Maintenance Of Remission Research Articles

Long-term efficacy and survival of ustekinumab therapy in patients with inflammatory bowel disease

The article reviews data on the long-term effectiveness and survival of biological therapies for treating inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease. It highlights the shift in treatment goals, emphasizing not only induction and maintenance of remission but also long-term outcomes. The choice of therapy is becoming increasingly complex, as it must consider both clinical efficacy and endoscopic remission, which, serves as a predictor of long-term treatment effectiveness. Special attention is given to ustekinumab – antibodies targeting interleukins 12 and 23. This drug has shown high long-term effectiveness and safety in treating ulcerative colitis and Crohn’s disease. Studies indicate that ustekinumab effectively maintains clinical remission in patients, providing stable results and a low rate of serious adverse events. Long-term data also highlight its advantages over other biological agents, such as infliximab and adalimumab, in terms of therapy sustainability. The article includes data from clinical trials of ustekinumab extending up to 5 years, demonstrating good treatment sustainability, as well as various real-world practice studies confirming the prolonged effectiveness of ustekinumab in patients with ulcerative colitis and Crohn’s disease. The article evaluates and analyzes these data on long-term effectiveness and drug survival and also emphasizes the importance of an individualized approach in selecting therapy, taking into account prior treatment experience and inflammation activity.

Low Anti-Tumor Necrosis Factor Levels During Maintenance Phase Are Associated With Treatment Failure in Children With Crohn's Disease.

Higher drug levels and combination therapy with low-dose oral methotrexate (LD-MTX) may reduce anti-tumor necrosis factor (TNF) treatment failure in pediatric Crohn's disease. We sought to (1) evaluate whether combination therapy with LD-MTX was associated with higher anti-TNF levels, (2) evaluate associations between anti-TNF levels and subsequent treatment failure, and (3) explore the effect of combination therapy on maintenance of remission among patients with therapeutic drug levels (>5 µg/mL for infliximab and >7.5 µg/mL for adalimumab). We conducted a post hoc analysis of the COMBINE trial, which compared anti-TNF monotherapy to combination therapy with LD-MTX. We included participants who entered maintenance therapy and provided a serum sample approximately 4 months from randomization. Among 112 infliximab and 41 adalimumab initiators, median drug levels were similar between combination therapy and monotherapy (infliximab: 8.8 vs 7.5 μg/mL [P = .49]; adalimumab: 11.1 vs 10.5 μg/mL [P = .11]). Median drug levels were lower in patients experiencing treatment failure (infliximab: 4.2 vs 9.6 μg/mL [P < .01]; adalimumab: 9.1 vs 12.3 μg/mL [P < .01]). Among patients treated with infliximab with therapeutic drug levels, we observed no difference in treatment failure between participants assigned monotherapy or combination therapy. Among patients treated with adalimumab, a trend towards reduced treatment failure in the combination therapy arm was not statistically significant (P = .14). LD-MTX combination was not associated with higher drug levels, but higher drug levels were associated with reduced risk of treatment failure. Among patients with therapeutic drug levels, we observed no benefit of LD-MTX for patients treated with infliximab. A nonsignificant trend towards reduced treatment failure with the addition of LD-MTX patients treated with adalimumab warrants further investigation.

S1923 Comparison of Efficacy and Safety of Mycophenolate Mofetil With Standard Therapy in Autoimmune Hepatitis for Induction and Maintenance of Remission: A Systematic Review and Meta-analysis

S1923 Comparison of Efficacy and Safety of Mycophenolate Mofetil With Standard Therapy in Autoimmune Hepatitis for Induction and Maintenance of Remission: A Systematic Review and Meta-analysis

S1060 Efficacy and Safety Profile of Small Molecules for Induction and Maintenance of Remission in Ulcerative Colitis: A Systematic Review of Randomised Control Trials

S1060 Efficacy and Safety Profile of Small Molecules for Induction and Maintenance of Remission in Ulcerative Colitis: A Systematic Review of Randomised Control Trials

A Pilot Study on the Efficacy and Safety of Rituximab in the Maintenance of Remission in Adults with Minimal Change Disease

A Pilot Study on the Efficacy and Safety of Rituximab in the Maintenance of Remission in Adults with Minimal Change Disease

