Concomitant Immunosuppression Research Articles

Efficacy and safety of obinutuzumab in systemic lupus erythematosus patients with secondary non-response to rituximab.

Secondary inefficacy with infusion reactions and anti-drug antibodies (secondary non-depletion nonresponse, 2NDNR) occurs in 14% of SLE patients receiving repeated rituximab courses. We evaluated baseline clinical characteristics, efficacy and safety of obinutuzumab, a next-generation humanized type-2 anti-CD20 antibody licensed for haematological malignancies in SLE patients with 2NDNR to rituximab. We collated data from SLE patients receiving obinutuzumab for secondary non-response to rituximab in BILAG centres. Disease activity was assessed using BILAG-2004, SLEDAI-2K and serology before, and 6 months after, obinutuzumab 2× 1000 mg infusions alongside methylprednisolone 100 mg. All nine patients included in the study received obinutuzumab with concomitant oral immunosuppression. At 6 months post-obinutuzumab, there were significant reductions in median SLEDAI-2K from 12 to 6 (P = 0.014) and total BILAG-2004 score from 21 to 2 (P = 0.009). Complement C3 and dsDNA titres improved significantly (both P = 0.04). Numerical, but not statistically significant improvements were seen in C4 levels. Of 8/9 patients receiving concomitant oral prednisolone at baseline (all >10 mg/day), 5/8 had their dose reduced at 6 months. Four of nine patients were on 5 mg/day and were in Lupus Low Disease Activity State following obinutuzumab. After obinutuzumab, 6/9 patients with peripheral B cell data achieved complete depletion, including 4/4 assessed with highly sensitive assays. Of the nine patients, one obinutuzumab non-responder required CYC therapy. One unvaccinated patient died from COVID-19. Obinutuzumab appears to be effective and steroid-sparing in renal and non-renal SLE patients with secondary non-response to rituximab. These patients have severe disease with few treatment options but given responsiveness to B cell depletion, switching to humanized type-2 anti-CD20 therapy is a logical approach.

Stringent screening strategy significantly reduces reactivation rates of tuberculosis in patients with inflammatory bowel disease on anti-TNF therapy in tuberculosis endemic region.

Anti-tumor necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to an increased risk of tuberculosis (TB) reactivation despite latent tuberculosis (LTB) screening, especially in TB endemic regions. We evaluated the effect of stringent screening strategy and LTB prophylaxis on TB reactivation. We performed an ambispective comparison between patients who received anti-TNF therapy after January 2019 (late cohort) and between Jan 2005 and Jan 2019 (early cohort). Late cohort patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, chest X-ray, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy. One hundred seventy-one patients (63: ulcerative colitis/108: Crohn's disease, mean age diagnosis: 28.5±13.4years, 60% males, median follow-up duration after anti-TNF: 33months [interquartile range: 23-57months]) were included. Among the 112 in the early cohort, 29 (26%) underwent complete TB screening, 22 (19.6%) had LTB, 10 (9%) received chemoprophylaxis, and 19 (17%) developed TB. In comparison, in the late cohort, 100% of patients underwent complete TB screening, 26 (44%) had LTB, 23 (39%) received chemoprophylaxis, and only 1(1.7%) developed TB (p<0.01). On survival analysis, patients in early cohort had a higher probability of TB reactivation compared with the late cohort (HR: 14.52 (95% CI: 1.90-110.61 [p=0.01]) after adjusting for gender, age at anti-TNF initiation, concomitant immunosuppression, anti-TNF doses, and therapy escalation. The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.

Emerging Evidence and Treatment Perspectives from Randomized Clinical Trials in Systemic Sclerosis: Focus on Interstitial Lung Disease.

Systemic sclerosis (SSc) is a complex rare autoimmune disease with heterogeneous clinical manifestations. Currently, interstitial lung disease (ILD) and cardiac involvement (including pulmonary arterial hypertension) are recognized as the leading causes of SSc-associated mortality. New molecular targets have been discovered and phase II and phase III clinical trials published in the last 5 years on SSc-ILD will be discussed in this review. Details on the study design; the drug tested and its dose; the inclusion and exclusion criteria of the study; the concomitant immunosuppression; the outcomes and the duration of the study were reviewed. The two most common drugs used for the treatment of SSc-ILD are cyclophosphamide and mycophenolate mofetil, both supported by randomized controlled trials. Additional drugs, such as nintedanib and tocilizumab, have been approved to slow pulmonary function decline in SSc-ILD. In this review, we discuss the therapeutic alternatives for SSc management, offering the option to customize the design of future studies to stratify SSc patients and provide a patient-specific treatment according to the new emerging pathogenic features of SSc-ILD.

Response to Vaccines in Patients with Immune-Mediated Inflammatory Diseases: A Narrative Review.

