Concomitant Corticosteroid Research Articles

Factors affecting 1-year persistence with vedolizumab for ulcerative colitis: a multicenter, retrospective real-world study.

The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response. In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled. Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00-7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13-0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response. Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence.

Safety and efficacy of the ROCK-2-inhibitor Belumosudil in cGvHD treatment - a retrospective, German-Swiss multicenter real-world data analysis.

Belumosudil is a first in class ROCK2-inhibitor approved by the FDA for the 3rd line treatment of chronic graft-versus-host disease (cGvHD). In this retrospective real-world analysis, we report safety and efficacy data of belumosudil treatment from 5 German/Swiss transplant centers. A total of 33 adult patients (median age 59 years) with moderate (n = 2) or severe (n = 31) cGvHD were treated on individual request due to lack of EMA approval. The patient cohort had a long history of cGvHD (median 44 months) and was heavily pretreated (median 4 prior lines). The overall response rate was 42% (95%CI, 25-60%) including organ responses in all organs except the liver (n = 2). The median time to response was 3 months (range, 1-9 months) and 8 of 14 patients (57%) had a durable response at last follow-up. One-third of patients had at least a 50% reduction in concomitant corticosteroid dosage. Median failure-free survival and median overall survival were 16.5 and 23.1 months, respectively. Adverse events ≥CTCAE grade 3 were reported in 27% of patients, with a predominance of infectious events, including one fatal course. The results are consistent with previous prospective trials including a favorable safety profile, while acknowledging the challenges of a heavily pretreated patient cohort.

Vidofludimus Calcium in Patients with Moderate-to-Severe Ulcerative Colitis: A Randomized, Placebo-Controlled, Phase 2 Trial.

Vidofludimus calcium (VidoCa) is a dihydroorotate dehydrogenase (DHODH) inhibitor that demonstrated efficacy in immune-related diseases. This study assessed the safety and efficacy of VidoCa in patients with active ulcerative colitis (UC). This placebo-controlled, phase 2 trial randomized adults with moderate-severe UC to receive once-daily VidoCa (10, 30, or 45 mg) or placebo for 10 weeks (induction); patients with symptomatic remission were re-randomized to VidoCa 10, 30 mg, or placebo once-daily for an additional 40 weeks (maintenance). The primary endpoint was clinical remission at Week 10. Secondary endpoints included symptomatic remission, endoscopic healing, and symptomatic response. The study is registered with ClinicalTrials.gov (NCT03341962) and EudraCT (2017-003703-22). 263 patients were randomized to induction treatment with VidoCa (10 mg [n=67)], 30 mg [n=66], 45 mg [n=66]) or placebo (n=64). Sixteen (14%) patients treated with VidoCa (30 mg or 45 mg) achieved the primary endpoint compared to 8 (14%) with placebo. In patients without concomitant corticosteroids, 7 [12%] treated with VidoCa achieved clinical remission at Week 10 vs. 1 [4%] with placebo. At Week 50, dose-dependent increases in the rate of clinical remission (p=0.0358), steroid-free clinical remission, and endoscopic healing were observed. Common adverse events (AEs) were headache (4 [6%]), anemia (3 [6%]), vomiting (3 [5%]), and hypertension (3 [5%]) with incidence similar between placebo and VidoCa. Hematuria (4 [6%]) was a treatment-related AE with VidoCa 45 mg only. The incidence of serious AEs was low. VidoCa was safe, well-tolerated, and demonstrated proof-of-concept for DHODH inhibition to treat UC.

Etrasimod as a Monotherapy or With Concomitant Use of Corticosteroids and/or Aminosalicylates: Results From the ELEVATE UC Clinical Program.

Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). We assessed the benefit of etrasimod monotherapy and the impact of concomitant corticosteroids (CS) and/or 5-aminosalicylates (5-ASA) therapy. In ELEVATE UC 52 and ELEVATE UC 12, patients with moderately to severely active UC were randomized 2:1 to etrasimod 2mg QD or placebo for 52 and 12 weeks, respectively. Oral CS or 5-ASA were allowed at baseline. Patients in the monotherapy subgroup received etrasimod or placebo without concomitant CS and/or 5-ASA at baseline. Predefined primary (clinical remission) and key secondary efficacy endpoints aligned with those from both trials and were assessed at Week 12 and Week 52. Safety was assessed up to Week 52. Clinical remission rates at Weeks 12 and 52 were significantly higher for etrasimod compared with placebo in patients receiving monotherapy (Week 12: 26.2% vs 4.8%; Week 52: 35.7% vs 4.0%). Differences vs placebo were statistically significant for all predefined endpoints at both time points in patients receiving monotherapy or etrasimod with concomitant 5-ASA only (all P < .05); numerical differences, due to small sample sizes, vs placebo were observed for all endpoints in the CS only and CS + 5-ASA subgroups. Safety was consistent with the overall population. Etrasimod monotherapy showed consistent efficacy and safety vs placebo; no apparent benefit was observed with concomitant CS and/or 5-ASA in patients receiving etrasimod. NCT03945188; NCT03996369.

Tofacitinib versus Vedolizumab Among Bio-naïve Patients with Ulcerative Colitis: A Real-World Propensity-Weighted Comparison.

Over the last decade, treatment options for moderate-to-severe ulcerative colitis (UC) have expanded. However, comparative studies between these agents are limited, especially among biologic-naïve patients. We aimed to compare the persistence, effectiveness and safety of tofacitinib and vedolizumab as the first advanced treatment for patients with UC. Patients who received either tofacitinib or vedolizumab as their first advanced therapy for UC in NHS Lothian were included. We used inverse probability of treatment weighting (IPTW). The probability of treatment assignment was calculated via logistic regression using age, sex, UC duration, Montreal extent, CRP, concomitant corticosteroids, and partial Mayo score at drug commencement. We included n=158 patients, of whom n=81 (51.3%) received vedolizumab and n=77 (48.7%) tofacitinib. Median follow-up for vedolizumab patients was 3.1 years (IQR 1.6-4.8) and for tofacitinib patients 1.5 years (IQR 0.3-2.3). The cohort was 59.5% male with a median age of 41.1 years (IQR 31.5-51.8). At two years, vedolizumab persistence was superior to tofacitinib (p=0.005). At week 12 and week 52 clinical, biochemical and fecal biomarker steroid free remission were comparable between groups. Primary non-response and secondary loss of response were 9.9% and 17.3% for vedolizumab and 23.4% and 13% for tofacitinib respectively. Frequency of adverse events was comparable (11 [13.6%] vedolizumab vs 19 [24.7%] tofacitinib, p=0.629). We found that the persistence and tolerability of vedolizumab was superior to tofacitinib in bio-naïve UC, although the rates of clinical and biomarker remission were comparable. These data may help inform positioning of advanced therapy.

Adjunct polymeric exclusive enteral nutrition helps achieve biochemical remission in active Crohn’s disease in adults irrespective of disease location and concomitant corticosteroid use

Background and aimData on the effectiveness of polymeric exclusive enteral nutrition (EEN) in inducing biochemical remission in adults with active Crohn’s Disease (CD) is scarce. We aimed to assess the...

Real-world treatment patterns, healthcare resource utilisation and costs in patients with SLE in the USA.

To evaluate the treatment patterns, medication adherence, concomitant corticosteroid use, factors influencing sequence of therapies (SOTs), healthcare resource utilisation (HCRU) and associated costs in adults with SLE in the USA. Claims data from the Merative MarketScan Commercial and Medicare Supplemental Database between 2011 and 2019 were used to identify patients with incident SLE. The date of first claim with SLE was defined as the index date, with a 24-month pre-index and ≥24-month post-index period. Descriptive statistics were used to evaluate patient demographics and baseline clinical characteristics, treatment patterns, adherence, HCRU and cost. Multivariable-adjusted logistic regression models were used to identify factors associated with transition between SOTs. Overall, 2476 patients received SLE treatment. The mean (SD) age was 46.9 (14.1) years and the mean (SD) follow-up duration was 47.8 (15.7) months. High corticosteroid use was prevalent in all SOTs (≥1 corticosteroid; average dose, 16.8-19.3 mg/day; 50%-60% patients). Antimalarials were most commonly prescribed in SOT 1 (85.7%), and immunosuppressants in SOT 2 and 3 (85.4% and 77.5%, respectively). Transition frequency from SOT 1-2 (38.4%) and SOT 2-3 (16.9%) was influenced by immunosuppressant prescription, concomitant corticosteroid use, sex, severe disease activity, non-persistence and age. Adherence was highest for biologics, followed by antimalarials and immunosuppressants. SLE-related HCRU and associated costs increased with SOT progression (mean (SD) at baseline vs SOT 3, US$19 489 (US$45 336) vs US$23 201 (US$39 628)). SLE treatment regimens with greater adherence and reduced corticosteroid use, HCRU and associated costs are needed.

