Significant Differences In Remission Rates Research Articles

Efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression or major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

To report the first and largest systematic review and meta-analysis of randomized controlled trials (RCT) to evaluate the efficacy and safety of aripiprazole or bupropion augmentation and switching in patients with treatment-resistant depression (TRD) or major depressive disorder(MDD). We conducted a systematic literature retrieval via PubMed, Embase, Web of Science, and Cochrane until April 2023 for RCT, which evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching for patients with TRD or MDD. Outcomes measured were changes in the Montgomery-Asberg Depression Rating Scale (MADRS), response and remission rate, and serious adverse events. Five RCTs, including 4480 patients, were included for meta-analysis. Among them, two RCTs were rated as "high risk" in three aspects (allocation concealment, blinding of participants and personnel and blinding of outcome assessment) because of the non-blind method, and the quality evaluation of the remaining works of literature was "low risk". Augmentation treatment with Aripiprazole (A-ARI) was associated with a significant higher response rate compared with augmentation treatment with bupropion (A-BUP) (RR: 1.15; 95% CI: 1.05, 1.25; P = 0.0007; I2 = 23%). Besides, A-ARI had a significant higher remission rate compared with switching to bupropion (S-BUP) (RR: 1.22; 95% CI: 1.00, 1.49; P = 0.05; I2 = 59%) and A-BUP had a significant higher remission rate compared with S-BUP (RR: 1.20; 95% CI: 1.06, 1.36; P = 0.0004; I2 = 0%). In addition, there was no significant difference in remission rate(RR: 1.05; 95% CI: 0.94, 1.17; P = 0.42; I2 = 33%), improvement of MADRS(WMD: -2.07; 95% CI: -5.84, 1.70; P = 0.28; I2 = 70%) between A-ARI and A-BUP. No significant difference was observed in adverse events and serious adverse events among the three treatment strategies. A-ARI may be a better comprehensive antidepressant treatment strategy than A-BUP or S-BUP for patients with TRD or MDD. More large-scale, multi-center, double-blind RCTs are needed to further evaluated the efficacy and safety of aripiprazole or bupropion augmentation and switching treatment strategies.

Comparative effectiveness of tofacitinib and tumour necrosis factor inhibitors in patients with rheumatoid arthritis in real-world practice: a prospective observational study.

To assess the effectiveness of tofacitinib vs tumour necrosis factor inhibitors (TNFi) in Korean patients with rheumatoid arthritis (RA). The study used data from a single academic referral hospital's registries of biologic disease-modifying anti-rheumatic drugs (bDMARDs) and tofacitinib and examined remission rates based on the disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) after 12 months. Multivariable logistic regression analysis was used to estimate the odds ratio (OR) for achieving remission with tofacitinib compared with TNFi, adjusting for potential confounders. This analysis included 665 patients (200 on tofacitinib and 455 on TNFi) who were followed up for at least 12 months. Of these, 96 patients in the tofacitinib group (48.0%) and 409 patients in the TNFi group (89.9%) were treatment-naïve to bDMARDs. Intention-to-treat analysis revealed no significant difference in the remission rates between the two groups (18.0% vs 19.6%, p = 0.640). Multivariable analysis demonstrated comparable remission rates with tofacitinib and TNFi (OR 1.204, 95% confidence interval [CI] 0.720-2.013). In the subpopulation naïve to JAKi and bDMARD, tofacitinib showed better remission rates than TNFi (OR 1.867, 95% CI 1.033-3.377). Tofacitinib had more adverse events (AEs) but similar rates of serious AEs (SAEs) to TNFi. In real-world settings, there was no significant difference in remission rates at 12 months between the tofacitinib and TNFi groups. In terms of safety, tofacitinib exhibited a higher incidence of AEs compared with TNFi, while the occurrence of SAEs was comparable between the groups. ClinicalTrials.gov, NCT02602704.

P514 Beyond the First Attempt: A Multi-Centre UK Analysis of Second JAK Inhibitor Use in Ulcerative Colitis