Patients with immune-mediated inflammatory diseases (IMIDs), such as rheumatoid arthritis and inflammatory bowel disease, are at increased risk of infection. International guidelines recommend vaccination to limit this risk of infection, although live attenuated vaccines are contraindicated once immunosuppressive therapy has begun. Biologic therapies used to treat IMIDs target the immune system to stop chronic pathogenic process but may also attenuate the protective immune response to vaccines. Here, we review the current knowledge regarding vaccine responses in IMID patients receiving treatment with biologic therapies, with a focus on the interleukin (IL)-12/23 inhibitors. B cell-depleting therapies, such as rituximab, strongly impair vaccines immunogenicity, and tumor necrosis factor (TNF) inhibitors and the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) fusion protein abatacept are also associated with attenuated antibody responses, which are further diminished in patients taking concomitant immunosuppressants. On the other hand, integrin, IL-6, IL-12/23, IL-17, and B-cell activating factor (BAFF) inhibitors do not appear to affect the immune response to several vaccines evaluated. Importantly, treatment with biologic therapies in IMID patients is not associated with an increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or developing severe disease. However, the efficacy of SARS-CoV-2 vaccines on IMID patients may be reduced compared with healthy individuals. The impact of biologic therapies on the response to SARS-CoV-2 vaccines seems to replicate what has been described for other vaccines. SARS-CoV-2 vaccination appears to be safe and well tolerated in IMID patients. Attenuated but, in general, still protective responses to SARS-CoV-2 vaccination in the context of certain therapies warrant current recommendations for a third primary dose in IMID patients treated with immunosuppressive drugs.

Duration of prednisone treatment before development of Pneumocystis jirovecii pneumonia in patients with vasculitis: A case series.

Optimal timing for Pneumocystis jirovecii pneumonia (PCP) prophylaxis among patients with vasculitis is not clear. We set out to characterize the clinical presentation and duration of prednisone use before the development of PCP among these patients. All patients with PCP at The Ottawa Hospital (TOH) between 2006 and 2017 were identified. Using TOH data repositories, the following data were extracted: prednisone dosage, treatment duration, other immunosuppressive medications, PCP prophylaxis, PCP treatment, and death. Data were reported as median and range or as mean and standard deviation. We identified seven patients (5 men, 2 women) with biopsy-proven vasculitis who developed PCP: six with anti-neutrophil cytoplasmic antibody-associated vasculitis and one with giant cell arteritis. None of the patients were on PCP prophylaxis. The most common symptoms on presentation were cough and dyspnea. At diagnosis, the median lymphocyte count was 0.30 × 109/L (range 0.03-2.10), creatinine was 186 µmol/L (range 78-359), and lactate dehydrogenase was 471 U/L (range 301-1032). All patients were on prednisone at time of PCP diagnosis, with six on doses of ≥20 mg/day for at least 12 weeks. All but one patient were on additional immunosuppressants, with cyclophosphamide being the most common agent for five of the seven patients. Four (57%) required intensive care unit admission, and two (29%) died secondary to complications of PCP. PCP is a severe and often fatal opportunistic infection among immunocompromised patients with vasculitis. Frequent evaluation of the need for prophylaxis is required for patients who remain on high-dose steroids and concomitant immunosuppressants.

P400 Evolution of clinical and pharmacological parameters after switching from intra-venous to subcutaneous infliximab in patients with inflammatory bowel disease: the REMSWITCH study

Abstract Background Owing to similar efficacy, switching from intravenous (IV) to subcutaneous (SC) infliximab (IFX) is an attractive option, but the feasibility of switching patients with intensified IFX therapy remains unknown. We assessed the clinical and pharmacological evolution after switching from IV to SC IFX in IBD patients to evaluate the feasibility and to determine the equivalence between IV and SC doses. Methods All IBD patients in clinical remission (CDAI &amp;lt;, 150 or partial Mayo score ≤, 2) were consecutively included in, 3 IBD centers and were switched to SC IFX, 120mg/2 weeks (wk) (regardless of IV dose) at the theoretical day of IV infusion (visit, 0 = V0) and were followed every, 4 to, 8 weeks according to the initial IV regimen for, 6 months. Results Among, 246 screened patients, 65 (26.4%) were not eligible (no clinical remission or physician’s decision), and, 71.8% (130/181) accepted to switch to SC IFX (Crohn’s disease = 73,1%, concomitant immunosuppressant = 25.4%, median faecal calprotectin = 35 µg/g [16–104])., 43.1% of the, 130 patients received, 5mg/kg/8 wk. In, 130 patients, clinical relapse leading to therapeutic escalation was observed in, 11.1% including, 4.0%, 8.6%, 11.1% and, 40.0% in patients treated with, 5mg/kg/8wk, 10 mg/kg/8wk, 10mg/kg/6 wk and, 10mg/kg/4 wk, respectively. Dose increase (240 mg/2 wk) induced clinical remission in, 92.3% of relapsers. Infliximab trough levels (TL) were significantly higher after switching from IV to SC IFX:, 9.8 ±6.4 vs, 14.4 ±5.7 (p&amp;lt;0.0001). TL increased in patients receiving, 5 mg/kg/8 wk (6.3 ±, 3.4 vs, 14.7 ±5.7; p&amp;lt;0.0001) or, 10 mg/kg/8 wk (8.4 ±5.6 vs, 13.7 ±6.6; p=0.001) but remained stable in those treated with, 10 mg/kg/6 wk (11.1 ±7.6 vs, 13.1 ±5.1; p=0.31) or, 10 mg/kg/4 wk (17.8 ±4.2 vs, 15.8 ±4.6; p=0.12) (Figure, 1). Infliximab TL remained stable (variation V1-V0 &amp;lt; ±, 1) in, 4.3%, 15.0 %, 33.3 % and, 50.0 % of the patients with the following IV doses:, 5 mg/kg/8 wk, 10 mg/kg/8 wk, 10 mg/kg/6 wk and, 10 mg/kg/4 wk, respectively (p=0.003). No patient developed anti-IFX antibodies. TL before the switch (8.4 ±5.6 for non-relapsers vs, 12.0 ±7.2 for relapsers; p=0.12) and TL after the switch (14.5 ±5.6 vs, 13.6 ±5.6; p=0.63) were not significantly associated with the risk of relapse. In contrast, the risk of relapse was higher in patients with stable or decreasing TL after the switch compared to those with increased TL (31.8% vs, 7.1%; p=0.024). The type of IBD and concomitant immunosuppressant were not associated with the risk of relapse. Patients’ acceptability was better with SC injections compared to IV infusions (10pts-acceptability numerical scale = 8.7 ±1.6 vs, 6.8 ±0.9; p&amp;lt;0.0001). Conclusion Switching from IV to SC IFX is feasible and well-accepted leading to a low risk of relapse in patients with IBD.

