Therapeutic and Subtherapeutic groups.ResultsEfzofitimod at ≥300 nM (19 µg·mL−1) inhibited granuloma formationin vitro. Based on average efzofitimod serum concentrations achieved in the phase 1b/2a study, the 3 and 5 mg·kg−1dose arms were pooled as the Therapeutic group, while the 1 mg·kg−1arm was pooled with the placebo arm as the Subtherapeutic group. Relapse rates were 54.4% and 7.7% in the Subtherapeutic group and Therapeutic group, respectively. Median time-to-first-relapse in the Subtherapeutic group was 126 days, whereas in the Therapeutic group, only one of 17 patients relapsed by the end of the 24-week study (p=0.017). Slopes analysis showed that forced vital capacity increased in the Therapeutic group, but decreased in the Subtherapeutic group, over the course of the trial (p=0.035).ConclusionTreatment with efzofitimod at therapeutic doses, as compared with a subtherapeutic dose or placebo, was associated with a lower rate of relapse as corticosteroids were tapered.

Immune-related encephalitis after immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but can trigger immune-related encephalitis. We report one of the largest case series of patients with immune-related encephalitis and review of the literature. Retrospective series of patients with immune-related encephalitis and literature review. Fourteen patients with cancer treated with ICI (50% combination therapy) developed immune-related encephalitis. Diagnostic testing revealed cerebral spinal fluid (CSF) lymphocytic pleocytosis (85%) and elevated protein (69%), abnormal brain magnetic resonance imaging(MRI) (33%) or brain FDG-PET (25%), electroencephalogram (EEG) abnormalities (30%), and autoantibodies (31%). Encephalitis treatment included: corticosteroids (86%), intravenous immunoglobulin (IVIg) (36%), plasmapheresis (7%), and rituximab (29%). There were no deaths and 12 patients had significant recovery, although long-term complications were observed. All patients discontinued ICI. Longitudinal follow-up demonstrated anti-cancer response to ICI at 3 months (85%) and 6 months post-ICI initiation (77%). A literature review identified 132 patients with immune-related encephalitis. Most were treated with PD-1 inhibitors (18% combination). Common abnormalities included elevated CSF protein (84%) or pleocytosis (77%), abnormal brain MRI (65%), or autoantibodies (47%). Nearly all were treated with corticosteroids, many required additional therapy with IVIg (26%) or rituximab (12%). Most patients had clinical improvement (81%) but a minority (10%) had a clinical relapse after completing corticosteroid taper. ICIs were resumed in 7 patients (5%), with relapse in 3. Immune-related encephalitis is treatable and improves with corticosteroids in most cases but may require additional immunosuppression. Re-emergence of encephalitis is rare and does not typically result in adverse outcomes, and this should be considered in neurological immune-related adverse event management guidelines.

Efficacy and safety of risankizumab by baseline corticosteroid use and achievement of corticosteroid-free clinical and endoscopic outcomes in patients with moderately to severely active Crohn's disease.

Risankizumab is efficacious and well tolerated in adults with moderately to severely active Crohn's disease (CD). To evaluate the corticosteroid-sparing effect of risankizumab in CD. During the 12-week induction period, patients maintained stable baseline corticosteroid doses, up to 20 mg/day prednisone or equivalent. At week 0 of maintenance, a mandatory corticosteroid taper was started. This post hoc analysis evaluated corticosteroid-free clinical and endoscopic outcomes at week 52 of maintenance; safety was also assessed. Of 889 patients randomised to induction with risankizumab 600 mg or placebo, 285 (32.1%) were taking baseline concomitant corticosteroids. Week 12 clinical remission and endoscopic response rates were greater for risankizumab 600 mg versus placebo, regardless of concomitant corticosteroid use. At week 52, 66.7%, 50.0% and 41.2% of patients taking risankizumab 180 mg, risankizumab 360 mg and (withdrawal) placebo, respectively, discontinued corticosteroids. Week 52 corticosteroid-free clinical remission per stool frequency/abdominal pain score (risankizumab 180 mg [42.7%] or 360 mg [49.8%]; [withdrawal] placebo [39.0%]), corticosteroid-free clinical remission per Crohn's Disease Activity Index (risankizumab 180 mg [51.0%] or 360 mg [49.5%]; [withdrawal] placebo [40.2%]), and corticosteroid-free endoscopic response (risankizumab 180 mg [44.6%] or 360 mg [44.7%]; [withdrawal] placebo [20.7%]) rates were greater for risankizumab than placebo. Adverse event rates were generally similar,regardless of baseline corticosteroid use. Efficacy of risankizumab 600 mg induction therapy was independent of concomitant corticosteroid use. Risankizumab 180 and 360 mg maintenance therapy yielded high rates of corticosteroid-free clinical and endoscopic outcomes at week 52.