S52 Corticosteroid-Free Efficacy and Safety of Ulcerative Colitis Patients Receiving Once-Daily Obefazimod in an Open-Label, 96-Week Maintenance Study Among Patients Who Were Receiving Concomitant Corticosteroids at Induction Baseline

S52 Corticosteroid-Free Efficacy and Safety of Ulcerative Colitis Patients Receiving Once-Daily Obefazimod in an Open-Label, 96-Week Maintenance Study Among Patients Who Were Receiving Concomitant Corticosteroids at Induction Baseline

Treatment Outcome of Surgery Followed By Corticosteroid Therapy For Idiopathic Granulomatous Mastitis

Introduction: Idiopathic granulomatous mastitis (IGM) is a rare, benign, and chronic inflammatory breast condition that has been shown to have radiological and clinical similarities to breast cancer. In spite of the fact that the cause of IGM is unknown, various contributing variables have been identified, such as a reaction to chemical substances like OCP, viral disorders, autoimmune diseases, and an immunological response to milk leakage from the breast lobule. Although various methods have been used for IGM treatment (such as surgical excision, steroids, methotrexate, etc), no consensus currently exists regarding the ideal method of treatment. Due to its positive response to steroid treatment, it is hypothesized that IGM is an autoimmune disease and is well responds to corticosteroid therapy. The aim of this study is to observe the treatment outcomes of surgery and corticosteroid therapy in IGM. Materials and Methods: This quasi experimental study was conducted in Department of Surgery, Khulna Medical College Hospital from 8th August 2018 to 8th August 2019. Total 30 patients were enrolled and allocated in two groups a ratio of 1:1. In group-A there were 15 patients, received surgical treatment with corticosteroid therapy and group-B, 15 patients received only surgical treatment. A wide local excision (WLE) was done in surgical procedure to remove area of diseased unhealthy tissue with a margin of normal tissue. Corticosteroid therapy was given orally in the following regimen: 8 weeks of steroid therapy with prednisolone at 0.5mg/kg/day for 4 weeks and then tapered down slowly for 4 weeks. Then subsequent follow up conducted after 2 months and after 4 months of primary treatment to observe the treatment outcomes. Statistical analysis was carried out by using the Statistical Package for Social Sciences version 23.0 for Windows (SPSS Inc., Chicago, Illinois, USA). A descriptive analysis was performed for all data. The mean values were calculated for continuous variables. The quantitative observations were indicated by frequencies and percentages. Unpaired student t-test was used to compare continuous variables. Chi-square test used to compare categorical data. A “p” value of &lt;0.05 was considered as significant. Result was presented by tabulation and graphical presentation in the form of tables, pie chart, graphs, bar diagrams, histogram &amp; charts etc. Result: Maximum numbers of patients (50.0%) were between 31-40 years age group, mean±SD age was 29.7±10.2 years. The left breast was affected in 16(53.3%) patients, right breast in 12(40.0%) patients and bilateral in 2(6.7%) patients. Included 30 patients were allocated in two groups. Among them in group-A there were 15 patients (Surgical treatment with corticosteroid therapy) and group-B, 15 patients (Surgical treatment alone). Wide local excision was performed in all patients. Concomitant corticosteroids therapy was used in selective group (group-A). Study shows that 22(73.3%) of the patients recovered completely (80.0% versus 66.7% in group-A and group-B respectively). There was a statistically significant difference (pd”0.05). Present study revealed that incidence of complications and recurrence rate was 8(26.7%) patients, among them 3(20.0%) were of group-A, while 5(33.3%) patients were group-B. Conclusions: Present study concluded that treatment outcomes of surgery, followed by corticosteroid therapy can be preferred at Idiopathic granulomatous mastitis (IGM) in the means of less early or late postoperative complication, resolution of symptoms with high accuracy rate to relief symptoms. J Dhaka Med Coll. 2023; 32(1) : 71-76

Long-term management of moderate-to-severe atopic dermatitis with lebrikizumab and concomitant topical corticosteroids: a 68-week, randomized, double-blind, placebo-controlled phase III trial in Japan (ADhere-J).