P319 Incorporating HLADQA1*05 in pre-biologic screening in IBD patients initiating biologic therapies

Abstract Background The PANTS study reported high risk of immunogenicity and loss of response in anti Tumor Necrosis Factor (anti-TNFs) treated Crohn’s disease (CD) patients carrying HLADQA1*05 allele. The proposed biomarker stratified trial to evaluate the usefulness of HLA testing prior to initiation of anti-TNFs is not yet available. We aimed to evaluate the use of HLADQA1*05 as part of pre-biologic screening in IBD patients initiating biologics on MDT decision on drug choice and disease outcomes Methods We prospectively included all IBD patients who had HLADQA1*05 tested prior to initiation of biologics over a period of, 12 months. Patients with definitive indication for one class of drug or drug strategy (perianal fistula, acute severe colitis, contraindications to infliximab, co-existent EIMs) were excluded. Primary outcome was treatment persistence at, 6 and, 12 months. Secondary outcomes were steroid free remission at, 6 and, 12 months, use concomitant immunosuppression and proportion needing dose escalation. Results Seventy-six patients were included in analysis (UC=, 32, CD=43, IBD-U =1). HLADQA1*05 was positive in, 46.7% of patients. The therapy class choice was as recorded in figure 1. Concomitant immunosuppression was used in, 44% of the whole cohort and in, 100% of HLADQA1*05 positive patients started on anti-TNF agents. Primary non-response was recorded in, 8 patients and secondary loss of response in, 3 patients. Among patients started on anti-TNFs, anti-drug antibodies were detected in, 10 (15.6%) patients with, 7 out of, 10 positive for HLADQA1*05. However, only, 3 (4.6%) had undetectable drug levels in the presence of antibody and all three were HLADQA1*05 positive. Two patients had reactions during induction therapy both were HLADQA1*05 positive and were on combination therapy with Infliximab. Therapy persistence with initial drug strategy and steroid free remission at, 6 months was recorded in, 77.1% and, 78% respectively. There was no significant difference in drug persistence rates at, 6 months and, 12 months in patients with HLADQA1*05 variant or those with variant absent (Figure, 2). Steroid free remission at, 6 and, 12 months was also similar irrespective of the variant status (Figure 3) Conclusion Choice of therapy incorporating HLADQA1*05 status may allow anti-TNF monotherapy and tailoring of therapy in IBD patients. A randomised stratified biomarker trial is required to determine the utility of pre-treatment testing.

P292 Association of golimumab trough concentrations during maintenance with endoscopic and histologic remission in patients with ulcerative colitis