Impact of Durvalumab on the Duration and Complexity of Corticosteroid Therapy for Pneumonitis After Chemoradiotherapy

IntroductionIt is unclear how the duration and tapering pattern of corticosteroid therapy for pneumonitis changed after the introduction of durvalumab consolidation therapy. MethodsWe retrospectively evaluated the medical records of patients diagnosed with nonsmall cell lung cancer who received chemoradiotherapy between January 2014 and December 2020. ResultsData for 135 patients treated before durvalumab approval and 100 patients treated with durvalumab after its approval were analyzed. In both groups, more than 70% were male, with a median age of 66 y. Approximately 85% were smokers, and the most common tumor histology was adenocarcinoma. Most patients were treated with doses of 60 and 66 Gy (n = 127 [94%] vs. n = 95 [95%]). Among the patients treated with durvalumab, 57%, 38%, and 5% had grade 1, grade 2, and grade 3 pneumonitis; none had grade 4 or 5 pneumonitis. Patients treated with durvalumab exhibited a longer duration of corticosteroid therapy for pneumonitis (17 wk; range: 2-88 wk) than patients not treated with durvalumab (7 wk; range: 0.4-21 wk; P < 0.001). Pneumonitis relapse was more frequent in patients treated with durvalumab (n = 8; 23%) than in patients not treated with durvalumab (n = 2; 7%). Among the 8 patients treated with durvalumab, 2 had recurrent pneumonitis, 1 could not terminate corticosteroids. ConclusionsOur data show that durvalumab prolongs the duration of corticosteroid therapy and increases the complexity of corticosteroid tapering patterns. This study can help manage pneumonitis caused by immune checkpoint inhibitors and other drugs used after chemoradiotherapy in routine practice and clinical trials.

Outcomes in Patients With Vogt–Koyanagi–Harada Disease From the First-Line Antimetabolites for Steroid-Sparing Treatment Uveitis Trial

PurposeTo compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease. MethodsA subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX versus MMF) and disease stage (acute versus chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25mg weekly oral MTX or 1.5g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD). ResultsNinety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P=.12) or in BSCVA improvement (P=.78). Methotrexate was superior to MMF in reducing CST (P=.003) and resolving SRD (P=.02). There was no significant difference in treatment success by disease stage (P=.25), but patients with acute VKH had greater improvement in BSCVA (P<.001) and reduction of CST (P=.02) than chronic VKH patients. ConclusionsMTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. Trial RegistrationClinicalTrials.gov Identifier: NCT 0182929

Real-world experience with fostamatinib in patients with immune thrombocytopenia: Results of an observational study (FORTE).

e23289 Background: Immune thrombocytopenia (ITP) is an autoantibody-mediated disease in which platelets are prematurely phagocytosed by Fcg-receptor-bearing macrophages in a spleen tyrosine kinase (SYK)-dependent signaling pathway. Corticosteroids (CS) are used to suppress the immune response, but long-term use carries a heavy burden of toxicity. Subsequent treatments for ITP include fostamatinib, a potent oral SYK inhibitor approved in 2018 based on two randomized, placebo-controlled, phase 3 trials. In trial patients, who received fostamatinib as second-line therapy following CS with or without immunoglobulins (IVIG), 25 of 32 (78%) patients achieved a platelet response of ≥50,000/µL, which was sustained for a median of 83% of treatment days. Here, we report real-world experience with fostamatinib as second-line therapy for ITP from a multi-center, prospective, observational study. Methods: The study (FORTE; NCT04904276) enrolled adult patients with ITP and an insufficient response to prior CS and/or IVIG. Patients were treated according to their clinician’s discretion, and data were collected for up to 12 months at clinic visits. Results: Sixteen patients were enrolled, and 15 were treated. Of the 15, 9 (60%) were female and the median age was 48 years (range, 20-92). 12 (80%) patients had prior CS and 6 (40%) prior IVIG. 7 (47%) patients completed the study and 8 discontinued treatment due to adverse events (4), lack of efficacy (2), and patient decision (2). After initiation of fostamatinib, 93% (14/15) of patients achieved ≥1 platelet count ≥50,000/μL. Median platelet count increased over time from 43,000/μL (IQR 19,000-105,000) at baseline to 167,000/μL (IQR 96,000-180,000) at Month 12. The median cumulative duration of elevated platelet count was 32 weeks (IQR 6.4-49.4). Concomitant CS were used by 7 (47%) patients at baseline, all of whom were able to taper as early as Month 1 and discontinue their dose by Month 3 in 4 patients, Month 6 in 2 patients, and Month 9 in 1 patient. Five patients had ITP-related AEs (4 Grade 1 and 1 Grade 2): gingival bleeding (2), mucosal haemorrhage (2), fatigue (1), contusion (3), headache (1) and epistaxis (1). There were 3 serious AEs in 2 patients: Grade 3 diarrhea in 1 and Grade 2 dyspnea and chills in 1. Overall safety results were consistent with previous studies of fostamatinib. Conclusions: Real world use of fostamatinib as documented in this observational study demonstrated efficacy and safety as second-line therapy for ITP. Fostamatinib allowed successful tapering and discontinuation of CS while maintaining platelet counts above 50,000/μL. Clinical trial information: NCT04904276 .

