Concomitant Immunosuppression Research Articles

P1012 Systemic biologic therapies are associated with comparable safety outcomes to vedolizumab for the management of Inflammatory Bowel Disease following liver transplantation

Abstract Background Although the ‘gut-specific’ safety profile of vedolizumab may be considered advantageous in inflammatory bowel disease (IBD) patients on concomitant immunosuppression following liver transplant, the safety of vedolizumab has not been compared with ‘systemic’ biologic therapies in this context. This study aimed to compare the safety of ‘gut-specific’ and ‘systemic’ biologic therapies to manage IBD following liver transplantation (LTx). Methods A retrospective observational study of IBD patients exposed to biologic therapy following LTx was undertaken across two Australian LTx centers. The primary outcome was the incidence rate of safety events per patient-year of biologic exposure, while the secondary outcome was the impact of non-biologic immunosuppression on safety events. Safety events were defined as any documented infection whilst on biologic therapy, and were stratified accordingly to ‘gut-specific’ (vedolizumab) or ‘systemic’ (anti-TNF, ustekinumab) biologic exposure. A severe safety event was defined as one that required hospitalisation. Results Thirty-six patients were exposed to 59 (median 12 (IQR 6-27) months) biologic episodes for IBD following LTx. Most patients had co-existing primary sclerosing cholangitis (88.9%) and ulcerative colitis (72.2%) (Table 1). The cohort were collectively exposed to 44.5 and 44.4 patient-years of ‘gut-specific’ (n=27) and ‘systemic’ (anti-TNF, n=22; ustekinumab, n=10) biologic therapy, respectively. Twenty-seven (45%) biologic episodes were associated with 41 safety events a median of 8 months (IQR 4.5-13.5) following biologic initiation (Table 2A). The incidence rate of safety events were comparable between ‘gut-specific’ and ‘systemic’ biologic exposures (0.43 vs 0.50 per patient-year, p=0.79). Corticosteroid exposure at biologic initiation was the only non-biologic immunosuppressive exposure associated with more frequent severe safety events (incidence ratio 5.40 [95% CI 1.66-17.63, P<0.01]; Table 2B). Conclusion In this study of LTx recipients with IBD, incidence of safety events between those exposed to ‘gut specific’ and ‘systemic’ biologic therapies were comparable. These data suggest that choice of IBD biologic therapy should not be primarily influenced by concurrent transplant immunosuppression. However, corticosteroid co-therapy at biologic initiation may be associated with a higher incidence of severe safety events, highlighting the need to rationalise corticosteroid therapy following biologic initiation. These observations warrant validation in separate cohorts.

P0849 Real-world efficacy and safety of filgotinib in ulcerative colitis: results from the ENEIDA registry

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory disorder characterized by periods of relapse and remission. Current treatment options aim to achieve mucosal healing and sustain long-term remission, yet many patients experience treatment failure. Filgotinib (FIL), a selective JAK1 inhibitor, has emerged as a promising therapeutic agent in UC management with favorable outcomes in clinical trials. This study aimed to evaluate the real-world efficacy and safety of FIL in patients with moderate-to-severe UC. Methods We conducted a multicenter, observational, retrospective study involving adult patients with moderate-to-severe UC who were treated with FIL within the ENEIDA registry, a nationwide prospectively-maintained database. Data were collected from 28 Spanish IBD units between 12/2021 and 10/2024. Patients were eligible if they had an established diagnosis of UC, had been initiated on FIL and without previous colectomy. The primary outcome was clinical remission (partial Mayo ≤2 with no subscore >1 and no rectal bleeding) at week 12 and 52, along with its safety profile. Results A total of 91 patients were included (mean age of 37.5 years (SD 18), 63% male, and a median disease duration of 83 months [IQR, 35-148], 65% non-smokers, 15% extraintestinal manifestations). Most of them had extensive (49%) or left-sided colitis (42%). Prior exposure to anti-TNF was present in 89%, vedolizumab in 43%, and ustekinumab in 38%, with 18% also exposed to JAK inhibitors. The majority of patients had Mayo 2 or 3 endoscopic score (87%). All but 2 patients started FIL 200 mg bid (98%) and 27% received concomitant steroids or immunosuppressants (5%). Steroid-free clinical remission was 42% and 48% after 12 and 52 weeks, respectively (Figure 1). FIL persistence was 64% with median treatment duration of 6 months (IQR, 3.8-9.7). Those previously exposed to JAK inhibitors showed a 80% and 40% persistence after 12 and 52 weeks, respectively. This subgroup showed similar steroid-free clinical remission rates of 33% and 17%, respectively. Overall, hospital admission was indicated in 7% and colectomy in 1%. FIL was generally well-tolerated, with 18% of patients reporting at least one adverse event, 19% of them considered as serious, including herpes zoster infection in 2% (both vaccinated, 1 severe infection requiring FIL withdrawal), with no cardiovascular or thromboembolic events reported. Conclusion In this real-world, multicenter observational study, FIL demonstrated its efficacy in the induction and maintenance of clinical remission in patients with active UC. The real-world safety profile was consistent with previous data, with no unexpected adverse events. These findings support FIL as a valuable therapeutic option in the management of UC.