Abstract Background Tofacitinib, filgotinib, and upadacitinib are Janus Kinase inhibitors (JAKi) effective in inducing and maintaining remission in moderate-to-severe ulcerative colitis (UC). Limited data exists regarding outcomes in patients on a second JAKi after prior JAKi treatment failure. Here we describe the effectiveness of induction with a second JAKi in a cohort of UC patients. Methods In this retrospective cohort study, UC patients from 20 UK hospitals treated with a second JAKi were included. Clinical endpoints, as defined in Table 1, were assessed at week 8. Corticosteroid use, prior advanced therapies, and reason for cessation of first JAKi were documented. Results 99 patients commenced induction therapy with a second JAKi, 87% of whom had active disease by disease activity index, endoscopy or biomarkers. First JAKi was stopped due to failure or intolerance in 95% of cases. Tofacitinib was the most commonly used first JAKi (72%). Second JAKi was upadacitnib in 77% and filgotinib in 23%. There was no significant difference in the SCCAI (p=0.834) or pMayo (p=0.074) at baseline in those given either drug. Exposure to at least one other advanced therapy was seen in 78 patients, and 49 patients required steroids during induction. Both the median SCCAI and pMayo scores improved from 7 (SCCAI 5-9, pMayo 5-8) at baseline to 2 (SCCAI 0-3) and 1 (pMayo 0-3) at 8 weeks (p<0.001). Paired endoscopy results were available in 27 patients, showing an overall improvement from a median UCEIS 5 (5-6) and MES 2 (2-3) to 1.5 (0-5) and 1 (1-2.5) respectively (UCEIS p<0.001, MES p=0.019). Median faecal calprotectin reduced from 650 (331-1500) to 62 (31-173) in 45 patients (p<0.001) (figure 1B). Of the 82 patients with paired disease activity index at baseline and 8 weeks, 52% achieved clinical remission (figure 1A) of whom 93% (40/43) were in steroid-free remission, 64% (9/14) in endoscopic remission and 88% (22/25) in biochemical remission. There was no significant difference in remission rates depending on disease extent, number of previous advanced therapies, first or second JAKi, or reason for cessation of first JAKi including primary non-response (p=0.99). Serious adverse events were admission for IV steroids, colectomy and VTE (1 each), withdrawal due to adverse event n=1, zoster infections n=3. Conclusion on Our results suggest that treatment with filgotinib or upadacitinib following exposure to another JAKi can be effective in inducing clinical remission in UC. Efficacy was similar in our cohort regardless of mechanism of failure of the first JAKi or whether upadacitinib or filgotinib was used as a second JAKi. The observed safety profile was as expected especially with considerable risk of zoster infections.

Efficacy and suitability of adding short-term psychodynamic psychotherapy (STPP) to pharmacotherapy in patients with depressive disorders: a systematic review.

Recent guidelines on depressive disorders suggest a combination of antidepressants and psychotherapy in case of moderate to severe symptomatology. While cognitive behavioral therapy and interpersonal therapy are the most investigated interventions, psychodynamic psychotherapies have been less explored. The aim of this paper is to systematically review literature data on the efficacy of shortterm psychodynamic psychotherapy (STPP) in combination with antidepressants in the treatment of depressive disorders, focusing both on short and on long-term results and on potential moderators that could influence its effectiveness. The systematic review was conducted using the PRISMA guidelines. Databases searched were PubMed, Ovid, Scopus, and Cochrane Library, from inception to August 2023. Adding STPP to medications in the first six months of treatment didn't influence remission rates, but improved acceptability, work adjustment, interpersonal relationships, social role functioning, hospitalization rates and cost-effectiveness. After 12 months, a significant difference in remission rates arised, favouring combined therapy. In a long-term perspective, adding STPP to pharmacotherapy reduced the recurrence rate by almost 50%. STPP has proven to be more effective in longer depressive episodes, in more severe depressions and in patients with a childhood abuse history. Instead, STPP had no impact on major depressive disorder with comorbid Obsessive-Compulsive Disorder (OCD). Combining STPP with antidepressants appeared to be helpful both in a short-term and in a long-term perspective. Still, there are few rigorous studies with large samples and further research is needed to identify which subgroups of patients may benefit more from STPP.

In dogs with chronic enteropathy (idiopathic inflammatory bowel disease) is budesonide more effective than prednisolone or prednisone in resolving clinical signs?

PICO Question In dogs with chronic enteropathy (idiopathic inflammatory bowel disease) is budesonide more effective than prednisolone or prednisone in resolving clinical signs or improving the canine inflammatory bowel disease (IBD) activity index (CIBDAI) or the canine chronic enteropathy clinical activity index (CCECAI)? Clinical bottom line Category of research Treatment. Number and type of study designs reviewed One double-blinded randomised control trial. Strength of evidence Moderate. Outcomes reported The outcome of this study identified that no significant differences in remission rates (> 75% decrease in CIBDAI scores) were observed between the prednisone and budesonide groups. Frequency of adverse effects were also similar between the two groups. Conclusion A single study with moderate power of evidence alongside some significant limitations, particularly population size, cannot be used as the sole provider of an answer to the PICO question. As such, further studies with greater power would be required before a definitive assessment of comparative treatment efficacy can be made. How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Comparative Effectiveness of Reinduction Approaches for Pediatric Relapsed Acute Myeloid Leukemia