Comparative Efficacy of Advanced Therapies for Management of Moderate-to-Severe Ulcerative Colitis: 2024 American Gastroenterological Association Evidence Synthesis

We performed an updated systematic review and network meta-analysis to inform the 2024 American Gastroenterological Association (AGA) Clinical Guidelines on the management of moderate-to-severe ulcerative colitis (UC). We searched multiple electronic databases through November 21, 2023, to identify randomized controlled trials in adults with moderate-to-severe UC, comparing different advanced therapies (tumor necrosis factor antagonists, vedolizumab, sphingosine-1-phosphate receptor modulators, interleukin 12/23 or selective interleukin 23 antagonists, and Janus kinase [JAK] inhibitors) against placebo or another active comparator. Our primary outcomes were induction and maintenance of clinical remission, and our secondary outcome was endoscopic improvement. We performed a network meta-analysis using a frequentist approach and applied Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to appraise certainty of evidence. After excluding JAK inhibitors as potential first-line treatment (in accordance with the United States Food and Drug Administration), low-certainty evidence supports clinically important benefit with infliximab, ozanimod, risankizumab, and guselkumab over adalimumab and mirikizumab for achieving remission with induction therapy in biologically naïve patients with moderate-to-severe UC, with risankizumab and ozanimod being ranked the highest for induction of clinical remission. With the inclusion of JAK inhibitors as first-line therapy, upadacitinib was more efficacious compared with all other medications except ozanimod and risankizumab, with low- to moderate-certainty evidence. In patients with prior biologic exposure, upadacitinib, tofacitinib, and ustekinumab were ranked highest for achieving remission. Using Grading of Recommendations, Assessment, Development and Evaluation to appraise quality of evidence, this updated network meta-analysis will be used to inform comparative efficacy and positioning of advanced therapies for the treatment of biologic-naïve and biologic-exposed patients with moderate-to-severe UC.

Harms with placebo in trials of biological therapies and small molecules as maintenance therapy in inflammatory bowel disease: a systematic review and meta-analysis

Randomised placebo-controlled trials for the induction of inflammatory bowel disease (IBD) remission involve potential harms to those receiving placebo. Whether these harms are also apparent with placebo during maintenance of remission trials in IBD is unclear. We aimed to examine the potential harms associated with receiving placebo in trials of licensed biologics and small molecules for maintenance of remission of ulcerative colitis and luminal Crohn's disease in a meta-analysis. We performed a systematic review and meta-analysis. We searched several medical literature databases including MEDLINE (from Jan 1, 1946, to May 31, 2024), Embase and Embase Classic (Jan 1, 1947, to May 31, 2024), and the Cochrane Central Register of Controlled Trials from database inception to May 31, 2024, for randomised placebo-controlled trials of licensed biologics and small molecules for maintenance of remission in adults with IBD reporting data on adverse events over a period of 20 weeks or more. There were no language restrictions or prespecified exclusion criteria. We extracted summary data and pooled data using a random-effects model for any treatment-emergent adverse event, drug-related adverse event, infection, worsening of IBD activity, withdrawal due to adverse events, serious adverse events, serious infection, serious worsening of IBD activity, or venous thromboembolic events, reporting relative risks (RRs) for placebo versus active drug with 95% CIs for each outcomes. The protocol for this meta-analysis was registered with PROSPERO (CRD42024542624). Our search identified 10 826 citations, of which 45 trials including 16 562 patients (10 319 [62·3%] receiving active drug and 6243 [37·7%] placebo) were eligible. The risks of any treatment-emergent adverse event (7297/9546 [76·4%] patients on active drug vs 4415/5850 [75·5%] on placebo; RR 1·01, 95% CI 0·99-1·04; I2 =47%), serious infection (260/10 242 [2·5%] vs 155/6149 [2·5%]; 0·97, 0·79-1·19; I2 =0%), or venous thromboembolic event (12/4729 [0·3%] vs 9/2691 [0·3%]; 0·72, 0·31-1·66; I2 =0%) were not significantly lower with active drug than placebo. The risks of any infection (3208/8038 [39·9%] vs 1713/4809 [35·6%]; 1·14, 1·05-1·23; I2 =60%) or any drug-related adverse event (1094/2997 [36·5%] vs 609/1950 [31·2%]; 1·24, 1·02-1·50; I2 =75%) were higher with active drug than placebo. However, the risks of any worsening of IBD activity (1038/8090 [12·8%] vs 1181/5191 [22·8%]; 0·58, 0·52-0·64; I2 =40%), any withdrawal due to adverse events (610/10 282 [5·9%] vs 561/6207 [9·0%]; 0·71, 0·60-0·84; I2 =43%), any serious adverse events (1066/10 292 [10·4%] vs 742/6198 [12·0%]; 0·85, 0·77-0·94; I2 =17%), or any serious worsening of IBD activity (101/5707 [1·8%] vs 143/3640 [3·9%]; 0·55, 0·42-0·71; I2 =0%) were lower with active drug than placebo. 21 randomised controlled trials were judged as low risk of bias across all domains. In maintenance of remission trials in IBD, placebo was associated with some clinically significant potential harms. Patients should be counselled about these before participating in clinical trials and consideration given to alternative designs to test novel drugs in IBD. None.