P0739 Treatment persistence, clinical, and biological outcomes following an elective switch from intravenous to subcutaneous infliximab and vedolizumab

Abstract Background Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for treating ulcerative colitis (UC) and Crohn’s disease (CD). This study reports on treatment persistence, as well as clinical, biological and pharmacological outcomes following an elective switch from maintenance intravenous (IV) to SC IFX and VDZ. Methods We conducted a single–centre, prospective, observational study from November 2021 through June 2024, enrolling stable inflammatory bowel disease (IBD) patients (based on physician global assessment) willing to switch from maintenance IV IFX or VDZ to SC treatment, and with a minimum follow-up of 34 weeks. Data were collected on patient characteristics, prior and current medications, clinical and biological activity, and pharmacokinetics. Assessments were made at time of last IV infusion, baseline (first SC injection, 4 weeks after last IV), week 8, week 34, and last follow-up. The primary objective was SC treatment persistence. Secondary objectives included change in the two-component patient reported outcome (PRO2), C-reactive protein (CRP), faecal calprotectin and serum levels (SL). Results In this study, 140 IBD patients (median age 44.2 years, 78 female, 64 UC, 76 CD) switched from IV IFX (n=59) or VDZ (n=81) to SC treatment. One hundred and fifteen patients were on standard IV dosing versus 25 patients on optimized IV dosing (19 IFX, 6 VDZ). No patient received concomitant immunosuppressants. Over a median follow-up of 20.2 (IQR 13.6-26.4) months, 83.6% of patients remained on the SC formulation, with more patients continuing on SC IFX compared to VDZ (odds ratio 2.56 [95% CI 1.12-5.88], p=0.025, Figure 1). No other baseline factors were linked to treatment persistence. The main reasons for discontinuation were disease flare and side effects (Figure 1). Seventeen patients returned to IV treatment, while six patients switched to another biologic. Median (IQR) PRO2 (for UC: 0 [0-0] at baseline, 0 [0-1] at week 8, and 0 [0-0] at week 34; for CD: 2 [0-7] at baseline, 2 [0-7] at week 8, and 0 [0-6] at week 34), CRP (1.6 [0.7-3.8] mg/L at baseline, 1.4 [0.6-3.7] mg/L at week 8, and 1.9 [0.7-5.1] mg/L at week 34), and faecal calprotectin (30 [30-112] µg/g at baseline, 37 [30-139] µg/g at week 8, and 54 [30-86] µg/g at week 34) remained stable over time. However, median (IQR) IFX and VDZ SL increased significantly over time compared to time of last IV infusion (all p<0.0001) (Table 1). Conclusion Switching from maintenance IV to SC IFX or VDZ is a viable option for stable IBD patients, though 16% experienced flare-ups or side effects after switch. Treatment discontinuation was more common with SC VDZ than IFX.

Mepolizumab efficacy and safety in patients with eosinophilic granulomatosis with polyangiitis in real practice: Data from a Spanish retrospective multicentric register from Rheumatology departments.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a type of ANCA-associated vasculitis mostly mediated by eosinophils. Mepolizumab (MPZ) reduces the absolute number of eosinophils in the peripheral blood and tissues and has proven efficacy in the maintenance of EGPA, as shown in a randomized controlled trial. The aim of this study is to describe the use of MPZ in EGPA in real clinical practice. This is a descriptive, retrospective and comparative analysis of the clinical features, course, response rates, outcomes and adverse effects of patients receiving MPZ for EGPA in thirteen Spanish Rheumatology departments. A total of 30 EGPA patients treated with MPZ were included in the analysis. Up to 19 patients needed at least one concomitant immunosuppressant. The mean follow-up was 16 months. The use of MPZ reduced the median Birmingham Vasculitis Activity Score (BVAS), as well as the mean C-reactive protein and the levels of eosinophils. In addition, the median dose of glucocorticoids (GC) required was reduced in 79.3% of the patients and was completely suspended in 57.1%. Interestingly, the median Vasculitis Damage Index (VDI) was also calculated in 27 patients (90%), and remained stable (3 [0-12] pre-MPZ and 3 [0-12] post-MPZ). None of the patients suffered severe adverse effect, local reactions or serious infections during the treatment. Our data on the real practice use of MPZ in EGPA suggests that this drug has good efficacy, is safe and reduces the dependence on glucocorticoids or even their complete withdrawal. Furthermore, it appears to prevent the organic damage progression associated with this disease.

Two Patients with Therapy-Resistant Pemphigus Vulgaris and Severe Underlying Disease Showing Good Response to a New IVIg Preparation.