Introduction: Intensive frontline chemotherapy achieves initial remission rates above 80% in pediatric acute myeloid leukemia (AML), however, approximately half of patients relapse, and overall survival (OS) after relapse is poor. There is a paucity of comparative effectiveness data on salvage regimens to inform selection of optimal post-relapse therapy. The objective of this analysis was to compare outcomes following relapse by prevalent reinduction regimens in a multi-center real-world dataset. Methods: Patients 18 years and younger who had received frontline chemotherapy for AML between 2011-2019 at 12 pediatric institutions were eligible for inclusion. Trained personnel completed manual chart abstraction to obtain demographics, diagnosis, treatment, and outcome information. The analysis included patients who achieved morphologic remission and then experienced disease relapse; patients with primary refractory AML and those who pursued palliative therapy only after relapse were excluded. Prevalent reinduction regimens were classified as (1) intensive without anthracycline [e.g. fludarabine/cytarabine and high-dose cytarabine-containing regimens], (2) intensive with anthracycline (e.g. CPX-351, mitoxantrone/cytarabine and cytarabine/daunorubicin/etoposide), and (3) non-intensive (including azacytidine or decitabine-based regimens). Primary outcomes were OS after relapse and end reinduction disease response defined by morphologic remission (<5% blasts) and measurable residual disease (MRD)-negative remission (<0.1% blasts). Covariate distributions were compared by reinduction regimen using chi-square tests. Survival analyses used Kaplan-Meier methods and multivariable cox proportional hazards models. End induction response was evaluated using logistic regression. Adjustment was made for covariates found to both differ by reinduction regimen and be associated with outcome, regardless of statistical significance. Results: Of 530 patients, 157 (29.6%) experienced a relapse at a median of 9.7 months (IQR 6.5-16.3) after initial diagnosis. Median post-relapse follow-up was 2.2 years (IQR 1.1-3.2). One- and 2-year OS rates from relapse were 44.9 ± 4.1% and 38.6 ± 4.1%, respectively. Of 157 patients with relapse, 129 from 9 institutions had available information on post-relapse treatment and pursued reinduction with curative intent. Patients were 48.8% female, 27.1% Hispanic, 14.7% non-Hispanic Black and had a median age of 7.1 years (IQR 2.70-14.2) at relapse. Most patients (89.2%) relapsed after completion of frontline therapy, and 24% had undergone hematopoietic cell transplantation (HCT) in first clinical remission. Reinduction regimens were as follows: 79 (61.2%) received intensive reinduction without anthracycline, 34 (26.4%) received intensive reinduction with anthracycline and 16 (12.4%) received non-intensive reinduction. Patients with a non-intensive reinduction were more likely to have relapsed within one year of initial diagnosis (50% versus 34%, p = 0.23) and undergone transplant prior to relapse (75.0% versus 16.8%, p < 0.001). Covariates were balanced across intensive induction regimens. One-year OS was 50.3 ± 4.6%, with 63 (40.1%) achieving morphologic remission and 40 (31.0%) achieving an MRD-negativity after first reinduction cycle. Seventy-three patients (56.9%) underwent HCT after relapse; 11 (15.1%) received a second transplant. OS curves and adjusted outcome comparisons by reinduction regimen are shown in the Figure and Table. One-year OS was 51.1 ± 5.8%, 60.2 ± 9.0% and 26.7 ± 11.4% for intensive therapy without anthracycline, with anthracycline and non-intensive, respectively. However, after adjustment hazard ratios (HRs) were not statistically significant [HR = 0.85 (p = 0.65) and 1.77 (p = 0.23) for intensive with anthracycline and non-intensive, compared to non-intensive without anthracycline, respectively]. Conclusions: After controlling for patient, disease and treatment characteristics, we did not identify a significant difference in remission rates or OS by reinduction approaches for pediatric relapsed AML. Although anthracycline-based reinduction did not improve OS, adjusted point estimates suggest that anthracyclines may improve end reinduction disease response. Ongoing cohort expansion will enable comparative effectiveness analyses of specific reinduction regimens.

Modified-Release Phosphatidylcholine (LT-02) for Ulcerative Colitis: Two Double-Blind, Randomized, Placebo-Controlled Trials

The aim of this study was to evaluate the efficacy of LT-02, a novel modified-release phosphatidylcholine (PC) formulation, for induction and maintenance of remission in patients with mild to moderate ulcerative colitis (UC) and inadequate response to mesalamine. LT-02 was evaluated in a multicenter double-blind, randomized, placebo-controlled study comprising a 12-week induction trial (PCG-2), followed by a 48-week maintenance trial (PCG-4). In PCG-2, patients were randomized 1:1:1 to treatment with 0.8 g LT-02 4 times daily (QID), 1.6 g LT-02 twice daily (BID), or placebo, respectively. All patients continued to take a standard dose of oral mesalamine (≥2.4 g/day). The primary end point in PCG-2 was deep remission. Patients achieving remission at week 12 were randomly assigned 2:1:1 to 1.6 g LT-02 BID, placebo, or 500 mg mesalamine (3 times daily), respectively, in PCG-4; the primary end point was remission at 48 weeks. PCG-2 was terminated early for futility after a prespecified interim analysis; 466 patients (of 762 planned) were randomized. There was no statistically significant difference in deep remission at week 12 (placebo, 13.5%; LT-02 BID, 14.2%; LT-02 QID, 9.7%). In PCG-4, 150 patients (of approximately 400 planned) were randomized. There was no statistically significant difference in remission rates at week 48 (LT-02 BID, 49.3%; mesalamine, 50.0%; placebo, 43.2%). LT-02 was safe. Despite prior evidence of beneficial effects of PC in phase 2 trials, our induction study withLT-02 in patients with mild to moderate UC was terminated prematurely for futility. Signals of efficacy in maintenance therapy require confirmation in an adequately powered maintenance trial. LT-02 was safe and well-tolerated. gov: NCT02280629, NCT02142725.

Azathioprine vs methotrexate in eosinophilic granulomatosis with polyangiitis: a monocentric retrospective study.