The Role of Topical Tacrolimus in the Management of Inflammatory Bowel Disease: A Comprehensive Review.

Management of ulcerative colitis and Crohn's disease, the main subtypes of inflammatory bowel disease (IBD), focuses on the induction and maintenance of remission. Tacrolimus, a member of a group of drugs termed calcineurin inhibitors, may have a role in the medical management of IBD when given either systemically or topically. This review aimed to evaluate the available data focusing on the use of topical tacrolimus in the management of IBD. Reports of the use of topical tacrolimus in IBD were extracted from databases up to 31 May 2024. Topical tacrolimus therapy appears to have reasonable efficacy in the induction and maintenance of remission in patients with refractory IBD, with an acceptable safety profile. Overall, the available data are supportive of the use of topical tacrolimus in selected patients. Further comparative clinical studies are required to more fully delineate the role of this drug.

Comparative Efficacy of Biologics and Small Molecule in Ulcerative Colitis: A Systematic Review and Network Meta-analysis

Background & aimsTreatment options for moderate to severe ulcerative colitis (UC) are increasing rapidly, but the lack of comparative efficacy trials makes treatment choices a clinical challenge. This network-meta-analysis aimed to compare the relative efficacy of biologics and small molecules in achieving remission in patients with moderate to severe UC. MethodsThe literature was searched up to May 2024. Phase 3 placebo or active comparator randomized controlled trials (RCTs) were included. The primary outcome was induction and maintenance of endoscopic improvement (Mayo endoscopic score [MES] ≤1). Secondary outcomes were the induction and maintenance of clinical remission, endoscopic (MES = 0) and histological remission. A sub-analysis was performed based on the RCT design and previous exposure to biologic therapy. ResultsWe identified 36 studies that met our inclusion criteria, with 14,270 patients with UC. Upadacitinib ranked highest in inducing clinical remission (99.6%), and endoscopic improvement (99.2%), followed by risankizumab (91.4%) and (82.3%) respectively. In maintenance of endoscopic improvement, upadacitinib ranked first (98.6%) followed by filgotinib 200 mg (79.2%). Risankizumab ranked first in the induction of histological remission (89.4%). Followed by guselkumab (88.3%). Upadacitinib ranked first (93.1%) in maintaining histological remission followed by guselkumab (89.5%). ConclusionUpadacitinib appears to be superior to other therapies in achieving clinical remission, endoscopic improvement and remission, and histological remission. Furthermore, novel biologics such as risankizumab and guselkumab ranked high in achieving these outcomes. This study highlights the efficacy of small molecule drugs and novel selective IL-23s as alternatives to other biologics.