Pemphigus vulgaris is a severe and often therapy-resistant bullous autoimmune disease. Standard therapy with steroids often administered together with another immunosuppressant does not respond in all patients or may not be a good therapeutic option in patients with severe underlying diseases. Intravenous immunoglobulins (IVIgs) represent a treatment alternative, often showing a rapid response which allows one to reduce concomitant immunosuppression. Here, we report on two patients with a complex disease history suffering from severe pemphigus vulgaris who received treatment with a new IVIg preparation (Yimmugo®, 2g per kg body weight every 4weeks). IVIg preparations differ regarding manufacturing process and show a varying side effect profile. Both of our patients did not experience any side effects from IVIgs and showed a significant improvement of skin and mucosal erosions. More reports on IVIgs are desirable to help in selecting the optimal preparation and dosing regarding tolerability and effectiveness for individual patients.

Management of Thrombocytopenia in SLE

Thrombocytopenia is a common manifestation of systemic lupus erythematosus (SLE) and is often associated with other haematological manifestations such as leukopenia and haemolytic anaemia. It is a poor prognostic marker and is an independent marker of mortality and morbidity. Several autoantibodies, such as anti-glycoprotein IIb/IIIa (GpIIb/IIIa), anti-GpIa/IIa, anti-GpIb/IX, anti-thrombopoietin receptor (TPO-R) and antiphospholipid antibodies, play a role in the pathogenesis of thrombocytopenia in SLE. Glucocorticoids are considered the first line in the management. However, when prescribed alone, it results in relapses and poor outcomes; therefore, guidelines recommend concomitant immunosuppressants along with glucocorticoids. The choice of concomitant immunosuppression may depend on other SLE-related manifestations. Rituximab and immunoglobulin have been used in relapsed and refractory thrombocytopenia. TPO-R agonists such as eltrombopag and romiplostim approved for chronic immune thrombocytopenia are found to be efficacious in SLE thrombocytopenia. However, TPO-R agonists are associated with a risk of thrombosis and rebound thrombocytopenia after stopping them. Therefore, an individualised approach is required when treating thrombocytopenia in SLE.

Adalimumab Autoantibodies in Uveitis Patients: Do We Need Routine Drug Monitoring?

Adalimumab, an anti-TNF-α biologic agent, has emerged as a principal treatment option for patients with non-infectious uveitis. The influence of adalimumab anti-drug antibodies (AAA) on the efficacy of adalimumab therapy is not yet fully understood. We aim to understand their clinical implications in the context of therapeutic drug monitoring and the factors contributing to the formation of these antibodies. We conducted a retrospective analysis of 114 patients with non-infectious uveitis who developed AAA while undergoing adalimumab therapy. Among the 114 AAA-positive uveitis patients, a significant correlation was observed between AAA levels and reduced adalimumab serum levels (r = -0.58, p < 0.001). The mean time to AAA detection was 2.1 years (range 0.1-11.9 years), with 45.6% of cases identified through routine testing. If AAA levels were initially low, subsequent measurements for AAA were more likely to become negative during treatment (r = 0.63, p < 0.001). Higher AAA concentrations were associated with a shorter time to detection (r = -0.27, p = 0.01) and younger age (r = -0.21, p = 0.03). There was a trend, though no significant influence, of concomitant immunosuppression with prednisolone ≤ 7.5 mg or methotrexate on antibody formation (p = 0.18). No significant difference was observed in AAA levels between uveitis subtypes. Higher AAA concentrations are associated with lower adalimumab serum levels in uveitis patients. Routine clinical testing is essential for optimal therapeutic drug monitoring to prevent early loss of effectiveness.

Macular Edema Ranibizumab v. Intravitreal anti-inflammatory Therapy (MERIT) Trial—24-week Outcomes of Uveitic Macular Edema Retreatment

PurposeEvaluation of longer-term effectiveness of three intravitreal therapies (methotrexate, ranibizumab, or dexamethasone implant) for participants enrolled in the randomized comparative effectiveness trial the Macular Edema Ranibizumab versus Intravitreal anti-inflammatory Therapy (MERIT) Trial followed for24 weeks. DesignMulticenter randomized controlled clinical trial with masked evaluation of retinal thickness and visual acuity. ParticipantsPatients with persistent or recurrent uveitic macular edema. MethodsParticipants from 33 centers were randomized 1:1:1 (stratified by presence or absence of concomitant systemic immunosuppression for uveitis) to receive a sequence of intravitreal treatments with dexamethasone implant, methotrexate or ranibizumab. Participants with bilateral macular edema received the same treatment bilaterally. During 24 weeks’ follow-up, non-assigned treatments were permitted beginning from12 weeks for those meeting retreatment criteria. Main Outcome MeasuresCentral subfield thickness change (CST) from baseline optical coherence tomography (OCT) measurement was the main outcome. Secondary outcomes included change in mean standard letters from baseline best-corrected visual acuity (BCVA). Analyses were conducted according to two principles: 1) “As-Assigned” in which outcomes were analyzed according to their original randomized treatment; and 2) a supplementary “Censored” analysis in which data were excluded after an eye received non-assigned treatment. ResultsAmong 194 enrolled participants (225 eligible eyes), 177 (207 eyes) completed 24 weeks’ follow-up. Eyes assigned to methotrexate (55%) and ranibizumab (37%) more frequently received non-assigned treatments (88% dexamethasone implant or intravitreal corticosteroid injection) compared to dexamethasone (7%). In the As-Assigned analysis, dexamethasone had superior improvement in macular edema compared to ranibizumab (CST: 34% vs 19%, p=0.01) but not compared to methotrexate (CST: 31%, p=0.59) after being superior to both other regimens at 12 weeks. However, in the Censored analysis, only dexamethasone was associated with improvements in macular edema [CST: 34% vs 8% (p<0.001) and 5% (p<0.001)] and BCVA improvement >5 letters compared to methotrexate and ranibizumab, respectively. Dexamethasone more often was associated with IOP elevations ≥ 24 mmHg (32%) and ≥30 mmHg (10%). ConclusionsDexamethasone was more effective that methotrexate and ranibizumab for the treatment of persistent or recurrent uveitic macular edema through 24 weeks, with manageable side effects.