To analyse the effectiveness, safety and steroid-sparing effect of AZA and MTX as induction of remission and maintenance treatment in eosinophilic granulomatosis with polyangiitis. We retrospectively collected data from 57 patients divided into four groups according to treatment: MTX/AZA as first-line agents (MTX1/AZA1) in non-severe disease or as second-line maintenance therapy (MTX2/AZA2) in severe disease previously treated with CYC/rituximab. During the first 5 years of treatment with AZA/MTX we compared the groups according to: remission rate [defined as R1: BVAS = 0; R2: BVAS = 0 with prednisone ≤5 mg/day; R3 (MIRRA definition): BVAS = 0 with prednisone ≤3.75 mg/day], persistence on therapy, cumulative glucocorticoid (GC) dose, relapse and adverse events (AEs). There were no significant differences in remission rates (R1) in each group (63% in MTX1 vs 75% in AZA1, P = 0.53; 91% in MTX2 vs 71% in AZA2, P = 0.23). MTX1 allowed R2 more frequently in the first 6 months compared with AZA1 (54% vs 12%, P = 0.04); no patients receiving AZA1 achieved R3 up to the first 18 months (vs 35% in MTX1, P = 0.07). The cumulative GC dose was lower for MTX2 vs AZA2 (6 g vs 10.7 g at 5 years, P = 0.03). MTX caused more AEs compared with AZA (66% vs 30%, P = 0.004), without affecting the suspension rate. No differences emerged in time-to-first relapse, although fewer patients treated with AZA2 had asthma/ENT relapses (23% vs 64%, P = 0.04). A significant proportion of patients achieved remission with both MTX and AZA. MTX1 had an earlier remission on a lower GC dose but MTX2 had a better steroid-sparing effect.

#4183 A PHENOTYPIC DRIVEN RITUXIMAB MAINTENANCE APPROACH IS EFFECTIVE AND SAFE IN PATIENTS WITH ANCA ASSOCIATED VASCULITIS

Abstract Background and Aims Rituximab (RTX) has emerged as the first-line treatment to maintain remission in ANCA-Associated Vasculitis (AAV). However, the ideal strategy to RTX re-dosing is still unclear [1]. Method In this monocentric and retrospective study we evaluated the efficacy and safety of two RTX-based maintenance regimens in patients with AAV. Fixed-dose (FD) RTX dosing, consisting of at least 3 pre-emptive RTX administrations every 6 months, was preferred in patients judged to be at high relapse risk. Instead, a biomarker-guided on-demand (OD) RTX dosing strategy was preferred for patients deemed at lower risk of relapse; this consisted in RTX re-treatment only in case of B-cell repopulation or rise in ANCA titer. The single patient relapse risk was assessed according to the disease phenotype (granulomatous vs vasculitic), the ANCA specificity and the disease status (onset vs relapse). Relapses were defined as increase of disease activity requiring escalation of immunosuppression; major relapses were defined in case of life/organ-threatening manifestations. Results The study included 100 patients followed for a median of 24 months (IQR 20-30), 51% treated with an OD and 49% with a FD strategy. The main baseline characteristics of our cohort are shown in the Table; patients treated with a FD strategy were more often GPA, PR3-ANCA positive, with relapsing disease and ENT involvement and less frequent renal involvement. The FD group received a median of 4 (IQR 4-4) administrations of RTX for a median cumulative dose of 2 g (IQR 2-2). Only 6 (11.8%) patients in the OD group received RTX as maintenance therapy with a median of 1 (IQR 1-3) administration of RTX for a median cumulative dose of 0.75 g (IQR 0.5-1.75). Thirteen relapses occurred, 6 in the FD group and 7 in the OD one. Remission rates were comparable in the two cohorts, with respectively 87.6% and 85.9% of the patients in remission at 24 months (Figure 1 - panel A). No significant differences in remission rates across the 2 groups were observed after considering only major flares or after stratification according to clinical diagnosis (MPA/GPA) and ANCA specificity (Figure 1 - panel B to F). Ten and 20 severe infections (p = 0.383) and 3 and 1 cancer (p = 0.581) occurred respectively in the FD and OD group. Conclusion In our case series, a phenotypic-driven approach to RTX maintenance showed comparable efficacy and safety between fixed and on-demand dosing, despite different baseline characteristics between the two groups. These results suggest that personalizing RTX maintenance may be a feasible and safe strategy.

Early Efficacy Observation of Pomalidomide-based Regimen in the Treatment of High-risk Multiple Myeloma

To investigate the efficacy and safety of pomalidomide based regimen in the treatment of high-risk multiple myeloma (MM). Clinical data of 27 high-risk MM patients treated in Shanxi Bethune Hospital from January 2021 to December 2022 were retrospectively analyzed. All patients were treated with pomadomide based regimen for at least 2 consecutive cycles, and the early therapeutic effect and safety were observed. Overall remission rate (ORR) was 63.0%(17/27 cases) and deep remission rate was 22.2%(6/27 cases) after 2 cycles of treatment; ORR was 90.5%(19/21 cases) and deep remission rate was 66.7%(14/21 cases) after 4 cycles of treatment. Both ORR and deep remission rate were significantly higher after 4 cycles of treatment than 2 cycles (P=0.044, P=0.003). Beyond that, in the newly diagnosed and relapsed refractory MM groups, ORR after 2 cycles of treatment were 75%(9/12 cases) and 60%(9/15 cases), and deep remission rates were 25%(3/12 cases) and 20%(3/15 cases), respectively; ORR after 4 cycles of treatment were 100%(9/9 cases) and 83.3%(10/12 cases), and deep remission rates were 77.8%(7/9 cases) and 58.3%(7/12 cases), respectively, while there was no significant difference in remission rates between the two groups (P>0.05). In the group of creatinine ≥177 μmol/L, the serum creatinine level was significantly decreased after 2 cycles of treatment compared with that pre-treatment (P=0.001). The 1q21 amplified subgroup accounted for the largest proportion (21/27 cases), ORR was 66.7%(14/21 cases) and deep remission rate was 23.8%(5/21 cases) after 2 cycles of treatment, ORR was 88.9%(16/18 cases) and deep remission rate was 66.7%(12/18 cases) after 4 cycles of treatment. In all the symptoms, the most common adverse reactions were pulmonary infection in 9 cases and hematological adverse reactions of grade 1-2 in 8 cases. The pomalidomide-based treatment regimen has good early curative effect on the newly diagnosed and relapsed refractory high-risk MM, and also benefits to the high-risk cytogenetic MM, or MM with renal impairment. Therefore, this treatment regimen showed a good safety, and the long-term curative effect needs to be further assessed by more clinical data.