Sarilumab (Kevzara) for polymyalgia rheumatica.

The FDA has approved the interleukin (IL)-6 inhibitor sarilumab (Kevzara – Sanofi/Regeneron) for treatment of polymyalgia rheumatica (PMR) in adults who had an inadequate response to corticosteroids or cannot tolerate a corticosteroid taper.

A case of refractory peripheral neuropathy associated with eosinophilic granulomatosis with polyangiitis with successful tapering of systemic corticosteroid and reduced dosing frequency of high-dose intravenous immunoglobulin after combined use of mepolizumab

A case of refractory peripheral neuropathy associated with eosinophilic granulomatosis with polyangiitis with successful tapering of systemic corticosteroid and reduced dosing frequency of high-dose intravenous immunoglobulin after combined use of mepolizumab

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.

Through Indian Eyes: A Case Series on Steroid-induced Secondary Cataract

Lichen planus, a chronic autoimmune dermatological disorder, often necessitates the use of topical corticosteroids for symptom management. However, this case series highlights the emergence of topical steroid-induced secondary cataracts in two patients, emphasizing a previously underrecognized complication. Both patients, females aged 36 and 43, presented with gradual vision loss in their left eyes, attributed to prolonged corticosteroid use for lichen planus and skin allergies, respectively. Ophthalmological examinations confirmed the diagnosis, leading to cataract surgeries. The pathogenesis involves complex cellular and molecular mechanisms, emphasizing the need for vigilant monitoring during corticosteroid therapy. Moreover, the lack of stringent reporting systems for adverse drug reactions in India underscores the necessity for comprehensive monitoring to mitigate economic and quality of life burdens. The study emphasizes the importance of judicious corticosteroid use, tapering regimens, and patient education to minimize complications while effectively managing dermatological conditions. This underscores the critical need for heightened awareness, surveillance, and patient-centred approaches to mitigate the risk of corticosteroid-induced secondary cataracts, ensuring optimal therapeutic outcomes and long-term ocular health.

Severe Recurrence and Retinal Inflammatory Infiltration After Cessation of Immunosuppression for Multifocal Choroiditis and Panuveitis.

To describe a severe recurrence of intraocular inflammation following the cessation of immunosuppression, previously administered for multifocal choroiditis and panuveitis (MCP). Retrospective chart review. A 27-year-old woman with MCP initially was treated with intravenous and oral corticosteroids and photodynamic therapy because of an active macular neovascularization in both eyes. Mycophenolate was soon started and the recurrences during tapering of the oral corticosteroids in the first months were treated with periocular corticosteroids and anti-vascular endothelial growth factor injections as they became available. After a decade of immunosuppression without recurrences, the patient, having relocated, discontinued mycophenolate upon the advice of a new ophthalmologist who diagnosed her with punctate inner choroidopathy. This led to a severe recurrence in both eyes, characterized by new inflammatory lesions, ellipsoid zone loss, and widespread inflammatory cell infiltration into the outer retina. Intravitreal triamcinolone injections resulted in the resolution of sub- and intraretinal inflammatory lesions and ellipsoid zone defects. The abrupt discontinuation of immunosuppression in a patient with MCP was associated with a rebound phenomenon, characterized by multi-level inflammatory activity in the posterior pole. This rebound phenomenon may offer clues as to the inflammatory targets in MCP.

New-Onset, Treatment-Resistant Inflammatory Bowel Disease after Administration of Secukinumab for Plaque Psoriasis: A Case Report and Review of the Existing Literature.