Candidemia in an Orthopedic Patient Detected Coincidentally by Peripheral Blood Smear.

An elderly male, with a recent COVID-19 infection and cardiovascular comorbidities, experienced a prolonged hospitalization due to a periprosthetic joint infection (PJI) and bacteremia, post hip hemiarthroplasty. Despite the initial clinical improvement while on targeted antimicrobial therapy, the patient later developed a low-grade fever and signs of myelosuppression. In the May-Grünwald-Giemsa stain of peripheral blood smear (PBS), pseudohyphae among red blood cells (RBCs) and phagocytosed blastospores in neutrophils and monocytes were detected, indicating candidemia rather than contamination of the stain. Echinocandin treatment was immediately initiated, and Candida albicans was identified from the blood culture, using multiplex polymerase chain reaction (PCR). Despite the early initiation of antifungal therapy and the removal of the central venous line (CVL), the patient passed away within 24 h. Candidemia is a leading cause of nosocomial bloodstream infections with high morbidity and mortality and is associated with multiple risk factors including surgery, CVLs, prolonged hospitalization, concomitant bacterial infection, broad-spectrum antibiotics, and immunosuppression. Isolation from blood cultures remains the gold standard for diagnosing candidemia. Detection of candidemia by PBS is extremely rare, requires an experienced microscopist, and is considered to be an emergency. Clinical suspicion, early laboratory identification, and immediate clinician notification are crucial for prompt antifungal treatment.

Prognostic value of soluble programmed death-1 and soluble programmed death ligand-1 in severe traumatic brain injury patients

Patients with traumatic brain injury (TBI) frequently exhibit concomitant immunosuppression. In this study, we evaluated the predictive values of soluble programmed death-1 (sPD-1) and soluble programmed death ligand-1 (sPD-L1) in patients with severe TBI. Peripheral blood sPD-1 and sPD-L1 levels were measured within 48 h of patient admission. A total of 20 healthy volunteers and 82 patients were enrolled in this study. The levels of sPD-1 and sPD-L1 were upregulated in patients with severe TBI (P < 0.001). They were significantly increased in the post-TBI severe pneumonia group and among non-survivors (P < 0.001). The area under the curves (AUCs) for sPD-1 and sPD-L1 levels to predict severe pneumonia were 0.714 and 0.696, respectively, and the AUCs to predict mortality were 0.758 and 0.735. The levels of sPD-1 and sPD-L1 are correlated with the GCS scores at admission, APACHE II scores, length of MV, and time elapsed to mortality. The levels of sPD-1 and sPD-L1 emerged as independent predictive factors for severe pneumonia and mortality. This study demonstrates that upregulation of sPD-1 and sPD-L1 in severe TBI patients is significantly associated with severe pneumonia and mortality, suggesting their potential as predictive biomarkers for these outcomes.

Moving from Insulin Substitution to the Treatment of the Underlying Autoimmune Disease in Type 1 Diabetes.

Currently, a paradigm change occurs in type 1 diabetes from insulin substitution to the treatment of the underlying autoimmune disease. Teplizumab, a humanized monoclonal anti-CD3 antibody, is the first FDA-approved disease-modifying treatment of preclinical stage 2 diabetes. Research of drugs like golimumab, a monoclonal antibody specific for TNF alpha, baricitinib, a tyrosine kinase inhibitor, or frexalimab, a monoclonal antibody against the CD40 ligand, is still ongoing. Repurposing drugs that have been used in other indications like the calcium channel blocker verapamil, antithymocyte globulin (ATG), an antibody preparation used in solid organ transplantation, glucagon-like peptide-1 agonists utilized in type 2 diabetes and obesity, or the antiviral drugs pleconaril and ribavirin have shown positive effects in preserving beta-cell function. While new therapies to halt autoimmunity and restore beta cells in stages one to three are being developed, replacing beta-cell function via inducible pluripotent stem cells have shown glucose control and insulin independence in long-standing type 1 diabetes, albeit with concomitant immunosuppression. Multicenter multinational initiatives developing a clinical trial network like INNODIA or a research platform with the goal of stopping type 1 diabetes in its early stages like EDENT1FI will be instrumental to study these new strategies.

Initiation of belimumab with higher daily prednisolone is effective for rapid glucocorticoid reduction: A 96-week retrospective study.