Reoperation for Recurrent and Persistent Cushing's Disease without Visible MRI Findings.

Transsphenoidal surgery is the first-line treatment for Cushing's disease (CD), even with negative preoperative magnetic resonance imaging (MRI) results. Some patients with persistent or recurring hypercortisolism have negative MRI findings after the initial surgery. We aimed to analyze the efficacy of repeat surgery in two groups of patients and determine if there is an association between positive MRI findings and early remission. Clinical, imaging, and biochemical information of 42 patients who underwent repeat surgery by a single neurosurgeon between 2002 and 2021 was retrospectively analyzed. We compared the endocrinological, histopathological, and surgical outcomes before and after repeat surgery among 14 CD patients with negative MRI findings and 28 patients with positive MRI findings. Immediate remission was achieved in 29 patients (69.0%) who underwent repeat surgery. Among all patients, 28 (66.7%) had MRI findings consistent with solid lesions. There was no significant difference in remission rates between the recurrence and persistence groups (77.8% vs. 57.1%, odds ratio = 2.625, 95% confidence interval = 0.651 to 10.586). Patients in remission after repeat surgery were not associated with positive MRI findings (odds ratio = 3.667, 95% confidence interval = 0.920 to 14.622). In terms of recurrence, repeat surgery in patients with either positive or negative MRI findings showed reasonable remission rates. For persistent disease with positive MRI findings, repeat surgery is still an option; however, more solid evidence is needed to determine if negative MRI findings are predictors for failed reoperations for persistent hypercortisolism.

Improved Healthcare Access Reduces Requirements for Surgery in Indigent IBD Patients Using Biologic Therapy: A 'Safety-Net' Hospital Experience.

Low socioeconomic status (SES) is associated with greater morbidity and increased healthcare resource utilization (HRU) in IBD. We examined whether a financial assistance program (FAP) to improve healthcare access affected outcomes and HRU in a cohort of indigent IBD patients requiring biologics. IBD patients (>18 years) receiving care at a ‘safety-net’ hospital who initiated biologics as outpatients between 1 January 2010 and 1 January 2019 were included. Patients were divided by FAP status. Patients without FAP had Medicare, Medicaid, or commercial insurance. Primary outcomes were steroid-free clinical remission at 6 and 12 months. Secondary outcomes were surgery, hospitalization, and ED utilization. Multivariate logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI). Decision tree analysis (DTA) was also performed. We included 204 patients with 258 new biologic prescriptions. FAP patients had less complex Crohn’s disease (50.7% vs. 70%, p = 0.033) than non-FAP patients. FAP records indicated fewer prior surgeries (19.6% vs. 38.4% p = 0.003). There were no statistically significant differences in remission rates, disease duration, or days between prescription and receipt of biologics. In multivariable logistic regression, adjusting for baseline demographics and disease severity variables, FAP patients were less likely to undergo surgery (OR: 0.28, 95% CI [0.08–0.91], p = 0.034). DTA suggests that imaging utilization may shed light on surgical differences. We found FAP enrollment was associated with fewer surgeries in a cohort of indigent IBD patients requiring biologics. Further studies are needed to identify interventions to address healthcare disparities in IBD.

Efficacy of conventional-dose cytarabine, idarubicin and thioguanine versus intermediate-dose cytarabine and idarubicin in the induction treatment of acute myeloid leukemia: Long-term results of the prospective randomized nationwide AML-2003 study by the Finnish Leukemia Group.

AML-2003 study sought to compare the long-term efficacy and safety of IAT and IdAraC-Ida in induction chemotherapy of acute myeloid leukemia (AML) and introduce the results of an integrated genetic and clinical risk classification guided treatment strategy. Patients were randomized to receive either IAT or IdAraC-Ida as the first induction treatment. Intensified postremission strategies were employed based on measurable residual disease (MRD) and risk classification. Structured questionnaire forms were used to gather data prospectively. A total of 356 AML patients with a median age of 53 years participated in the study. Long-term overall survival (OS) and relapse-free survival (RFS) were both 49% at 10 years. The median follow-up was 114 months. No significant difference in remission rate, OS or RFS was observed between the two induction treatments. Risk classification according to the protocol, MRD after the first and the last consolidation treatment affected the OS and RFS significantly (p < .001). Intensified cytarabine dose in the first induction treatment was not better than IAT in patients with AML. Intensification of postremission treatment in patients with clinical risk factors or MRD seems reasonable, but randomized controlled studies are warranted in the future.