Aberrant activation of the IL-23/IL-17 axis leads to inflammatory phenotypes with overlapping clinical characteristics. Inhibition of IL-17 has mostly an anti-inflammatory effect, but sporadic cases of new-onset IBD have been reported. We present the case of a 65-year-old male patient with new-onset Crohn's-like disease after treatment with secukinumab for skin psoriasis. Discontinuation of the IL-17 inhibitor and high-dose corticosteroid treatment were efficient initially, but a relapse was noted during corticosteroid tapering. Administration of certolizumab pegol did partially relieve the patient, but disease remission was only achieved with subcutaneous risankizumab therapy. Clinical trials and real-world data indicate sporadic cases of new-onset IBD in patients receiving IL-17 inhibitors. Interestingly, our case is a "treatment-resistant" one since treatment with a biologic disease-modifying drug (bDMARD) usually leads to disease remission. As such, it is crucial to investigate the special characteristics of this clinical entity.

Prednisolone-Induced Cushing's syndrome: A case report

Objective: Prednisolone, a frequently prescribed corticosteroid, is linked to diverse adverse effects, including Cushing's syndrome. Material and Methods: This report details a case of prednisolone-induced Cushing's syndrome in a 6-year-old girl diagnosed with Acute Disseminated Encephalomyelitis (ADEM). Prednisolone was administered to manage inflammation associated with ADEM. Subsequent to the tapering of prednisolone, the patient exhibited progressive weight gain, facial rounding, fatigue, and muscle weakness. Clinical examination revealed classic manifestations of Cushing's syndrome, including central obesity, moon facies, and proximal muscle weakness. Laboratory analysis confirmed elevated serum cortisol levels and suppressed adrenocorticotropic hormone (ACTH), confirming exogenous Cushing's syndrome induced by prednisolone. The patient's prednisolone dosage was gradually reduced under careful medical supervision. Regular follow-ups were conducted to monitor symptoms, weight fluctuations, and hormonal levels. With the decrease in prednisolone dosage, the patient's symptoms showed gradual improvement. Results and conclusion: Prednisolone-induced Cushing's syndrome arises as a recognized complication of corticosteroid therapy, primarily characterized by the suppression of the hypothalamic-pituitary-adrenal axis. Early awareness of this adverse effect is pivotal for prompt identification and management. This case emphasizes the significance of vigilant monitoring and judicious use of prednisolone to mitigate adverse effects like Cushing's syndrome. Swift recognition, dose adjustments, and a gradual tapering of corticosteroids play a crucial role in effectively managing this condition for optimal patient outcomes.

P932 Corticosteroid-sparing effect of mirikizumab for the treatment of moderately-to-severely active Ulcerative Colitis: Extended induction subgroup analysis from Phase 3 trial

Abstract Background Mirikizumab, an anti-IL-23p19 antibody, has demonstrated efficacy and safety in moderately-to-severely active ulcerative colitis (UC) Phase 3 trials (LUCENT-1 and -2; NCT03518086, NCT03524092).1 A treatment goal for patients with UC is corticosteroid (CS)-free remission. We assessed the CS-sparing effect of mirikizumab among the extended induction patient population receiving CS at induction baseline. Methods In LUCENT-1, patients in the modified intention to treat mirikizumab group (n=868) received mirikizumab 300 mg intravenously (IV) at Week (W)0, W4, and W8. Patients receiving mirikizumab on CS at baseline (n=351) remained on their stable baseline dose (prednisone ≤20 mg/day or equivalent, budesonide MMX 9 mg/day, or beclomethasone 5 mg/day) during induction (W0 to W12). Patients not achieving clinical response (≥2-point and ≥30% decrease in Modified Mayo Score from baseline; and rectal bleeding=0 or 1, or ≥1-point decrease from baseline) at W12 (n=272) entered LUCENT-2 open label (OL) extended induction and received 300 mg mirikizumab IV at W12, W16, and W20. Extended induction responders at W24 (n=144) entered OL maintenance and received 200mg mirikizumab subcutaneously (SC) Q4W until W52. CS taper was initiated if clinical response was achieved at W24 or earlier based on investigator discretion if symptomatic improvement was evident. Patients who discontinued CS and remained off throughout the study were considered "discontinued." Descriptive statistics for efficacy outcomes were summarized. Missing data were imputed as non-response. Results Of the 272 mirikizumab patients in the extended induction population, 118 received CS at induction baseline. The mean prednisone equivalent dose was 15mg. At W24, among the 62/118 (52.5%) who achieved clinical response and continued with maintenance, 8 (12.9%) discontinued CS, 2 (3.2%) achieved clinical remission off CS, and 8 (12.9%) achieved symptomatic remission off CS. At W52, 43/62 (69.4%) of the extended induction responders discontinued CS, 18 (29.0%) achieved clinical remission off CS, and 37 (59.7%) achieved symptomatic remission off CS. Among patients with non-missing data who completed W52 of mirikizumab treatment, 89.6% had discontinued CS (Table). Conclusion Nearly 70% of extended induction responders discontinued CS by W52. CS-sparing effect of mirikizumab in patients with moderately-to-severely active UC is clinically meaningful and aligns with the treatment goal of CS discontinuation.