Abstract Background The aim of this study was to investigate the association of serum golimumab concentrations (SGC) during maintenance therapy in UC with clinical outcomes including endoscopic and histologic healing. Methods This multicentre, cross-sectional cohort study included UC patients who had received at least 5 maintenance doses of golimumab. A colonoscopy was scheduled, and study-specific recto-colonic biopsies were taken for blind central histologic reading. Samples for trough SGC and anti-golimumab antibodies (AGA) were collected on the day of the scheduled golimumab administration closest to the colonoscopy. Definitions: clinical remission = partial Mayo score (PMS) ≤2 with no individual subscore &amp;gt;1, combined clinical-biochemical remission = PMS ≤2 + faecal calprotectin &amp;lt;300 μg/g, endoscopic healing = Mayo endoscopic subscore of 0, deep remission = clinical remission + endoscopic healing, histologic remission = Geboes index ≤2.0, and disease clearance = clinical remission + endoscopic healing + histologic remission. Results Fifty-two patients were included. The overall median SGC was 1.79 µg/ml (interquartile range [IQR] 0.87–2.79). Three patients (5.7%) had undetectable SGC together with positive AGA. With a median of 23 [IQR 15–32] months of golimumab therapy, 46 patients (88%) were in clinical remission, 26 (52%) had combined clinical-biochemical remission, 18 patients (35%) had both endoscopic healing and deep remission, 21 (40%) had histologic remission, and 14 (27%) had disease clearance. Median SGC were significantly higher in patients who were in clinical remission (2.01 versus 0.72 µg/mL, P=0.047) µg/mL, combined clinical-biochemical remission (2.21 versus 1.47 µg/mL, P=0.041), mucosal healing and deep remission (2.52 versus 1.47 µg/mL, P=0.003), histologic remission (2.33 versus 1.50 µg/mL, P=0.02), and disease clearance (2.52 versus 1.70 µg/mL, P=0.009), compared with those not meeting these criteria. (Figure 1) The higher SGC quartiles were associated with higher rates of mucosal healing (P=0.005), and histologic remission (P=0.006). (Figure 2) Receiver-operating characteristic analyses identified SGC thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.65], 2.29 [0.75], and 2.29 [0.72] µg/mL be associated with clinical remission, combined remission, deep remission, and disease clearance, respectively. (Table 1) On multivariate analysis, body mass index (P=0.021) and CRP level (P=0.040) were linearly associated with lower SGC, and concomitant immunosuppressant with higher SGC (P=0.47). (Table 2) Conclusion We identified SGC thresholds during maintenance most closely associated with clinical outcomes including endoscopic and histologic healing. Higher SGC are needed to achieve increasingly stringent therapeutic targets.

P531 Stringent screening strategy significantly reduces reactivation rate of Tuberculosis in Patients with Inflammatory Bowel Disease on anti-TNF therapy in a TB endemic region

Abstract Background Anti-tumour necrosis factor (anti-TNF) therapy use in patients with inflammatory bowel disease (IBD) leads to increased risk of tuberculosis (TB) reactivation despite LTB screening, especially in TB endemic regions. We evaluated the effect of stringent screening strategy and latent tuberculosis (LTB) prophylaxis on TB reactivation. Methods We performed an ambispective comparison between patients who were started on anti-TNF therapy after January 2019 (Cohort A) and between Jan 2005-Dec 2018 (Cohort B). Cohort A patients were subjected to stringent screening criteria which included all: history of past TB/recent contact with active TB, CT (computed tomography) chest, IGRA (interferon-gamma release assay), TST (tuberculin skin test), and if any positive were given chemoprophylaxis. A cohort comparison was done to evaluate for risk reduction of TB following the stringent screening strategy. Results One hundred seventy-one patients (63-Ulcerative colitis/108-Crohn’s disease; mean age diagnosis-28.5±13.4 years; 60% males; median follow-up duration after anti-TNF:33months [interquartile range, 23–57 months]) were included. Among 112 in Cohort B 22(19.6%) had LTB and 19(17%) developed TB. In comparison, 26(44%) had LTB and only 1(1.7%) developed TB in Cohort A (p&amp;lt;0.01). On survival analysis, patients in Cohort B had a higher probability of TB reactivation compared to Cohort A at 5 years of follow up, HR-14.39 (95% CI,1.88- 109.81[p=0.010]) after adjusting for gender, age at anti-TNF therapy initiation, concomitant immunosuppression, the total number of anti-TNF doses and therapy escalation. *Log rank p value=0.006 Figure 1: Kaplan Meier curve analysis for probability of remaining free from tuberculosis between patients who were started on anti- TNF therapy till January 2019 (Cohort B) and those who were started on anti-TNF after January 2019 (Cohort A). *Log rank p value=0.02 Figure 2: Kaplan Meier curve analysis for probability of remaining free from tuberculosis between patients who had incomplete latent TB screening and those with complete TB screening. Conclusion The high risk of TB reactivation with anti-TNF therapy in TB endemic regions can be significantly mitigated with stringent LTB screening and chemoprophylaxis.

Latent class analysis of 216 patients with adult-onset Still\u2019s disease

BackgroundAdult-onset Still’s disease (AOSD) is a rare systemic autoinflammatory disease which encompasses patients with heterogenous presentation and a wide range of clinical courses. In this study, we aimed to identify potential subgroups of AOSD and reveal risk factors for relapse.MethodsWe included a total of 216 AOSD patients who received treatment in nine hospitals between 2000 and 2019. All patients fulfilled the Yamaguchi classification criteria. We retrospectively collected information about baseline characteristics, laboratory tests, treatment, relapse, and death. We performed latent class analysis and time-to-event analysis for relapse using the Cox proportional hazard model.ResultsThe median age at disease onset was 51.6 years. The median follow-up period was 36.8 months. At disease onset, 22.3% of the patients had macrophage activation syndrome. The median white blood cell count was 12,600/μL, and the median serum ferritin level was 7230 ng/mL. Systemic corticosteroids were administered in all but three patients (98.6%) and the median initial dosage of prednisolone was 40mg/day. Ninety-six patients (44.4%) were treated with concomitant immunosuppressants, and 22 (10.2%) were treated with biologics. Latent class analysis revealed that AOSD patients were divided into two subgroups: the typical group (Class 1: 71.8%) and the elderly-onset group (Class 2: 28.2%). During the follow-up period, 13 of 216 patients (6.0%) died (12 infections and one senility), and 76 of 216 patients (35.1%) experienced relapses. Overall and relapse-free survival rates at 5 years were 94.9% and 57.3%, respectively, and those rates were not significantly different between Class 1 and 2 (p=0.30 and p=0.19). Time-to-event analysis suggested higher neutrophil count, lower hemoglobin, and age ≥65 years at disease onset as risk factors for death and age ≥65 years at disease onset as a risk factor for relapse.ConclusionsAOSD patients were divided into two subgroups: the typical group and the elderly-onset group. Although the survival of patients with AOSD was generally good, the patients often experienced relapses. Age ≥65 years at disease onset was the risk factor for relapse.