Course of Cushing`s disease and treatment outcomes in correlation with pituitary MRI in children.

Cushing's disease (CD) is a rare disorder of a persistent cortisol excess caused by ACTH-secreting pituitary tumor (corticotropinoma). Transsphenoidal surgery (TSS) is a treatment of choice for СD, which effectiveness range is from 70 to 90%. Recurrence rate after successful treatment is about 25%. If surgical treatment is unsuccessful or recurrence appear, radiation treatment is the next therapeutic option, which effectiveness range is also 90%, but the hypopituitarism rate as side effect of treatment is higher. Preoperative predictors of remission and recurrence are still unexplored what leads to further investigations. Analysis of remission and recurrence rates of pediatric CD after successful treatment according to preoperative MRI and therapeutic option. We conducted a retrospective analysis of 90 pediatric patients with CD who were observed between 1992 and 2020 at the Endocrinology Research Centre. The most common clinical symptoms of CD were weight gain [94%] and growth retardation [72%]. Pituitary tumor was detected on radiological imaging in 53/90 patients [59%], there were no signs of visible adenoma in 37/90 of patients[41%]. 63 of 90 patients underwent TSS (70%), 27 patients underwent radiosurgery (30%). Remission rate after TSS was 71%[45/63], after radiosurgery - 85% [23/27]. There were no significant differences in remission rates after radical treatment according to preoperative MRI results (P=0.21 after TSS and P=0.87 after radiosurgery, х2 analysis). Recurrence after successful treatment was diagnosed in 10 patients. There were no significant differences in time to recurrence according to preoperative MRI results (P=0.055, х2 analysis). Time to recurrence was statistically different after TSS compared to radiosurgery (P=0.007, Kaplan-Meier analysis) and in the group with developed adrenal insufficiency in the early postoperative period (P=0.04, Kaplan-Meier analysis). Analysis of side effect of treatment showed that the frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery (р&lt;0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.&gt;&lt; 0.01, Kruskel-Wallis ANOVA test). Diabetes insipidus was diagnosed only after TSS. Results of our study didn`t allow to use MRI-results as predictor of effectiveness treatment in pediatric CD. Therapeutic option has an impact on time to recurrence, not on recurrence rates. The frequency of growth hormone and gonadotrophin deficiency was statistically higher after radiosurgery compared to TSS. Further studies are needed to identify predictors of remission and recurrence in CD.

P466 Real-world effectiveness and safety of golimumab in patients with ulcerative colitis: 52-weeks of post-marketing surveillance data in Japan

Abstract Background Golimumab (GLM) is an anti-TNF-α drug approved for treating ulcerative colitis (UC). Although its efficacy and safety were well established in clinical trials, real-world evidence was still limited. In the present study, we evaluated 52-week effectiveness and safety of GLM treatment for UC based on post-marketing surveillance data. Methods The prospective, post-marketing study was conducted in 393 patients from 163 medical facilities. Patients who had been prescribed GLM were enrolled between May 2017 and September 2019 in Japan. In accordance with Japanese indication, patients received subcutaneous injections of GLM, 200 mg at week 0, 100 mg at weeks 2 and 6, followed by 100 mg every 4 weeks. Clinical remission (partial Mayo score ≤2), predictors of remission, adverse drug reactions (ADRs), and predictors of ADR development were determined at week 52. Results Of 393 enrolled patients, 391 and 386 were included in safety and efficacy analysis set, respectively (Table 1). Overall, clinical remission in the intention-to-treat population was 13.0%, 53.9%, 52.6%, 48.2%, and 43.3% at baseline (BL) and at week 6, 22, 36, and 52, respectively (Table 2). In biologic naïve group, clinical remission was 9.2%, 59.1%, 61.0%, 52.4%, and 47.0% at BL and week 6, 22, 36, and 52, respectively, while in biologic experienced group, it was 15.8%, 50.0%, 46.4%, 45.0%, and 40.5% at BL and week 6, 22, 36, and 52, respectively. At week 52, clinical remission rate in the patients who concomitantly used corticosteroid (CS) at BL was significantly lower than that in the patients who did not receive CS (p=0.017, 37.3% vs 49.2%) (Fig. 1). No significant difference in remission rate was observed between immunomodulator (IM) users and IM non-users at baseline. From multivariate analysis, concomitant use of CS (p=0.001, odds ratio [OR] =0.488, 95% CI [confidence interval] 0.314–0.759) and partial Mayo remission at BL (p&amp;lt;0.001, OR=4.329, 95% CI 2.056–9.115) were identified as independent factors associated with clinical remission. ADRs occurred in 71 patients (18.2%). The most common ADR was rash, reported in 9 patients (2.3%). Serious ADRs occurred in 40 patients (10.2%). The most frequent serious ADR was UC, reported in 8 patients (2.0%). In multivariate analysis, the presence of comorbidities was associated with ADR incidence (OR=2.000, 95% CI 1.183–3.380). Conclusion From the Japanese post-marketing data, the real-world effectiveness of GLM treatment was confirmed in both biologic naïve and experienced populations. Safety profile was generally consistent with previous findings, and no additional safety signals were identified. Concomitant use of CS, but not IM, may be likely to affect outcome of GLM therapy.