P930 Rapid symptomatic improvement with subcutaneous infliximab induction treatment for patients with moderate-to-severe Crohn’s disease: first results from the DIRECT-CD study

Abstract Background Subcutaneous (SC) formulation of infliximab (IFX) received regulatory approval for the maintenance treatment of Crohn’s disease (CD) in 2020. DIRECT-CD is an ongoing multicentre trial to evaluate the efficacy of SC IFX induction and maintenance treatment in monotherapy versus combination therapy in CD (EUDRACT 2021-000469-33). Here we aimed to determine the rapidity of symptom improvement during this SC IFX induction regimen. Methods Patients with moderate-to-severe CD (Crohn’s disease activity index [CDAI]) &amp;gt;220 and endoscopic ulceration) received fixed SC IFX induction doses of 240 mg at Week 0 and 2, followed by maintenance treatment (120 mg every other week). We analysed diary PRO-2 entries (stool frequency and abdominal pain) through 14 days from the first injections of SC IFX. CDAI was assessed at Week 0, 2, 4 and 8. Changes in biochemical parameters were assessed (C-reactive protein [CRP]: Week 4 and 8; faecal calprotectin [FC] at Week 8). Combined corticosteroid-free remission (CSFR) was defined as CDAI&amp;lt;150 and CRP≤5 mg/L or FC≤250 mg/kg and complete tapering of corticosteroids. Results Twenty-five patients completed 8 weeks of treatment (60% female, median age 30 years [IQR 24-45], median weight 66.6 kg [IQR 64.0-89.5], median disease duration 4 years [IQR 1-8], 64% had ileocolonic disease [L3] and 76% exhibited an inflammatory phenotype [B1], 52% were using concomitant immunomodulators, and 28% were on stable dose of steroids). On the first day after the initial dose of SC IFX (240 mg), a significant decrease in PRO-2 was observed compared to baseline (5 [IQR 3-9] vs 8 [IQR 7-10], P&amp;lt;0.001) and this response was sustained throughout day 14 (P&amp;lt;0.001, Figure 1). At all measured time points, CDAI decreased significantly compared to baseline (Week 0: 313 [IQR 271-402]; Week 2: 245 [IQR 140-296], P&amp;lt;0.001; Week 4: 218 [101-258], P&amp;lt;0.001; Week 8: 172 [127-260], P&amp;lt;0.001). Combined CSFR was reached in 30% and 57% of all patients at Week 4 and 8, respectively. Median CRP was lower at Week 4 compared to baseline CRP (2.8 mg/L [IQR 0.7-4.9] vs 7.1 mg/L [IQR 2.1-26.3], P=0.001), a significant drop of FC was observed at Week 8 compared to baseline (77 mg/kg [IQR 37-847] vs 1385 mg/kg [IQR 219-3093], P&amp;lt;0.001). Conclusion Induction treatment with SC IFX provided a rapid decrease of abdominal pain and diarrhoea as early as day one. CDAI, CRP and FC decreased significantly at the earliest time point of evaluation (Week 2-8). DIRECT-CD is an ongoing clinical trial.

A Case in which Eosinophilic Meningoencephalitis Occurred during Oral Corticosteroid Tapering and after Switching from Anti-IL-5 to Anti-IgE Treatment.

A 49-year-old man with severe eosinophilic asthma, sinusitis, and esophagitis was admitted with a sudden severe headache. The patient was diagnosed with eosinophilic meningoencephalitis based on frontotemporal abnormalities on brain magnetic resonance imaging and high eosinophil counts in the cerebrospinal fluid. His allergic-disease control levels were poor, requiring regular oral corticosteroid (OCS) use. He was switched from anti-interleukin (IL)-5 to anti-IgE therapy because of worsening urticaria and asthma symptoms during OCS tapering. We suspect this was a case of complex eosinophilic meningoencephalitis caused by the combination of OCS tapering and anti-IL-5 therapy cessation that acquired anti-IgE antibody sensitization based on positive drug-induced lymphocyte stimulation test results.