Moderate-to-severe atopic dermatitis (AD) impacts patients' quality of life (QOL). More treatment options are urgently needed to manage this chronic disease. Lebrikizumab is a monoclonal antibody that binds to IL-13, a key mediator in AD pathogenesis. In Japanese patients, lebrikizumab has been evaluated through week (W) 16 in the randomized, placebo-controlled, phase III ADhere-J study. To evaluate long-term efficacy and safety of lebrikizumab in combination with topical corticosteroids (TCS) in the ADhere-J study. Patients aged ≥12 years and weighing ≥40 kg with moderate-to-severe AD, and receiving either subcutaneous lebrikizumab 250 mg every 2 weeks (Q2W)/every 4 weeks (Q4W) or placebo during the 16-week induction period, were evaluated during the long-term maintenance period from W16 to W68. Responders achieved co-primary endpoints at W16: Investigator's Global Assessment score of 0 or 1 (IGA [0,1]) with ≥2-point improvement from baseline, and/or ≥75% improvement from baseline in Eczema Area and Severity Index (EASI 75). In this analysis, W16 responders received lebrikizumab 250 mg Q2W or Q4W combined with TCS during the maintenance period (maintenance primary population; MPP); W16 per-protocol nonresponders received lebrikizumab Q2W with TCS (maintenance escape population; MEP). Major endpoints included IGA (0,1) with ≥2-point improvement from baseline and EASI 75 through W68. Other outcomes included QOL, itch, and serum thymus and activation-regulated chemokine. At W68, 66-81% of 103 patients in the MPP and 32-38% of 168 patients in the MEP achieved IGA (0,1) with ≥2-point improvement from baseline. EASI 75 was maintained by 83-89% of patients in the MPP, while 71-80% of patients in the MEP achieved this outcome by W68. Across treatment arms, patients in the MPP tended to maintain improvements recorded at W16, while patients in the MEP steadily improved across the maintenance period. No new safety signals were reported, and most treatment-emergent adverse events were mild or moderate in severity in both populations. Safety outcomes were consistent with previous reports for lebrikizumab treatment in global studies. These results support the use of lebrikizumab in combination with TCS for moderate-to-severe AD in the Japanese population over the long term. ClinicalTrials.gov (NCT04760314).

No Impact of Concomitant Medications on Efficacy and Safety of Biologics and Small Molecules for Ulcerative Colitis

While participants with inflammatory bowel diseases (IBD) in clinical trials of biologics and small molecule drugs (henceforth, advanced therapies) frequently receive several medications concomitantly, it is unclear how they modify treatment effect. Through an individual patient data pooled analysis of ten clinical trials of advanced therapies for moderate-to-severe ulcerative colitis (UC), we assessed whether concomitant exposure to corticosteroids, immunomodulators, 5-aminosalicylates, proton pump inhibitors (PPIs), histamine receptor antagonists (H2RA), opiates, antidepressants, and antibiotics modified the effect of the intervention on treatment efficacy and safety outcomes, using modified Poisson regression model. Of 6044 patients (4280 receiving intervention, 1764 receiving placebo), several received concomitant corticosteroids (47%), immunomodulators (28%), 5-aminosalicylates (68%), PPIs (14%), H2RAs (2%), opiates (7%), antidepressants (6%), and/or antibiotics (5%). After adjusting for confounders and examining treatment efficacy of intervention vs. placebo, we observed no impact of concomitant exposure to corticosteroids (ratio of relative risk of drug vs. placebo with vs. without concomitant exposure: RRR, 0.81 [95% CI,0.63-1.06], 5-aminosalicylates (RRR, 1.04[0.78-1.39]), PPIs (RRR, 0.87 [0.61-1.22]), H2RAs (RRR, 1.72[0.97-14.29]), opiates (RRR, 0.90[0.54-1.49]), antidepressants (RRR, 1.02[0.57-1.83]), and antibiotics (RRR, 0.72[0.44-1.16]) on likelihood of clinical remission. Concomitant exposure to immunomodulators was associated with lower likelihood of achieving clinical remission (RRR, 0.73[0.55-0.97]), particularly with non-TNF antagonists. In clinical trials of advanced therapies for UC, baseline concomitant exposure to multiple commonly used class of medications does not impact treatment efficacy or safety. These findings directly inform design of regulatory clinical trials with respect to managing concomitant medications at baseline.