P012 Efficacy of Exclusive Enteral Nutrition and Weekly Adalimumab Combination in Crohn's Patients With Fibroinflammatory Stenosis.

Clinical remission can be achieved with exclusive enteral nutrition (EEN) in patients with Crohn's Disease with different sites of involvement, varying severity, and complications such as abscess and fistula. In the CHARM study, weekly or every other week administration of adalimumab (ADA) did not provide a significant difference in remission rates. Nevertheless, the subgroup analysis showed that in patients with anti-TNF experience, moderate-to-severely active disease, and high CRP values, rates of remission were significantly higher with weekly doses. Our aim was to determine the efficacy of EEN and weekly adalimumab combination in Crohn's patients with fibroinflammatory stenosis. Seven consecutive patients with newly diagnosed severe disease and fibro-inflammatory stenosis were included in this retrospective study. The PRO-2 score was used to assess clinical remission, the SES-CD score to determine the severity of endoscopic activity, the Nancy score to determine the severity of inflammation in tissue samples, and the MaRIA score to determine changes in magnetic resonance enterography (MRE). Nestle Modulen® (35kcal/kg) was used for twelve weeks as the EEN solution. In addition to the formulation, patients were only allowed to consume water. At the end of the 12th week, the patients gradually switched to a standard diet. Concomitantly initiated ADA was continued at 40 mg weekly after standard loading doses of 160 mg-80 mg-40 mg. The patients were evaluated with clinical and laboratory findings at the 1st, 4th and 8th weeks of the treatment, and also with colonoscopy and MRE at the 12th week. The difference between mean PRO-2 score (24.7 ± 1.97, 20.1 ± 1.63, 15.3 ± 1.81,11.4 ± 2.15, 5 ± 1.1, p = 0.031), CRP (14.3 ± 4.54, 11.2 ± 3.31, 6.92 ± 2.88, 2.16 ± 1.14, 0.25 ± 0.13, p = 0.022), albumin (2.9 ± 0.21, 3.05 ± 0.33, 3.4 ± 0.29, 4.1 ± 0.45, 4.6 ± 0.27, p = 0.044), hemoglobin (11.38 ± 0.97, 12.65 ± 0.87, 13.41 ± 0.91, 13.89 ± 0.76, 14.44 ± 0.65, p = 0.063), SES-CD score (17.14 ± 4.87, 7.66 ± 5.98, p = 0.014), MaRIA score (21.13 ± 7.42, 9.91 ± 4.55, p = 0.003) and Nancy score (3.71±0.48, 1.71±0.36, p=0.028) were all statistically significant. The stenotic segment endoscopically passed at week 12 in every patient but one, which had minimally invasive surgery (ileoascendostomy) because of ileus that developed at the eighth week of therapy. Of note, the patient who underwent surgery had perianal involvement. Despite the extremely limited number of patients and short-term follow-up results, 12-week EEN and concurrent weekly ADA therapy may be effective in inducing remission in this group of patients. There is a need for large-scale, prospective studies on this subject.

Analysis and Study on Epidemiological Features and Prognosis of Nephrotic Syndrome in Xinjiang and Heilongjiang.

Backgrounds The pathogenesis of nephrotic syndrome (NS) is complex, and there are differences between regions. This study attempted to collect clinicopathological data of patients diagnosed with NS in Xinjiang and Heilongjiang in the past 2 years, so as to explore the onset features of NS and treatment and prognosis of patients in the two regions. Methods Clinical data of 375 patients diagnosed with NS using renal biopsy in Xinjiang and Heilongjiang from March 2019 to March 2021 were collected. Clinical data of patients before treatment were collected, and the chi-square test was utilized to compare the differences in the sex distribution of two groups. The U test was utilized to compare abnormal distribution continuous data between two groups, such as age, hemoglobin, plasma albumin, proteinuria, and triglycerides. Independent sample t-test was utilized to compare normal distribution continuous data between two groups, such as serum total protein, serum creatinine, blood urea nitrogen, glomerular filtration rate, and total cholesterol. The independent sample t-test was also used to compare the immunoglobulin levels and complement levels between the two groups after treatment, including IgA, IgG, IgM, C3, and C4. Kaplan-Meier method was used to analyze and plot the cumulative curves of complete remission rate and partial remission rate. Results For 275 NS patients from Xinjiang, the male-to-female ratio was 0.81 : 1. For 84 patients from Heilongjiang, the male-to-female ratio was 1.05 : 1. The onset ages of patients in Xinjiang and Heilongjiang were 22-45 years old and 22-47 years old, respectively. Respectively, there were 221 cases (80.36%) and 66 cases (78.57%) of primary NS in Xinjiang and Heilongjiang. There were 54 cases (19.64%) and 18 cases (21.43%) of secondary NS in Xinjiang and Heilongjiang, respectively. There was no statistically significant difference in cause distribution between the two regions (p = 0.756). After treatment, immunoglobulin levels (IgA (p = 0.009), IgG (p = 0.002), IgM (p < 0.001)) and complement C3 (p < 0.001) and C4 (p < 0.001) levels in Xinjiang and Heilongjiang were statistically significant. 129 cases in Xinjiang (46.91%) and 55 cases in Heilongjiang (65.48%) were treated with glucocorticoid (GC) combined with immunosuppressive therapy, respectively. After receiving treatment, 67 (24.36%) of 275 patients in Xinjiang achieved complete remission, 166 (60.36%) achieved partial remission, 22 (26.19%) of 84 patients in Heilongjiang achieved complete remission, and 56 (66.67%) achieved partial remission, and there was no statistically significant difference in remission rate between the two regions (p = 0.159). Patients in Xinjiang and Heilongjiang achieved complete remission at an average of 10.34 weeks (9.98-10.70) and 9.95 weeks (9.26-10.65), respectively. There was no significant difference in complete remission rates between the two regions (p = 0.663). Patients in Xinjiang and Heilongjiang achieved partial remission at an average of 8.76 weeks (8.38-9.14) and 7.99 weeks (7.33-8.65), respectively. There was no significant difference in the partial remission rate between the two regions (p = 0.065). Conclusion The causes of NS in Xinjiang and Heilongjiang were similar. After treatment, there were differences in immunoglobulin levels (IgA, IgG, IgM) and complement levels (C3, C4) in the two regions. The main treatment methods used in the two regions were GC combined with immunosuppressive therapy. The prognosis of patients in the two regions was similar. The complete remission rate and partial remission rate after treatment in the two regions were similar, and the average time required to achieve complete remission and partial remission was also similar.