For appropriate glucocorticoid (GC) reduction, we investigated the optimal strategy including baseline factors that could reduce GC more than 50% with 96weeks of belimumab. This is a retrospective cohort study of Kakogawa Central City hospital from 2019 to 2023. We identified SLE patients who were receiving 200mg of belimumab weekly by subcutaneous injection for 96 weeks. The background at baseline, trends in clinical indicators, and factors involved in GC reduction were statistically analyzed. Finally, univariate and multivariate logistic analyses were carried out to identify baseline factors associated ≥50% GC reduction at 96weeks. Forty-seven patients were enrolled, with a median daily prednisolone of 5mg. Almost 90% of them received concomitant immunosuppressants and/or hydroxychloroquine. Serological indices, daily GC dose, and SLEDAI-2K scores showed significant improvement in 96weeks. At baseline, a significant negative correlation has been shown between the daily dose of GC and the duration from onset or last flare, as well as C4 levels. At 96weeks, GC reduction rate and SLEDAI-2K scores were negatively correlated with duration from onset or last flare to initiation of belimumab. Mycophenolate mofetil use was significantly frequent in patients with lupus nephritis (LN), which also correlated with the frequency of past flares. In addition, LN presence was associated with higher SLEDAI-2K scores at 96weeks, and baseline SLEDAI-2K ≥10 was associated with significantly higher GC dose at 96weeks. Univariate analysis of the factor contributing to achieving ≥50% GC reduction at 96weeks has pointed shorter disease duration and higher daily GC dose at baseline as significant variables. Finally, we performed a multivariate analysis by combining above two items with age, which extracted the higher daily GC dose at baseline as a significant variable (OR (95% CI) 1.25 (1.00 to 1.56), p = .047). Our study showed that a delay in belimumab initiation led to higher SLEDAI-2K score and difficulty in achieving a 50% GC reduction at 96weeks. Since GC-related adverse events increase with long-term administration of GC though with small daily doses, we proposed here that belimumab should be started in combination with higher daily prednisolone.

COVID-19 prophylaxis, diagnostics, and treatment in patients with rheumatic diseases. The Polish experts panel opinion.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves, infection management in vulnerable populations requires formalized guidance. Although low-virulence variants of SARS-CoV-2 remain predominant, they pose an increased risk of severe illness in adults with rheumatic and musculoskeletal diseases (RMDs). Several disease-specific (chronic long-grade inflammation, concomitant immunosuppression) and individual (advanced age, multimorbidity, pregnancy, vaccination status) factors contribute to excess risk in RMD populations. Various post-COVID-19 manifestations are also increasingly reported and appear more commonly than in the general population. At a pathogenetic level, complex interplay involving innate and acquired immune dysregulation, viral persistence, and genetic predisposition shapes a unique susceptibility profile. Moreover, incident cases of SARS-CoV-2 infection as a trigger factor for the development of autoimmune conditions have been reported. Vaccination remains a key preventive strategy, and encouraging active education and awareness will be crucial for rheumatologists in the upcoming years. In patients with RMDs, COVID-19 vaccines' benefits outweigh the risks. Derivation of specialized diagnostic and therapeutic protocols within a comprehensive COVID-19 care plan represents an ideal scenario for healthcare system organization. Vigilance for symptoms of infection and rapid diagnosis are key for introducing antiviral treatment in patients with RMDs in a timely manner. This review provides updated guidance on optimal immunization, diagnosis, and antiviral treatment strategies.

Real-world management of patients with neuromyelitis optica spectrum disorder using satralizumab: Results from a Japanese claims database

BackgroundSatralizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has been approved globally for the treatment of neuromyelitis optica spectrum disorder (NMOSD), based on positive results from two randomized, double-blind, phase 3 studies: SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279). There remains an unmet need to understand the real-world management of NMOSD, especially in patients undergoing tapering of concomitant therapy. We examined real-world treatment patterns, including concomitant glucocorticoids and immunosuppressants, and relapse in satralizumab-treated patients with NMOSD, using a Japanese administrative hospital claims database. MethodsWe used retrospective data from the Medical Data Vision hospital-based administrative claims database. The index date was the date of first satralizumab prescription and the study period was set between August 2018 and March 2022. Patients were included in the overall population if they had a first prescription for satralizumab between August 2020 and March 2022, an International Classification of Disease, Version10 code of G36.0 prior to March 2022, and were observable for ≥90 days prior to the index date. The primary endpoint was the percentage of patients with relapse-free reduction of oral glucocorticoids to 0 mg/day at 360 days of continued satralizumab treatment. Secondary endpoints included time to relapse, number of relapses after the index date while being on continuous satralizumab treatment, annualized relapse rate before and after the index date, and concomitant medication use. Relapse and dose reduction were identified using definition specifically developed for this study. ResultsOf the 131 patients included in the overall population, most were female (90.8 %), aged 18–65 years (75.6 %), and were prescribed oral glucocorticoids (93.1 %). Azathioprine (19.1 %) and tacrolimus, a calcineurin inhibitor (18.3 %), were the most common immunosuppressants at index date. Six (4.6 %) patients had a history of biologic use (tocilizumab, 1 [0.8 %]; eculizumab, 5 [3.8 %]). Among 111 patients observable for 360 days pre-index, there were 0.6 ± 0.8 (mean ± SD) relapses during 360 days before the index date. The median (interquartile range) duration of satralizumab exposure was 197.0 (57.0–351.0) days. Most (125/131; 95.4 %) patients were relapse-free post-index; 6 (4.6 %) patients relapsed within 90 days after the index date, of which 2 had the first relapse within 7 days after the index date. Among 21 patients with 360-day follow-up, 6 (28.6 %) patients were on 0 mg/day dose of glucocorticoid prescription without relapse 360 days post-index. Of these 6 patients, 2 had no prescription of oral glucocorticoids at the index date and remained glucocorticoid- and relapse-free 360 days after the index date. ConclusionThese real-world data support the phase 3 clinical trials. Our results, over a median duration of satralizumab exposure of 197.0 days, showed that a majority (125/131, 95.4 %) of patients were relapse-free after initiating satralizumab treatment. The number of glucocorticoid-free patients without relapse increased over time under continuous satralizumab prescription. Further studies are needed to confirm if satralizumab can be used as a potential immunosuppressant- and glucocorticoid-sparing agent.