Retrospective Database Analysis: Dose Escalation and Adherence in Patients Initiating Biologics for Ulcerative Colitis

Background: Biologic therapies are often used in patients with ulcerative colitis (UC) who are nonresponsive to conventional treatments. However, nonresponse or loss of response to biologics often occurs, leading to dose escalation, combination therapy, and/or treatment switching. We investigated real-world treatment patterns of biologic therapies among patients with UC in the USA. Methods: This study analyzed data from the IBM^® MarketScan^® Commercial and Medicare Supplemental Databases (medical/pharmacy claims for >250 million patients in the USA) to identify patients with UC initiating a biologic therapy (adalimumab, infliximab, golimumab, or vedolizumab) with 12 months of follow-up post-initiation. Key measures were patient baseline characteristics, dose escalation (average maintenance dose >20% higher than label), adherence (proportion of days covered), and ulcerative colitis-related healthcare costs in the 12 months following biologic therapy initiation. Results: Of 2,331 patients included in the study (adalimumab [N = 1,291], infliximab [N = 810], golimumab [N = 127], and vedolizumab [N = 103]), 28.1% used concomitant immunosuppressant therapy within 12 months post-initiation. Overall, 23.6% (adalimumab), 34.8% (infliximab), 9.9% (golimumab), and 39.2% (vedolizumab) of patients dose escalated within 12 months. Patients who dose escalated incurred USD 20,106 higher total UC-related healthcare costs over 12 months than those who did not. Adherence (covariate-adjusted proportion of days covered) ranged from 0.63 to 0.73, and 39.3% of patients discontinued within 12 months (median treatment duration = 112 days). Conclusion: Dose escalation was common, and incurred higher costs, in patients with UC initiating biologic therapies. Suboptimal adherence and/or discontinuation within 12 months of initiation occurred frequently, highlighting the challenges in managing these patients.

Disease burden and treatment sequence of polymyositis and dermatomyositis patients in Japan: a real-world evidence study

Introduction/objectivesSince new consensus on polymyositis (PM) and dermatomyositis (DM) were released in Japan, an updated evidence on treatment landscape and PM/DM burden was essential. This study evaluates treatment burden and overall treatment cost of PM/DM-related inpatient and outpatient visits, treatments, and procedures/patient/year.MethodThis retrospective, observational study analyzed insurance claims from Japan Medical Data Center (JMDC) database. Patients with at least one PM/DM diagnosis/one dispensation of treatment between 1 January 2009 and 31 December 2019 were enrolled. Patient characteristics, treatment patterns and sequence, treatment choices, healthcare resource utilization (HCRU), and related costs were assessed. Chi-square test and linear regression model were used to assess impact of patient characteristics on treatment choice.ResultsPatients (836/4,961) receiving a relevant treatment were analyzed. Heart disease (35%), interstitial lung disease (27%), and diabetes mellitus (26%) were frequently identified as comorbidities. Concomitant dispensation of immunosuppressants and systemic steroids was largely found in first and second line of treatment (LoT) while systemic steroids remained as single dominant treatment across all LoTs. HCRU was very low for inpatient visits (0.68 [1.43]) or rehabilitation (4.74 [14.57]). The mean (SD) number of inpatient visits decreased from first (1.23 [2.32]) to third year (0.11 [0.54]). Total mean (SD) healthcare cost per patients per year was ¥ 3,815,912 (7,412,241), with overall drug dispensation compounding to 80% of total cost.ConclusionsHigh concomitant immunosuppressant and systemic steroid prescriptions in first LoT recommend early optimal treatment to manage PM/DM. Although inpatient costs are low, outpatient dispensation costs increase overall economic burden.Key Points• Japan faces treatment challenges in the prognosis of polymyositis (PM) and dermatomyositis (DM) and thus, we assessed the real-world treatment landscape, practice, patterns, and healthcare resource utilization as an evidence to support healthcare outcome improvement and treatment burden reduction.• Systemic steroids were the dominant preferred choice of treatment, but it increases the overall cost of the treatment due to the resultant comorbidities considering possible side-effects promotion.• Thus, an increased awareness towards the disease management among patients and medical doctors is required for better management goals based on this real-world practice evidence.

Clinical characteristics of patients with polyarteritis nodosa based on a nationwide database in Japan.