Update on treatment of ANCA-associated vasculitis

This article summarizes the current guidelines and recommendations published by the European Alliance of Associations for Rheumatology (EULAR), the Kidney Disease Improving Global Outcomes (KDIGO) and the American College of Rheumatology (ACR). In addition to glucocorticoids (GC), treatment with biologics is nowadays an established option to treat Anti-Neutrophil Cytoplasmic Antibody (ANCA)-associated vasculitis (AAV). Rituximab (RTX) is used for remission induction and maintenance in organ-threatening and non-organ-threatening granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). For eosinophilic GPA (EGPA) anti-interleukin 5 (IL5) strategies are an important component of treatment for remission induction and maintenance of refractory or relapsing non-organ-threatening diseases in conjunction with GC. The dosing of GC for remission induction in GPA and MPA is now lower than was previously used and additionally, avacopan is approved as anew GC-sparing medication for GPA and MPA over 52weeks. Conventional strategies, such as cyclophosphamide (CYC) are important for remission induction in severe or refractory organ-threatening disease for all AAVs. The use of methotrexate (MTX) and azathioprine (AZA) is becoming less prominent. The most important unanswered questions in the treatment of AAVs are with respect to the duration of remission maintenance treatment and the individualized treatment guidance based on biomarkers.

An update on risk factors for relapse in antineutrophil cytoplasmic antibody-associated vasculitis.

Ongoing therapeutic advances in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) have significantly reduced the risk of death in AAV, but 30%-50% of patients still relapse. Relapse is a major problem in these diseases, leading to increased morbidity and mortality. It is, therefore, necessary to find predictors of relapse at the end of the remission induction and maintenance phases in order to personalize treatment.

Comparative Efficacy of Biologics and Small Molecule Therapies in Improving Patient-Reported Outcomes in Ulcerative Colitis: Systematic Review and Network Meta-Analysis

Abstract Background Ulcerative colitis (UC) is a chronic disorder with a considerable negative impact on health-related quality of life (HRQoL), which has been recently recognized as an important treatment target. The purpose of this study is to compare the efficacy of different biologics and small molecule therapies in achieving better patient-reported outcomes and HRQoL in patients with UC. Methods We performed a systematic review and network meta-analysis of the EMBASE, MEDLINE, and Cochrane Central databases from inception until February 1, 2024. The primary endpoint was clinical remission in the patient-reported outcome (PRO-2) score in UC patients who were treated with different biologics or small molecules during induction and maintenance phases. PRO-2 score is the sum of both stool frequency and rectal bleeding subscores. The secondary outcome was improvement of HRQoL defined as an increase in Inflammatory Bowel Disease Questionnaire score of ≥16 points from baseline or any change in total score from baseline. A random effects model was used, and outcomes were reported as odds ratio with 95% confidence interval. Interventions were ranked per the SUCRA (surface under the cumulative ranking curve) score. Results A total of 54 studies were included in the primary outcome analysis and 15 studies were included in the secondary outcome analysis. The primary analysis showed that during the induction phase all of included drugs were better than placebo in improving the PRO-2 score. Interestingly, upadacitinib was found to be superior to most medications in improving PRO-2 scores. The secondary analysis showed that guselkumab ranked first in the improvement of the Inflammatory Bowel Disease Questionnaire score, followed by upadacitinib during the induction phase. Conclusion Upadacitinib ranked first in PRO-2 clinical remission during the induction and maintenance phases. Guselkumab, mirikizumab, tofacitinib, and upadacitinib were the only novel medications that were superior to placebo in improving HRQoL in UC, with guselkumab ranking the highest, followed by tofacitinib and upadacitinib. During maintenance of remission, tofacitinib ranked highest in improving HRQoL.

Eosinophilic granulomatosis with polyangiitis: a review article

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of ANCA-associated vasculitis (AAV) within the group of small vessel vasculitides. It is defined by vasculitis of small and medium-sized vessels with granulomatous inflammation and blood and tissue eosinophilia. Almost all patients have allergic symptoms with bronchial asthma and rhinosinusitis symptoms. Further clinical manifestations vary depending on the localisation, severity, and type of disease manifestation. Eosinophilic infiltration and inflammation may result in rhinosinusitis, pneumonitis, gastrointestinal involvement, and cardiomyopathy. The latter, in particular, is associated with a poorer prognosis. As a necrotising pauci-immune small-vessel vasculitis, EGPA, similar to the other AAVs, can cause pulmonary infiltrates with alveolar haemorrhage, glomerulonephritis, cutaneous vasculitis with purpura as well as central and peripheral neurologic injuries. The presence of perinuclear ANCA (pANCA) with specificity against myeloperoxidase (MPO) is observed in approximately one-third of patients but is not specific to EGPA. MPO-ANCA-positive patients are more likely to have peripheral neurologic involvement and glomerulonephritis, whereas ANCA-negative patients are more likely to have cardiac and pulmonary involvement. What is frequently challenging in the clinical routine is to differentiate EGPA from the hypereosinophilic syndrome (HES). The therapeutic approach to EGPA depends on whether the severity of the disease is potentially organ or life-threatening. For severe forms of EGPA, acute therapy mainly includes glucocorticoids in combination with cyclophosphamide. Rituximab has come to be mentioned as an alternative treatment option in the guidelines. Various immunosuppressive therapies are available for remission maintenance. In EGPA without severe organ involvement, IL-5 blockade with mepolizumab is an approved treatment.