Etrasimod Corticosteroid-Free Efficacy, Impact of Concomitant Corticosteroids on Efficacy and Safety, and Corticosteroid-Sparing Effect in UC: Analyses of the ELEVATE UC Clinical Programme

Abstract Background Etrasimod is an oral, once-daily, selective sphingosine 1-phosphate (S1P)1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). This post hoc analysis reports efficacy and safety by baseline corticosteroid use in the ELEVATE UC clinical programme. Methods Patients with UC received etrasimod 2 mg or placebo for up to 52 weeks. Corticosteroid use was permitted; tapering was recommended from Week 12. Efficacy was assessed at Weeks 12 and 52 in ELEVATE UC 52, and Week 12 in ELEVATE UC 12, in patients in the corticosteroid (CS) and no-CS subgroups. CS-free efficacy at Week 52 was assessed in patients with baseline CS use. Results In ELEVATE UC 52 and ELEVATE UC 12, 93/289 (32.2%) and 65/238 (27.3%) patients receiving etrasimod and 42/144 (29.2%) and 34/116 (29.3%) patients receiving placebo, respectively, had concomitant CS use at baseline. In the CS and no-CS subgroups, higher proportions of patients who received etrasimod vs placebo achieved clinical remission (p &amp;lt; 0.05) in ELEVATE UC 52 at Weeks 12 (CS: 32.3% vs 16.7%; no-CS: 26.0% vs 4.9%) and 52 (CS: 31.2% vs 9.5%; no-CS: 33.2% vs 6.9%). In the CS subgroup, significantly more patients receiving etrasimod than placebo achieved CS-free clinical remission at Week 52 (31.2% vs 7.1%). No increases in infection rates were observed with baseline CS use. Safety was comparable between subgroups. Conclusions Etrasimod demonstrated efficacy in inducing and maintaining remission in both subgroups. CSfree remission was achieved in the CS subgroup. Safety was consistent, with no increase in infections.

Elective hand surgery and concomitant corticosteroid injection: Confirming increased infection risk using A national dataset

BackgroundRecent studies demonstrate a link between corticosteroid injection and surgical complications when procedures occur shortly after steroid administration. These publications focus on single procedures like carpal tunnel release. This study seeks to demonstrate how surgical site infection risk changes across thirteen common elective hand procedures when steroid injection is performed contemporaneously. MethodsThe Truven MarketScan® database identified patients who had undergone elective hand surgery between 2015 and 2016. Two cohorts were created based on the administration, or absence thereof, of contemporaneous corticosteroid injection. The primary outcome measure was infection within 30 days of surgery as measured by antibiotic prescription or repeat surgical intervention. Multivariate logistic regression was performed to assess the association between concomitant corticosteroid injections and post-operative infections while controlling for demographics and comorbidities. Results149,689 patients underwent elective hand surgery. 6104 (4.1 %) received concomitant corticosteroid injection and 14,070 (9.4 %) received post-operative antibiotics or underwent secondary surgical intervention for infection. Treatment for post-operative infection was significantly higher in the corticosteroid group (10.2 % versus 9.3 %; p = 0.02) driven by difference in severe infection requiring surgical intervention (3.7 % versus 3.1 %; p = 0.03). This finding persisted when controlling for demographics and comorbidities with adjusted OR of 1.10 (CI 1.01–1.20) for all infections and 1.16 (CI 1.01–1.33) for severe infections. DiscussionThese results support prior findings that patients undergoing concurrent steroid injections and surgery have increased rates of infectious complications though the absolute risk remains small. Limitations of the database preclude further investigation into the details of each procedure (e.g. ipsilateral vs contralateral injection, peri-operative antibiotics) which may impact infection rates. ConclusionsConcomitant steroid injection with elective hand surgery may increase the risk of postoperative infection, particularly severe infection. However, that relative increase lies between 1 and 33 percent and should be weighed against the benefit from intraoperative corticosteroid administration.

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.

Prior herpes zoster occurrence and high-dose corticosteroids increase herpes zoster risk in rheumatoid arthritis patients receiving janus kinase inhibitors in a retrospective and observational study.