This study aimed to clarify the epidemiological and clinical features and treatment of patients with polyarteritis nodosa (PAN) in Japan. We used the database of the Ministry of Health, Labour and Welfare (MHLW) of Japan in 2013 and 2014. We analysed 121 patients who were antineutrophil cytoplasmic antibodies negative among the patients certified as PAN according to the MHLW diagnostic criteria. The analysis included 60 males and 61 females, with a mean age of 52.9 ± 21.0 years. As a general manifestation, fever was observed in 53.7%. Regarding organ involvement, skin manifestations (82.6%), joint and muscle manifestations (75.2%), and neuropsychiatric manifestations (50.4%) were common. Male patients had a higher proportion of mononeuritis multiplex involving motor neuropathy than female patients. Elderly patients had a higher proportion of general and respiratory manifestations. Glucocorticoids were used for treatment in all patients, and 19.0% underwent methylprednisolone pulse. Concomitant immunosuppressants were used in 25.6%, one-third of whom received cyclophosphamide. Methylprednisolone pulse and cyclophosphamide were mostly used in patients with life-threatening organ involvement. PAN developed in middle-aged people and led to numerous clinical manifestations. The common manifestations varied with age, and treatment was determined based on the type of organ involvement and disease severity.

CAR-T therapy in solid transplant recipients with post-transplant lymphoproliferative disease: case report and literature review

Patients with postransplant lymphoproliferative disease (PTLD) who are refractory to rituximab-based regimens have extremely poor prognosis. Data is lacking in the setting of solid organ transplantation (SOT)-related PTLD treated with chimeric antigen receptor T-cell (CAR-T) therapy. Moreover, limited information is available on the influence of concomitant immunosuppressive drugs on CAR-T function. Here, we describe the clinical outcome in one PTLD patient and propose a strategy for tailoring immunosuppressive treatment and organ monitoring in patients with kidney allografts after CAR-T infusion. This report also reviews the limited published data in the setting of SOT-related PTLD treated with CAR-T, which appears to be a feasible treatment in this clinical scenario, without severe toxicity and capable of inducing sustained responses. A noteworthy finding is that in most reported cases patients underwent complete or partial discontinuation of immunosuppressive drugs, with only one documented case of allograft rejection.

Differentiation of Pulmonary Lymphoma Manifestations and Nonlymphoma Infiltrates in Possible Invasive Fungal Disease Using Fast T1-weighted Magnetic Resonance Imaging at 3 T Comparison of Texture Analysis, Mapping, and Signal Intensity Quotients.

This study aimed to evaluate the diagnostic performance of texture analysis (TA), T1 mapping, and signal intensity quotients derived from fast T1-weighted gradient echo (T1w GRE) sequences for differentiating pulmonary lymphoma manifestations and nonlymphoma infiltrates in possible invasive fungal disease in immunocompromised hematological patients. Twenty patients with hematologic malignancies and concomitant immunosuppression (including 10 patients with pulmonary lymphoma manifestations and 10 patients with nonlymphoma infiltrates) prospectively underwent 3 T magnetic resonance imaging using a conventional T1w GRE sequence and a T1w GRE mapping sequence with variable flip angle. A region of interest was placed around the most representative lesion in each patient. TA was performed using PyRadiomics. T1 relaxation times were extracted from precompiled maps and calculated manually. Signal intensity quotients (lesion/muscle) were calculated from conventional T1w GRE sequences. Of all TA features, variance, mean absolute deviation, robust mean absolute deviation, interquartile range, and minimum were significantly different between the 2 entities (P<0.05), with excellent diagnostic performance in receiver operating characteristic analysis (area under the curve [AUC] >80%). Neither T1 relaxation times from precompiled maps (AUC=63%; P=0.353) nor manual calculation (AUC=63%; P=0.353) nor signal intensity quotients (AUC=70%; P=0.143) yielded significant differences. TA from fast T1w GRE images can differentiate pulmonary lymphoma manifestations and nonlymphoma infiltrates in possible invasive fungal disease with excellent diagnostic performance using the TA features variance, mean absolute deviation, robust mean absolute deviation, interquartile range, and minimum. Combining a fast T1w GRE sequence with TA seems to be a promising tool to differentiate these 2 entities noninvasively.

Subcutaneously Administered Anti-TNFs for the Treatment of Ulcerative Colitis: A Retrospective, Propensity Score-Matched, US Health Claims Analysis.

Adalimumab and golimumab are subcutaneously administered anti-tumor necrosis factor α (TNFα) biologics used in the treatment of ulcerative colitis (UC). To date, no studies have directly compared treatment patterns and healthcare resource utilization (HRU) among patients with UC receiving these therapies in a real-world setting. The objective of this study was to compare these outcomes among patients with UC treated with either adalimumab or golimumab using a US claims database. Patients with UC treated with golimumab or adalimumab were identified using the US Optum Clinformatics® Data Mart database. Outcomes of interest included treatment patterns (discontinuations, dose optimizations, persistence, and concomitant medication use) and HRU (outpatient office visits, emergency room [ER] visits, and inpatient stays). Propensity score matching (PSM) was used to account for differences in confounding variables between groups. Overall, 990 patients were identified (golimumab: n = 277; adalimumab: n = 713). After PSM, 246 patients were included in each group. There were no significant differences between the adalimumab and golimumab groups over the full follow-up period in terms of treatment discontinuations (53.7% vs. 51.2%; P = 0.5881), dose optimizations (35.4% vs. 39.4%; P = 0.3515), or persistence (338.2 vs. 361.2days; P = 0.4194). During the year after initiating therapy, there were no significant differences in concomitant immunosuppressant (21.9% vs. 21.7%; P = 0.9686) or corticosteroid use (74.7% vs. 78.8%; P = 0.3573) or in HRU outcomes including outpatient office visits (93.3% vs. 94.0%; P = 0.7660), ER visits (15.2% vs. 10.9%; P = 0.2238), and inpatient stays (15.2% vs. 13.6%; P = 0.6680). In this nationwide PSM cohort study of patients with UC receiving golimumab or adalimumab, no significant differences were observed between groups for treatment patterns or HRU outcomes. High rates of concomitant corticosteroid use, treatment discontinuations, and HRU while on therapy highlight key unmet needs in the treatment of UC.