A Comprehensive Review of Dietary Approaches in Maintaining Remission of Inflammatory Bowel Diseases in Adults.

Inflammatory bowel disease (IBD) poses significant challenges in its management, encompassing a spectrum of conditions from Crohn's disease to ulcerative colitis. Dietary interventions have emerged as integral components of the multidisciplinary approach to IBD management, with implications ranging from disease prevention to treatment of active manifestations and addressing complications such as malnutrition. While dietary interventions show promise in improving outcomes for some patients with IBD, there is no consensus in the existing literature regarding remission maintenance in those patients. Furthermore, many patients explore dietary modifications often guided by anecdotal evidence or personal experiences and this could lead to malnutrition and decreased quality of life. This comprehensive review synthesizes existing literature to elucidate the complex interplay between diet and IBD, offering insights into the efficacy and safety of various dietary modalities in maintaining disease remission. It also highlights the importance of patient education in navigating dietary choices and potential risks associated with food avoidance, including the heightened risk of micronutrient deficiencies. Furthermore, it emphasizes the pivotal role of a multidisciplinary care team comprising clinicians and dietitians in providing personalized dietary guidance tailored to individual patient needs and goals. By synthesizing the latest evidence and providing insights into both the potential benefits and risks of dietary interventions, this review could be used as a resource for healthcare professionals and patients alike in navigating the complex landscape of dietary management in IBD.

Efficacy and Safety of Topical Tofacitinib for the Treatment of Alopecia Areata.

Alopecia areata (AA) is an autoimmune disease of the hair follicles. Although some cases resolve spontaneously, many patients require some form of treatment, including corticosteroids and vitamin D analogues, among others. Cytokine signaling in autoimmune disorders and their inhibition have been the prime objective in therapeutic research over the past few years. Janus kinase inhibitors such as tofacitinib have shown efficacy in the treatment of AA. The present study aimed to evaluate the efficacy of a novel formulation of topical tofacitinib compared to vehicle in patients with AA. A prospective, non-blinded, intrasubject vehicle-controlled study was conducted in patients with AA for a total duration of 6 months. A 2% tofacitinib citrate ointment was compounded in the pharmacy. Tofacitinib tablets (5 mg) were crushed and mixed in white soft paraffin to produce 2% ointment. A thin layer of this ointment was applied to the treatment patch, while the control patches received the application of the vehicle twice daily. Both patches in each patient were evaluated for percentage change in severity of alopecia tool [SALT] score after 24 weeks as the primary outcome. This was graded as excellent response (>50% improvement), intermediate response (25-50%), mild response (5-25%), and no response (<5% improvement). Trichoscopy and hair pull test were evaluated as secondary outcomes. The present study included 30 patients with AA having a median age of 27 years. Among 30 patients, 40% achieved excellent response (>50% change in the SALT score) over six months of treatment. The mean SALT score was significantly reduced from baseline to six months of treatment (mean [95% CI]: 4.3 [1.9-6.3]; P = 0.001). The control patch had substantially higher positive results in the final hair pull test, indicating disease activity (Treatment: 10% vs. Control: 86.7%, P < 0.001). Compared to the control patch, the prevalence of upright hair (10.0% vs. 80.0%) and terminal hair (3.3% vs. 70.0%) were significantly higher in the treatment patch (P < 0.001). No serious adverse effects were reported during the study duration. Sample size was small and the followup was not long enough to study the full effects of tofacitinib, as well as maintenance of remission or relapse after discontinuation. Topical tofacitinib proved to be an efficacious and well-tolerated treatment modality for AA with no adverse effects reported during this study.

Primary surgery versus pharmacotherapy for newly diagnosed ileocecal Crohn's disease: a hospital-based cohort study.