Infliximab is an effective option in patients with ulcerative colitis previously exposed to full subcutaneous anti-TNF agent: Results from a real-world multicenter study

BackgroundData on infliximab efficacy in bio-exposed patients with ulcerative colitis (UC) are limited. AimsTo evaluate infliximab effectiveness and its predictors in UC patients with prior exposure to subcutaneous (SC) anti-TNF agent. MethodsIn this multicenter retrospective study (8 centers), we included all consecutive UC patients with prior exposure to subcutaneous anti-TNF, starting infliximab for symptomatic UC, excluding acute severe colitis. Corticosteroid-free clinical remission (CFREM) was assessed at week 14 (W14) and W52 while endoscopic improvement (CFREM + endoscopic Mayo score≤1) was evaluated at W14. ResultsOverall, 104 patients were included (pancolitis=54.8%, primary failure to subcutaneous anti-TNF=57.4%, concomitant immunosuppressant=53.8%, median partial Mayo score at baseline=7[5–8]). The rate of CFREM was 33.6% (35/104) at W14 and 40.4% (42/104) at W52. At W14, endoscopic improvement was achieved in 29.8%(31/104). In multivariable analysis, concomitant immunosuppressant was associated with higher rate of CFREM at W14(OR=2.83[1.06–7.54], p = 0.037) and W52(OR=2.68[1.16–6.22];p = 0.021), while primary failure to a previous subcutaneous anti-TNF agent led to lower rate of CFREM at W14 (OR=0.37[0.14–0.98], p = 0.046). After a median follow-up of 20.9 months[11.7–33.7]), 50.0%(52/104) patients had discontinued infliximab. ConclusionInfliximab is an effective option in UC patients previously exposed to prior subcutaneous anti-TNF agent and should be used with concomitant immunosuppressant.

EFFICACY, SAFETY AND IMMUNOGENICITY OF SUBCUTANEOUS INFLIXIMAB (CT-P13 SC) MONOTHERAPY VERSUS COMBINATION THERAPY WITH IMMUNOSUPPRESSANTS – POST HOC ANALYSIS OF LIBERTY-CD AND LIBERTY-UC STUDY

Abstract INTRODUCTION CT-P13 subcutaneous (SC) infliximab formulation demonstrated superiority over placebo in maintenance therapy in Crohn's disease (CD) and Ulcerative Colitis (UC) patients in two parallel 54 weeks studies (LIBERTY-CD and LIBERTY-UC). We performed a post-hoc subgroup analysis comparing patients treated with CT-P13 SC with and without combination immunosuppressants (IS) at baseline in CD and UC. AIMS &amp; METHODS Patients with moderately to severely active CD and UC who responded at W10 to CT-P13 intravenous infliximab 5mg/kg (Weeks 0, 2 and 6) were randomized (2:1) to receive CT-P13 SC 120 mg (CT-P13 SC) or placebo every 2 weeks until W54 as maintenance therapy. IS (azathioprine [AZA], 6-mercaptopurine [6-MP], or methotrexate [MTX]) were allowed if patients maintained stable doses at least 8 weeks prior to W0, and stable doses were maintained up to W54. RESULTS 231 CD and 294 UC patients were randomized to receive CT-P13 SC maintenance therapy. Among them, 71 (30.7%) and 65 (22.1%) patients received CT-P13 SC with IS in CD and UC, respectively (In CD; 63, 4 and 4 patients of AZA, 6-MP, MTX, respectively, In UC; 63, 2 and 0 patients of AZA, 6-MP, MTX, respectively). There were no meaningful differences in efficacy outcomes at Week 54 by CT-P13 concentration tertiles at Week 54 between monotherapy and combination therapy groups in both studies (Table 1). In combined analysis of CD and UC patients, no statistically significant differences were seen in safety profile between monotherapy and combination therapy groups in the maintenance period except for infection rate (Table 2). In combined analysis of CD and UC patients, rate of anti-drug antibody [ADA] positive conversion up to W54 was statistically lower in combination therapy group (70.2% monotherapy vs 47.8% combination therapy [p&amp;lt;0.0001]). CONCLUSION No meaningful differences in efficacy outcomes at W54 were observed between monotherapy and combination therapy of CT-P13 SC in CD and UC patients. Concomitant IS use was associated with less ADA formation, whereas more infections are seen for combination therapy during maintenance period in CD and UC patients. The overall safety profile during maintenance period was otherwise comparable between monotherapy and combination therapy in CD and UC patients. This post-hoc analysis suggests limited benefit of concomitant IS with CT-P13 SC but a higher infection risk. Notably, patients were not randomized according to IS use nor were the studies ‘powered’ to demonstrate differences. Proportion of patients achieving efficacy outcomes at W54 by tertile of Serum concentrations of Infliximab (ng/mL) at W54 (Pharmacokinetic population) Safety results in maintenance period (Safety population)