A comparative study of human-and rhesus-specific antithymocyte globulins in Rhesus macaques.

Rabbit antithymocyte globulin (RATG) preparations are widely used in transplantation. They are developed in vivo against thymocytes and contain polyclonal antibodies specific for myriad cellular targets. The rhesus monkey is commonly used as a preclinical transplant model, but the fidelity of commercially available human-specific RATGs to anticipate the effects of RATGs in rhesus has not been established. We therefore developed two rhesus-specific ATGs (rhATG) and compared them to human-specific RATG (huATG, Thymoglobulin® ) in rhesus monkeys, assessing the magnitude and phenotype of depletion peripherally and in lymph nodes. Four primates were assigned to each group and received 20mg/kg of drug. Depletion, repopulation, and changes in lymphocyte subsets were evaluated in peripheral blood and lymph nodes by flow cytometry over four months. We observed similar qualitative changes in lymphocyte subsets, but a generally more profound depletion with huATG compared to either rhATG. Peripheral homeostatic proliferation rather than thymic output was the major mechanism for repopulation with all RATGs. Repopulation was slower but qualitatively similar when examining RATGs in additional animals receiving concomitant chronic immunosuppression. Depletional induction is similar to human- and rhesus-specific RATGs in rhesus macaques. Both rhesus- and human-specific agents appear appropriate for preclinical modeling of clinical RATG use.

P509 Influence of concomitant immunosuppresives in retention rate in Crohn′s Disease patients under ustekinumab in the SUSTAIN Study

Abstract Background Whether to use biologic treatment for inflammatory bowel disease as monotherapy or in combination with immunosuppressives has been a matter of debate in the last years. We aimed to evaluate if immunosuppressants influenced the retention rate of ustekinumab in Sustain, the largest study evaluating its use in clinical practice, having the longest follow-up period reported to date. Methods Retrospective, multicentre study (&amp;gt;60 sites) including patients with active Crohn′s Disease (CD) [(Harvey-Bradshaw (HBI)&amp;gt;4)] who received ≥1 dose of ustekinumab intravenously before July 2018. Data on concomitant immunomodulatory therapy (if any) with azathioprine, mercaptopurine, methotrexate or others at the start of ustekinumab treatment and during follow-up were documented. Clinical remission was defined as HBI≤4 and response as ≥3 points decrease from baseline. Loss of response (LoR) was defined as reappearance of symptoms that led to intensifying the treatment dose, adding another medication to control CD, switching or surgery in patients with short-term remission. The retention rate in patients on ustekinumab receiving or not immunosuppressive treatment was evaluated by descriptive analysis and Kaplan-Meier survival curves. Predictive factors were assessed by Cox-regression. Data quality was assured by remote monitoring. Results 463 CD patients were included. Prior CD treatments to ustekinumab were collected: the majority of patients received steroids, immunosuppressants and biologics. Figure 1 shows the percentage of patients on treatment with each type of drug and whether or not they continued to receive it when they started ustekinumab, in the case of steroids and immunosuppressants. Reasons for discontinuation of previous immunosuppressive treatments for CD were as follows: failure (37.5%), sustained remission (5.8%), adverse event (47.6%), medical decision (4%), other reasons (5.1%). During ustekinumab treatment, 163 patients (35.2%) received immunosuppressants (listed in figure 2). Sixty-six (14.3%) patients had their immunosuppressant withdrawn during treatment. Retention was observed in 77.9% of patients with concomitant immunosuppressive therapy versus 76.3% of patients without. There weren′t statistically significant differences between the two populations (p=0.712). Figure 3. The patient-year discontinuation rate for patients who didn′t receive concomitant immunosuppressants was 17.5 versus 18.9 in those who received them. Conclusion No effectiveness differences were seen by adding immunosuppressants to ustekinumab, reinforcing the low immunogenic profile of this drug and reducing the risk of additional side effects and toxicity.

P402 Is co-trimoxazole prophylaxis necessary for Inflammatory Bowel Disease patients receiving triple immunosuppression?