Herpes zoster (HZ) risk is increased in rheumatoid arthritis (RA) patients receiving Janus kinase inhibitors (JAKi) therapy. Identifying and evaluating the risk factors of HZ development in patients receiving JAKi therapy would be clinically helpful. We investigated HZ's incidence rates (IR), identified the risk factors, and further assessed their influence on HZ development in RA patients undergoing JAKi therapy. We retrospectively evaluated 249 RA patients who received JAKi therapy between 2015 and 2023. Data regarding clinical characteristics, HZ reactivation, HZ vaccination status, and concomitant medication use were collected. Among 249 JAKi-treated patients, 44 developed new-onset HZ (tofacitinib, 28/142; baricitinib, 6/35; upadacitinib,10/72), with an IR of 5.11/100patient-years. Multivariate analysis revealed significant predictors of HZ development: a long JAKi exposure period, prior HZ or COVID-19 history, and concomitant high-dose corticosteroids use. The interval between JAKi initiation and HZ development was significantly shorter in patients with prior HZ history than in those without (median, 6.5months versus 33.5months, p < 0.001), suggesting "biphasic" emergence of HZ. Only one patient who had experienced an HZ episode while receiving JAKi developed recurrent HZ. None of the seventeen patients immunized with the non-live recombinant zoster vaccine developed HZ. Our JAKi-treated patients had elevated HZ risks, a class effect across different JAKi. A long exposure period, prior history of HZ or COVID-19, and concomitant high-dose corticosteroid treatment may further increase the risk. The emergence of HZ shows a biphasic pattern: early HZ development in patients with prior HZ and late development in those without. Key Points • An increased risk of HZ was observed in Taiwanese RA patients treated with JAKi, presenting as a class effect. • Patients with a long JAKi exposure period, prior history of HZ or COVID-19, and concomitant use of high-dose corticosteroids were at high risk of HZ while receiving JAKi therapy. • The interval between JAKi initiation and HZ occurrence was shorter in patients with prior HZ than in those without, showing "biphasic" emergence.

Vitamin D Metabolism Parameters and Cytokine Profile in COVID-19 Patients with Bolus Cholecalciferol Supplementation.

This study represents the next stage of the open-label randomized pilot conducted by the Almazov National Medical Research Centre. A total of 44 hospitalized patients, comparable in demographic, clinical, laboratory and instrumental baseline characteristics, with moderate/severe COVID-19 were included. All patients had similar doses of concomitant corticosteroid therapy. Twenty-two patients received 50,000 IU cholecalciferol on the first and eighth days of hospitalization. The serum 25(OH)D, 1,25(OH)2D and 28 plasma cytokines were estimated for each group initially and on the ninth day of hospitalization. Initially, there were no differences in the 1,25(OH)2D and cytokine levels in patients with vitamin D deficiency and normal 25(OH)D. Bolus cholecalciferol therapy at a total dose of 100,000 IU led to an increase in 25(OH)D levels in hospitalized patients with COVID-19, while the levels of the active metabolite (1,25(OH)2D) did not show significant differences between the groups or in its increased level over time, regardless of cholecalciferol supplementation. Furthermore, cholecalciferol supplementation at a total dose of 100,000 IU did not affect the majority of the cytokines estimated on the ninth day of hospitalization, except for the pro-inflammatory marker IL-1b, the concentration of which was lower in the group of patients without vitamin D supplementation. The 25(OH)D level was positively associated with an anti-inflammatory immune response, but cholecalciferol supplementation at a total dose of 100,000 IU did not affect the active-form vitamin D or cytokine expression levels. This fact may be explained by the impact of corticosteroid therapy, and it requires further investigation in a post-COVID-19 context.

Filgotinib induction-study baseline characteristics of patients with ulcerative colitis who achieve sustained corticosteroid-free remission: post hoc analysis of the phase 2b/3 SELECTION study.