P686 Comparison between therapeutic sequences starting with IV induction-biologic versus SC-induction biologic in bionaïve-patients with ulcerative colitis: results from the APPETISER study

Abstract Background Recent data suggest that infliximab and vedolizumab would be more effective than subcutaneous anti -TNF as 1st line-biologic, leading therapeutic sequencing challenging. We compared the effectiveness of a strategy starting with a first-line bologic with IV induction (IFX or VDZ = IV group) compared to a biologic with SC induction (adalimumab or golimumab = SC group) to induce and maintain steroid-free clinical remission during the first 24 months. Methods From a database of IBD referral center, all consecutive UC patients ≥ 18 years-old who started a first line of biologic (IFX, VDZ, ADAor GLM) for active UC with follow-up &amp;gt; 6 months were included. Prior colectomy or severe acute colitis were excluded. The primary endpoint was remission defined according to PRO2 (PRO2-remission) as the absence of bleeding, normalization of transit (Mayo stool frequency subscore = 0) and no steroid. PRO2-remission was defined as a binary criterion each month (the statistical unit being the month and not the patient). The secondary endpoints concerned the analysis by patient and were CFREM (partial Mayo score ≤ 2 without steroid) and endoscopic remission (CFREM + score Endoscopic Mayo ≤ 1) at week 12 . All comparisons were adjusted using propensity scores on potential confounders. Analysis by month was performed using mixed models to account for repeated data. Results Overall, 130 patients were included including 60 patients in the IV group (IFX= 50 and VDZ= 10) and 70 in the SC group (ADA= 48 and GLM= 22). The populations had similar characteristics at baseline apart from concomitant immunosuppressant more frequent in IV group (55.9% vs 21.7%). 2nd line treatment was started in 26.7% of patients in IV group (ADA in 48.8%, VDZ 25.5% and ustekinumab 18.8%) and 87.1% of patients in SC group (IFX in 54.1%, VDZ 31.1%). After adjustment, the rate of CFREM at week 12 was significantly higher in the IV arm (70.8%) than in the SC arm (33.0%) (p &amp;lt; 0.001). The rate of endoscopic remission at W12 was 22.1% and 10.0% in the IV and SC arms, respectively (p =0.18). In this study, 3350 months were analyzed (1180 in the IV arm and 1175 in the SC arm). The percentage of months spent in PRO2-CFREM in the first 24 months (primary endpoint) was greater in the IV arm than in the SC arm (74.2% vs 46.6%; p&amp;lt;0.001). The percentage of months spent in CFREM was higher in the IV arm in the first 6 months (60.4% vs 18.9%), but also between M7 and M12 (73.1% vs 38.6%), M13 and M18 (79.9% vs 57.0%) or M19 and M24 (83.3% vs 64.6%) (p &amp;lt; 0.001 for all comparisons). Conclusion A therapeutic sequence starting with IV induction biologic (IFX or VDZ) was more effective than starting with a SC induction anti-TNF (ADA and GLM ) to induce and maintain remission at short and long-term in UC.

OP37 Effect of the HLA-DQA1*05 allele on the efficacy of ustekinumab in patients with Crohn's Disease. Multicenter study based on the ENEIDA registry of GETECCU