Abstract Background ECCO Guidelines (1) advocate Co-trimoxazole (TMP/SMX) prophylaxis against Pneumocystis jirovecii for patients with inflammatory bowel disease (IBD) on triple immunosuppression, although the evidence level is low and based on non-IBD patient data (2). We assessed adherence to this guidance and frequency of infection events among IBD patients at Imperial College Healthcare NHS Trust, London, UK. Methods Eligible patients were defined as those on a combination of 2 immunosuppressants (with one of those being a biologic) between December 2017 to December 2020, who received a course of high dose steroids (≥20mg prednisolone). Patient demographics, IBD treatment, TMP/SMX prophylaxis and infections (including hospitalisation) developed within 30-days of starting high dose steroids were recorded retrospectively using the hospital electronic patient records. Results In the cohort of 247 patients on concomitant biologic and immunosuppression dual therapy 176/247 (71%) were ≤ 49 years old and 136/247 (55%) were male. Over the three year observation period, 333 individual thiopurine-biologic combinations were prescribed; Of the biologics 157/333 (47%) were infliximab, 91/333 (27%) adalimumab, 50/333 (15%) vedolizumab, 27/333 (8%) ustekinumab and 8/333 tofacitinib (3%). All received azathioprine or 6MP concurrently. Steroids were prescribed on 75 occasions for 50 (20%) patients. Of 28/75 (37%) prescriptions where TMP/SMX was co-prescribed 4/28 (14%) developed infections with 1/28 (4%) requiring hospitalisation. There were no respiratory infections in this group. Of the 47/75 (63%) where TMP/SMX was not prescribed 7/47 (15%) developed infections (4/47 respiratory, 2/47 skin or bone, 2/47 [MZ1] gastrointestinal infections). One patient had 2 infections. The hospitalisation rate was 2/47 (4%). There were no confirmed cases of Pneumocystis jirovecii in either group. Conclusion Existing evidence for TMP/SMX prophylaxis in this setting is limited and is reflected in the varied clinical practice observed. However, no difference in clinically significant infection rates among individuals with and without TMP/SMX prophylaxis was observed in our setting. Further data are required to validate the utility of antibiotic prophylaxis in severely immunosuppressed IBD cohorts to better guide its use. References

P600 Real-world clinical characteristics and therapeutic strategies in patients with moderate-to-severe Inflammatory Bowel Disease in Argentina: Data from the RISE AR study

Abstract Background Evidence on the adoption of different pharmacologic strategies in inflammatory bowel disease (IBD) in the real-world setting in Latin America is scarce. Herein, we describe the clinical characteristics and therapeutic strategies of IBD patients (pts) in Argentina. Methods RISE AR (NCT03488030) was a multicentre, non-interventional study with a cross-sectional evaluation and a 3-year retrospective data collection period conducted in Argentina (12/2018-05/2019) to assess the use of IBD treatments. Adult pts (≥18 years old) with a previous diagnosis of moderate-to-severe ulcerative colitis (UC) or Crohn′s disease (CD) based on clinical, endoscopic or imaging criteria at least 6 months prior to enrolment, were included. Results Overall, 101 CD and 145 UC pts were included. Median (range) age (years) at enrolment was 39.5 (18.2–74.0) for CD (51.2% female) and 41.9 (18.0–80.4) for UC (55.2% female); median (range) disease duration (years) was 7.4 (0.6–36.9) for CD and 5 (0.7–33.8) for UC. At enrolment, 51.5% of CD pts had colonic involvement, 32.7% ileocolonic, 8.9% ileal, 1% isolated upper tract and 5.9% had combined L4/other. In UC, 46.2% had extensive colitis, 44.7% left-sided colitis and proctitis 9.1%. 51.6% of CD pts had non-inflammatory behaviour (37.7% stricturing; 13.9% penetrating), and 34% had perianal disease (13.9% as B1p), resulting in a total of 65.5% pts with complicated disease. Only 9.3% of CD (Harvey Bradshaw Index ≥8) and 7.7% of UC (partial Mayo Score ≥5) pts showed moderate-to-severe disease activity at enrolment. In CD, 70.3% of pts were receiving a biologic agent vs. 29.7% of UC pts. Immunosuppressant (IMM) use was similar between groups (CD 39.6%, UC 40.0%); nearly one-third of the pts on a biologic were receiving concomitant IMM (CD 33.8%, UC 34.9%). Aminosalicylates (5-ASA) were used for most UC pts (89.0%) vs. 47.5% of CD pts, mainly in those with L2 disease. 5-ASA monotherapy was prescribed in 32.1% of UC vs. 5.3% of CD pts, but were also used with IMM (UC 25%, CD 11%), biologics (UC 15%, CD 11.6%) or all three therapies combined (UC 6.4%, CD 17.9%). Corticosteroids (CS) were the least prescribed therapy (CD 7.9%, UC 13.8%). IBD treatments ever prescribed during the retrospective period were (CD, UC): biologics: 79.2%, 33.8%; IMM: 65.3%, 58.6%; 5-ASA: 62.4%, 97.9%; CS: 55.4%, 69.7%. Conclusion In this cohort of IBD patients, biologics use was high, especially among CD patients, in line with disease behaviour, and possibly by their increased availability in these reference centres. This study also highlights country-specific clinical features such as the low proportion of CD pts and the high prevalence of colonic involvement in CD.