Limited knowledge exists regarding the optimal timing and relative advantages of primary surgery compared to medical treatment in ileocecal Crohn's disease (CD). This study aimed to compare long-term outcomes between medication-based treatment versus surgery in newly diagnosed ileocecal CD patients in an Asian population. Among the 885 patients diagnosed with CD and enrolled in the study site hospital cohort between 1980 and 2013, 93 (10.5%) had ileocecal CD. Patients were categorized into either the surgical or medical remission group based on their initial management strategy that led to remission. The rates of relapse, hospitalization, and surgery after achieving remission were compared using Kaplan-Meier curves. The numbers of patients assigned to surgical and medical remission groups were 15 (17.0%) and 73 (83.0%), respectively. The surgical remission group exhibited a lower relapse rate and longer maintenance of remission (10.7 vs. 3.7 yr; p = 0.017) during a median follow-up of 6.6 years. Hospitalization after the first remission tended to be lower in the surgical remission group (p = 0.054). No cases required repeated intestinal resection after the initial surgical remission, whereas a 23% surgery rate was reported at 5 years after initial medical treatment (p = 0.037). In the multivariable analysis, the initial medication-based treatment was significantly associated with relapse (hazard ratio = 3.23, p = 0.039). In selected cases of localized ileocecal CD, ileocolic resection might be a favorable alternative to medication- based treatment, as it demonstrates a lower relapse rate and longer maintenance of remission.

Evolving Concepts in Treat-to-Target Strategies for Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterised by a wide range of symptoms and a risk for irreversible organ damage, leading to increased morbidity and mortality. To improve long-term outcomes, innovative therapeutic goals have been explored, including attainment and maintenance of remission or low disease activity, with minimal use of glucocorticoids. Other goals encompass early diagnosis, potent yet less toxic therapies, appropriate glucocorticoid tapering, and better quality of life for the patients. Implementing a treat-to-target (T2T) approach involves treatment adjustments to achieve predefined objectives. Evidence from other chronic diseases, like hypertension and diabetes, supports the success of target-based approaches. In rheumatic diseases, the multitude of clinical features adds complexity to T2T strategies, but in rheumatoid arthritis, T2T has yielded improved outcomes. The application of T2T in SLE requires realistic therapeutic goals and practical tools for their measurement. International task forces have developed T2T recommendations for SLE, focusing on limiting disease activity, preventing organ damage, and minimising glucocorticoid use, while considering patients' quality of life. Advancements in defining clinically meaningful remission and low disease activity states, coupled with promising novel therapies, have spurred progress in the management of SLE.

Prebiotics for Induction and Maintenance of Remission in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis.

Prebiotics are nondigestible carbohydrates fermented by gut bacteria into metabolites that confer health benefits. However, evidence on their role for inflammatory bowel disease (IBD) is unclear. This study systematically evaluated the research on prebiotics for treatment of IBD. A search was performed in PubMed, Embase, Cochrane, and Web of Science. Eligible articles included randomized controlled trials or prospective observational studies that compared a prebiotic with a placebo or lower-dose control in patients with IBD. Meta-analyses were performed using random-effects models for the outcomes of clinical remission, clinical relapse, and adverse events. Seventeen studies were included. For induction of clinical remission in ulcerative colitis (UC), the fructooligosaccharide (FOS) kestose was effective (relative risk, 2.75, 95% confidence interval, 1.05-7.20; n = 40), but oligofructose-enriched inulin (OF-IN) and lactulose were not. For maintenance of remission in UC, germinated barley foodstuff trended toward preventing clinical relapse (relative risk, 0.40; 95% confidence interval, 0.15-1.03; n = 59), but OF-IN, oat bran, and Plantago ovata did not. For Crohn's disease, OF-IN and lactulose were no different than controls for induction of remission, and FOS was no different than controls for maintenance of remission. Flatulence and bloating were more common with OF-IN; reported adverse events were otherwise similar to controls for other prebiotics. Prebiotics, particularly FOS and germinated barley foodstuff, show potential as effective and safe dietary supplements for induction and maintenance of remission in UC, respectively. The overall certainty of evidence was very low. There would be benefit in further investigation on the role of prebiotics as treatment adjuncts for IBD.