Obtaining and maintaining corticosteroid-free remission are important goals of treatment for ulcerative colitis (UC). Characteristics associated with achieving corticosteroid-free remission were assessed in filgotinib-treated patients in SELECTION, a 58-week, phase 2b/3 trial in moderately to severely active UC. This post hoc analysis used data from filgotinib-treated patients receiving corticosteroids at maintenance baseline in SELECTION. Univariate logistic regression was performed to assess induction baseline characteristics associated with 6 months of corticosteroid-free remission at week 58, defined as clinical remission without using corticosteroids for at least 6 months. At maintenance baseline, 92 and 81 patients were receiving corticosteroids in the filgotinib 200 mg and filgotinib 100 mg groups, respectively. Age, body mass index, history of pancolitis, disease duration, fecal calprotectin levels, C-reactive protein levels, Mayo Clinic Score, concomitant corticosteroids, immunomodulators, and aminosalicylates had no statistically significant effect on the likelihood of achieving corticosteroid-free remission. Baseline characteristics associated with increased odds of corticosteroid-free remission were Mayo Clinic Endoscopic Subscore of 2 (vs. 3) in the filgotinib 200 mg and filgotinib 100 mg groups, and female (vs. male) sex, current (vs. former or never) smoking, and being biologic‑naive (vs. experienced) in the filgotinib 200 mg group. Steroid tapering can be achieved in patients with UC receiving filgotinib 200 mg independently of baseline characteristics such as clinical activity and duration of illness. However, the likelihood of achieving corticosteroid-free remission was higher among patients who were biologic-naive, current smokers, had low endoscopic inflammatory burden and who were female.

Real-world effectiveness and safety of tofacitinib for alopecia areata: A retrospective cohort study of 202 patients.

Alopecia areata (AA) is an autoimmune hair loss disorder characterised by collapse of hair follicle immune privilege and mediated by autoreactive CD8+ T lymphocytes and natural killer cells. Treatment is often unsatisfactory. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is implicated in the pathogenesis of AA and Janus Kinase inhibitor (JAKi) medications are promising emerging treatments for AA. We evaluated the safety and effectiveness of tofacitinib in a real-world setting over 18 months of treatment. A retrospective cohort study of all patients with scalp AA commenced on tofacitinib between 1 November 2016 and 31 May 2019. The primary endpoint was the percent change in Severity of Alopecia Tool (SALT) score at 18 months. Two hundred and two patients were included. After 18 months of treatment, 55.9%, 42.6% and 29.2% achieved 50%, 75% and 90% reductions in their SALT scores respectively. Increased duration of AA was a negative predictor of hair regrowth. Males and patients with baseline SALT ≥90 were slower to respond to treatment in the first 12 months. One hundred and twenty-four patients and 168 patients received concomitant systemic corticosteroids or low-dose oral minoxidil during tofacitinib therapy respectively. There were no serious adverse events. Tofacitinib was a safe and effective treatment for patients with moderate-to-severe AA. Further randomised controlled studies are needed to establish the optimal treatment regimen.

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 .

P.055 Corticosteroid dose tapering in patients with generalised myasthenia gravis on zilucoplan: Interim analysis of RAISE-XT

Background: In the Phase 3 RAISE study (NCT04115293), zilucoplan significantly improved MG-specific outcomes in patients with acetylcholine receptor autoantibody-positive generalised MG. After the first 12 weeks of the open-label extension study, RAISE-XT (NCT04225871), corticosteroid dose could be changed per the investigator’s discretion. We evaluate changes in corticosteroid dose during treatment with zilucoplan in RAISE-XT. Methods: In RAISE-XT, adults who completed the Phase 2 or RAISE studies (N=200) self-administered daily subcutaneous zilucoplan 0.3mg/kg, either continuing with zilucoplan or switching from placebo. Primary outcome was incidence of treatment-emergent adverse events (TEAEs). We assessed (post-hoc) the proportion of patients who discontinued/reduced or increased corticosteroid dose relative to double-blind baseline up to Week 60. Results: At Week 60, 30% (n=18/60) and 22% (n=12/54) of patients receiving corticosteroids in the zilucoplan and placebo-switch groups, respectively, reduced/discontinued corticosteroids (mean dose reductions: 14mg and 16mg; mean [SD] CFB in MG-ADL scores: -5.00 [3.96] and -5.67 [6.89]. 12% (n=7/60) and 7% (n=4/54) of patients in the zilucoplan and placebo-switch groups, respectively, increased corticosteroid dose (~12mg mean increase in both groups). TEAEs occurred in 188 (94.0%) patients (data cut-off: 08 September 2022). Conclusions: While receiving zilucoplan, discontinuation or dose reduction in concomitant corticosteroids was possible with maintained efficacy.