Electron-Dense Deposition Patterns and the Outcomes of Nephrotic Idiopathic Membranous Nephropathy Treated with Tacrolimus in Chinese Adults.

BackgroundTacrolimus may be effective in the short-term treatment of idiopathic membranous nephropathy (IMN). However, it is not clear whether an electron microscopic classification of the homogeneous and heterogeneous types of nephrotic IMN is related to the efficacy of tacrolimus in patients with IMN. This study aimed to explore this question and to provide evidence for individualized patient treatment.Material/MethodsThis 6-month retrospective study included 61 Chinese patients previously diagnosed with IMN. Patients received treatment was tacrolimus plus glucocorticoid. The patients were divided into a homogeneous group and a heterogeneous group based on the evaluation of electron-dense deposits. The initial clinicopathologic factors in the 2 groups were analyzed, and the difference in efficacy of tacrolimus in the 2 groups was assessed. The factors predicting remission were also studied.ResultsNo significant alteration in the initial clinicopathologic status was found between the 2 groups, except for proteinuria, serum albumin levels, systolic blood pressure, and renal biopsy results (stages I/II/III/IV). After 3 months of treatment, the difference in remission was not significant between the 2 groups. However, after 6 months of treatment, a significant difference in remission rates was observed between the 2 groups. The binary logistic model showed that the homogeneous nephrotic IMN was independently associated with total remission (partial plus complete remission), and was also related to complete remission.ConclusionsThe results of our study revealed that the homogeneous type of nephrotic IMN had a higher short-term remission rate and a predictive value for partial or complete remission, and it might be a meaningful marker of the short-term response to tacrolimus.

Uveitis associated with latent tuberculosis: A comparative study of the impact of antitubercular therapy combined or not with systemic corticosteroids.

To study the outcome of latent tubercular uveitis (LTBU) treated with antitubercular therapy (ATT) combined or not with adjuvant systemic corticosteroids. Twenty patients (27 eyes) with LTBU were included in a monocentric retrospective study and evaluated for the absence of active disease after treatment. Data on the clinical outcomes (active inflammation), vision (best-corrected visual acuity, BCVA) and treatment were collected retrospectively. Fourteen patients received ATT alone and six patients received ATT combined with systemic corticosteroids. The two groups were not comparable in terms of proportion of tubercular panuveitis cases and initial BCVA (59.3 ± 8.2 letters vs 44.2 ± 15.2 letters). There was no significant difference in remission rate and in BCVA between both groups 3 months after ATT discontinuation. Patients with LTBU treated with ATT alone had visual and inflammatory outcomes at least comparable to those of patients treated with ATT combined with systemic corticosteroids.

Rifampin combination therapy in staphylococcal prosthetic joint infections: a randomized controlled trial

BackgroundThe evidence supporting rifampin combination therapy in prosthetic joint infections (PJI) is limited due to the lack of controlled studies. The aim of this study is to evaluate the effect of adding rifampin to conventional antimicrobial therapy in early staphylococcal PJIs treated with debridement and retention of the implant (DAIR).MethodsIn this multicenter randomized controlled trial, 99 patients with PJI after hip and knee arthroplasties were enrolled. They were randomly assigned to receive rifampin or not in addition to standard antimicrobial treatment with cloxacillin or vancomycin in case of methicillin resistance. The primary endpoint was no signs of infection after 2 years of follow-up.ResultsForty-eight patients were included in the final analyses. There were no differences in patient characteristics or comorbidities between the two groups. There was no significant difference in remission rate between the rifampin combination group (17 of 23 (74%)) and the monotherapy group (18 of 25 (72%), relative risk 1.03, 95% confidence interval 0.73 to 1.45, p = 0.88).ConclusionThis trial has not proven a statistically significant advantage by adding rifampin to standard antibiotic treatment in acute staphylococcal PJIs.Trial registrationThe Regional Ethics Committee and the Norwegian Medicines Agency approved the study (EudraCT 2005-005494-29), and the study was registered at ClinicalTrials.gov at Jan 18, 2007 (NCT00423982).