#933 Serum and kidney complement and severity of ANCA associated vasculitis in the kidney

Abstract Background and Aims Kidney involvement in ANCA associated vasculitis (AAV) is commonly described as pauci-immune based on histological characteristics. However, we now know that the complement system is activated and contributes to the pathogenesis of AAV – with Avacopan (C5a inhibitor) demonstrating superior efficacy in maintenance of remission over Prednisolone in the ADVOCATE trial. Our aim was to evaluate if there is an association between kidney disease severity and the presence of serum and histological complement activation markers. Method Retrospective cohort study of 59 patients with AAV diagnosed between November 2015 and May 2019. Complement activation markers were serum complements (C3 and C4) levels and presence of complement (C3, C1q and C4) in glomerular capillary walls in immunofluorescence with intensity of 2+ and 3+. Kidney disease severity markers were peak serum creatinine value at presentation, anti-MPO or anti-PR3 levels, and number and proportion of glomeruli with crescents on kidney biopsy. Associations were evaluated using Spearman correlation or Mann Whitney U test as appropriate Results Among 59 patients with biopsy-proven AAV in the kidney, the median (25th percentile, 75th percentile) age was 68.8 (60.7, 73.4) years, serum creatinine was 263 (156, 560) µmol/L, and anti-MPO and anti-PR3 levels were 100.0 (81.5, 199.2) and 128.8 (22.9, 200) in 41 and 7 patients, respectively. respectively. The number and proportion of glomeruli with crescents were 6 (3, 12) and 33.3% (12.0%, 42.6%), respectively. Serum C3 and C4 were performed in 41 patients and the median levels were 1.00 (0.83, 1.14) and 0.24 (0.18, 0.31), respectively. Serum C3 level did not correlate with serum creatinine, anti-MPO or anti-PR3 titers, and number and proportion of glomeruli with crescents. Serum C4 level was negatively correlated with anti-MPO titer (34 patients; r = −0.393, p = 0.02) but did not correlate with serum creatinine or number or proportion of crescents. Complement in the glomerular capillary wall was present in 8 patients (13.6%): C3, C1q and C4 were present in 8, 3 and 1 patients, respectively. Serum creatinine [median 299 (IQR 133, 998) µmol/L versus 261 (156, 359) µmol/L, p = 0.39], anti-MPO titer [100 (88.3, 200) IU/ml versus 100 (79.4, 198) IU/ml, p = 0.74], number of crescents [14 (4, 21) versus 5 (3, 12), p = 0.90] and proportion of crescents [38.9% (12.5%, 42.3%) versus 31.3% (11.1%, 44.3%), p = 0.59] were not different in those with and without complement in the kidney biopsy. Conclusion The presence of complement activation markers was not associated with kidney disease severity in AAV. However, the detection of clinically significant associations may have been limited by our cohort size.

A case diagnosed with IgA nephropathy during a complete remission of minimal change nephrotic syndrome treated with rituximab.

We herein report a case of IgA nephropathy in a 20-year-old male who maintained a complete remission of minimal change nephrotic syndrome (MCNS) through the administration of rituximab (RTX). He was diagnosed with nephrotic syndrome at 4years of age. After he relapsed frequently, he was diagnosed with MCNS at 8years of age based on the findings of a kidney biopsy. At 13years of age, RTX therapy was initiated to maintain a complete remission after steroid treatment. MCNS recurred twice, including the time in which the interval between the RTX administrations was long. Whenever he relapsed, remission induction was achieved using steroids, and remission maintenance was achieved using RTX. Five months after the 7th RTX administration, the serum IgA level started to increase. After the 9th RTX administration, he demonstrated microhematuria despite the urinary protein level indicating complete remission. At the 10th administration, the urinary protein and the red-blood cell casts were also observed. A renal biopsy was performed 84months after the initial administration of RTX, and the patient was diagnosed with complications of IgA nephropathy. RTX is not considered to be a useful treatment for IgA nephropathy. The reasons for this are due to the fact that IgA1 does not decrease even following the administration of RTX, because B cells residing in the mucosa may not be deleted by RTX, and IgA production may also continue due to the presence of CD20- long-lived plasma cells. Even when administering RTX, if there are findings of glomerulonephritis on urine testing, the possibility of IgA nephropathy must be considered.