Abstract Background HLA-DQA1*05 carriage is associated with the development of anti-drug antibodies and loss of response (LOR) to tumour necrosis factor antagonists (anti-TNF) in patients with inflammatory bowel diseases (IBD)1. Ustekinumab has shown very low rates of immunogenicity and presumably will not be affected by this risk. Identifying patients at high risk of treatment failure would be important when selecting therapy for IBD. The objective of this analysis was to investigate the relationship between the HLA- QA1*05 allele and ustekinumab on development of LOR and drug persistency. Methods This is a retrospective cohort study from a prospectively maintained ENEIDA registry. LOR was defined as recurrence or worsening of IBD related symptoms that required a change or intensification in treatment, hospitalization or surgery. Independent predictors of LOR were identified using univariate and multivariable Cox proportional hazard regression. The HLA-DQA1*05 allele was determined from a saliva sample (kit OGD-600 de DNA Genotek Oragene) and DNA extraction with the Maxwell® RSC-Stabilized Saliva DNA kits. Results 204 patients with Crohn's disease were included. Previous exposure to biological drugs was 96% (61% ≥2 biological drugs). Basal faecal calprotectin levels were 907±970μg/g and PCR levels 16.2±25 mg/dL. The median follow-up was 417±154 days. During this period, 25%, 16% and 13% of the patients required drug intensification, hospitalization or surgery, respectively. 43% of the patients included were carriers of one or two copies of the HLA-DQA1*05 allele. The presence/absence of this allele was not associated with LOR to ustekinumab (20% vs 16%, p = ns) nor with drug withdrawal (11% vs 6%, p = ns). In the multivariate analysis (COX regression), only the number of previous biological drugs was associated with ustekinumab persistency. Conclusion The presence of the HLA-DQA1*05 allele is not related to LOR or persistency of ustekinumab treatment. First-line treatment with ustekinumab rather than anti-TNF agents may be considered in HLA-DQA1*05-positive patients, particularly when the use of a concomitant immunosuppressant is contraindicated. 1. Sazonovs A, Kennedy NA, Moutsianas L, Heap GA, Rice DL, Reppell M, Bewshea CM, et al. PANTS Consortium. HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn's Disease. Gastroenterology. 2020 Jan;158(1):189-199.

Efficacy and safety of tocilizumab treatment in refractory MOG-IgG related optic neuritis.

Myelin oligodendrocyte glycoprotein (MOG) IgG related optic neuritis (ON) which manifests as recurrent episodes and severe visual impairment remains a challenging issue in relapse prevention. Tocilizumab (TCZ), a human monoclonal antibody against IL-6R, may be an alternative treatment for the prevention of relapse in refractory MOG-ON patients. To investigate the efficacy and safety of Tocilizumab (TCZ) in patients with recurrent myelin oligodendrocyte glycoprotein IgG related optic neuritis (MOG-ON). We conducted an open-label, single-arm, nonrandomized, uncontrolled clinical trial at a tertiary neuro-ophthalmology center between April 1, 2021, and April 1, 2022. Participants with relapsed MOG-ON, whose disease had been resistant to previous immunotherapies, received tocilizumab as monotherapy or as an add-on therapy and were followed up for at least 12 months. Annual recurrence rate (ARR), best corrected visual acuity (BCVA), and adverse events were recorded for analyses. Ten patients (7 females and 3 males) with relapsed MOG-ON were included with a mean (SD) ages of 28.6 (20.5) years old at disease onset and 30.9 (19.7) years at first TCZ administration, with a mean disease duration of 26.6 (11.3) months. Seven (70%) patients remained relapse-free, and the median (range) ARR dropped significantly from 1.9 (0.4-3.5) to 0.0 (0-4.0) during TCZ treatment (p = 0.006). Three patients experienced a relapse of ON at 2, 3, and 7 months after TCZ therapy. The median BCVA improved from 2.7 (2.0-3.0) logMAR at the nadir to 0.2 (0-2.0) logMAR at the last follow-up. Adverse effects included transient diarrhea (n = 1) and upper respiratory infection (n = 1). This study supports that Tocilizumab therapy, with or without concomitant immunosuppression, is safe and effective in reducing relapses in MOG-ON patients who have failed immunosuppressive therapy or targeted B-cell therapy. This trial is registered with the Chinese Clinical Trial Registry, number ChiCTR2100045273. (URL: https://www.chictr.org.cn/showproj.html?proj=124810).

Risk factors for renal dysfunction after isolated intestinal transplantation.

Kidney dysfunction is a known complication of intestinal transplantation; however, the rate of development and risk factors for chronic kidney disease (CKD) remain poorly defined. This was a single-center retrospective review of isolated adult intestinal allograft recipients from 2011 to 2019. Patients who died or experienced graft loss within 1-year or had a prior transplant were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation at 0-, 6- and 12-months post-transplant, and multivariable linear regression was performed to identify variables associated with adjusted eGFR at 1-year. Independent variables included age, ethnicity, BMI, history of diabetes/hypertension, vasopressor use, TPN and stoma days, urinary or bloodstream infections, intravenous contrast exposure, rejection, concomitant immunosuppression, and time above the therapeutic range of tacrolimus. Variables with a p<.1 in univariate analysis were considered for multivariable modeling. Thirty-three patients were included with a mean age of 43.9±13.0. A mean 42.3% decline in eGFR was observed at 1-year post-transplant, with 15.2% of patients developing new stage 4/5 CKD. Factors associated with a greater decline in adjusted eGFR in the univariate model included increasing age, decreased BMI, stoma days, and vasopressor use. In the adjusted multivariable model patient age (β=-.77, p<.01) and stoma days (β=-.06, p<.01) remained significant. Tacrolimus and sirolimus exposure were not associated with decline in eGFR at 1 year. Renal dysfunction is common following intestinal transplantation. The need for stoma creation should be carefully considered, and reversal should be performed when feasible for renal protection.