Clinical Remission Research Articles

Dupilumab Induces Long-term On-Treatment Clinical Remission in Patients With Type 2 Asthma

Remission is proposed as a multicomponent outcome for patients with severe asthma. This post hoc analysis of QUEST (NCT02414854) and TRAVERSE (NCT02134028) evaluated whether dupilumab treatment leads to clinical asthma remission (≥12 months with no severe exacerbations, zero oral corticosteroids [OCS] use, stabilized or improved lung function, patient-reported asthma control <1.5) and assessed its durability in patients with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/μL or fractional exhaled nitric oxide ≥20 ppb at parent-study baseline) who are not on maintenance OCS. In QUEST, patients (≥12 years) were randomized to dupilumab 200/300 mg or placebo every 2 weeks (q2w) for 52 weeks. In TRAVERSE, all patients received dupilumab 300 mg q2w for up to 96 weeks. We assessed proportion of patients meeting criteria for on-treatment clinical remission up to 48 weeks of TRAVERSE. At QUEST baseline, 1040 patients receiving dupilumab and 544 on placebo had type 2 asthma; of those, 842 (dupilumab/dupilumab) and 437 (placebo/dupilumab) enrolled in TRAVERSE. At QUEST Week 52 (Year 1), 37.2% of patients receiving dupilumab met clinical remission criteria, compared with 22.2% on placebo (all P < .001). At Week 48 of TRAVERSE (Year 2 overall), 42.8% (dupilumab/dupilumab) and 33.4% (placebo/dupilumab) of patients met clinical remission criteria. Overall, 29.5% of patients in the dupilumab/dupilumab group met the criteria at both Years 1 and 2. Dupilumab treatment enabled approximately one-third of patients with type 2 asthma to meet the multicomponent endpoint for on-treatment clinical asthma remission for up to 2 years.

Is it possible to go from control to super responder to remission in asthma?

Background: Asthma, a chronic airway inflammatory disease, traditionally focuses on symptom control and minimizing complications as per asthma guidelines. Recently, the concept of achieving clinical remission has emerged as a more ambitious treatment goal. Objective: This review explores clinical remission (on and off treatment), super-responders, and complete remission (on and off treatment) in asthma. It also examines the potential of biologics in achieving clinical remission for severe asthma. Methods: A literature review on clinical remission, super-responders, and complete remission in asthma, along with biologics and remission was conducted. Results: Leading allergist/pulmonologist groups and professional societies worldwide have proposed criteria for clinical remission. Whereas core elements such as no systemic corticosteroids, no exacerbations, and stable and/or improved lung function for at least a year are generally agreed on, specific details remain under debate. U.S. guidelines incorporate stricter criteria for clinical remission. In addition, the term “super-responder” describes patients with severe asthma and with major quality-of-life improvements after receiving biologics. Despite limited studies, biologics seem to produce remission rates (20‐40%), depending on the criteria used. Conclusion: A universally accepted definition for clinical remission in asthma remains under development. The concept of super-responder requires further investigation in research and clinical settings. Whereas early studies show promise, biologic therapies, although revolutionary for severe asthma treatment, do not guarantee clinical remission for most patients.

On-Treatment Clinical Remission of Severe Asthma With Real-World Longer-Term Biologic Use

BackgroundThere are limited real-world data describing the proportion of patients with severe asthma (SA) who achieve on-treatment clinical remission with long-term biologic treatment. ObjectiveTo examine the proportion and characteristics of adults with SA who achieved clinical remission with biologic therapy. MethodsCHRONICLE is an observational study of US subspecialist-treated adults with SA. Sites reported exacerbations and biologic use from 12 months prior to enrollment forward. Monthly Asthma Control Test (ACT) scores and 6-monthly specialist assessments of asthma control were collected. Patients enrolled from February 2018–February 2023 with biologic initiation during the study observation period and continued use for ≥12 months were evaluated. Incident on-treatment clinical remission was defined in a 12-month interval as the absence of exacerbations and systemic corticosteroid (SCS) use, ≥50% of ACT scores ≥20 in the latest 6 months, and specialist report of asthma control. ResultsAmong evaluable patients (N=611), median duration of biologic use was 39.6 months. In at least one 12-month interval during the study, 79.9% of patients had no exacerbations or SCS use, and 46.0% met the definition of clinical remission at any point. The point prevalence of clinical remission increased from 22.3% at 12–13 months of biologic use to 34.3% at 47–48 months of biologic use. ConclusionsIn a real-world cohort of patients with SA with longer-term biologic treatment, almost one-half achieved on-treatment clinical remission. With a year or more of biologic therapy, clinical remission is a feasible treatment goal in SA.

Evaluation of the Symptoms and Clinical Characteristics of Crohn's Disease and Ulcerative Colitis That Affect Healthcare Providers' Treatment Choices.

Treatment of inflammatory bowel disease-Crohn's disease (CD) and ulcerative colitis (UC)-is dependent on healthcare providers' (HCPs') clinical assessment of patient symptoms. We therefore evaluated which CD and UC symptoms impact HCPs' treatment choices and assessed the impact of those symptoms on treatment decision-making. We also examined the role of complete control (mucosal/histologic healing, clinical remission, no bowel urgency) in treatment decision-making, considerations for dose escalation or switching treatments, and HCPs' willingness to use the Urgency Numeric Rating Scale (NRS) to assess bowel urgency severity. We conducted an observational, cross-sectional, self-administered survey among HCPs (N = 459, across types/specialties) who work in direct patient care and treat patients with CD and UC in the United States. Data were collected from eligible participants between November 21, 2022, and December 6, 2022, and responses were summarized through descriptive statistics. For CD and UC, the symptoms of greatest importance when deciding on the course of treatment included cramping or abdominal pain, rectal bleeding, diarrhea, anemia, weight loss, and bowel urgency. Furthermore, most HCPs ranked rectal bleeding, clinical remission, abdominal pain, and complete control as "very" to "extremely" important in decisions about the course of treatment, dose escalation, or switching treatments. In total, 22.9% of HCPs indicated that they use the Urgency NRS, while 89.3% were at least somewhat willing to use it in the future. Our study provides real-world insights into the symptoms and clinical characteristics that most impact HCPs' treatment choices for CD and UC in clinical practice.

Placebo rates in Crohn’s disease randomized clinical trials: An individual patient data meta-analysis

Understanding placebo rates is critical for efficient clinical trial design. We assessed placebo rates and associated factors using individual patient data (IPD) from Crohn's disease (CD) trials. We conducted a meta-analysis of phase 2/3 placebo-controlled trials evaluating advanced therapies in moderate-to-severe CD (2010-2021). Deidentified IPD were obtained through Vivli Inc. and Yale University Open Data Access Project. Primary outcomes were clinical response and remission. Pooled placebo rates and 95% confidence intervals (CIs) were estimated using one- and two-stage meta-analytical approaches. Regression analyses identified patient-level factors associated with placebo rates. Using IPD from eight induction (n=1147) and four maintenance (n=524) trials, overall placebo clinical response and remission rates for induction were 27% (95%CI=23-32%) and 10% (95%CI=8-14%) respectively, and 32% (95%CI=23-42%) and 22% (95%CI=14-33%) for maintenance, respectively. Among bio-naïve patients, placebo response and remission rates during induction were 29% (95%CI=24-35%) and 11% (95%CI=8-15%) respectively, and 26% (95% CI=20-33%) and 10% (95% CI=8-14%) for bio-exposed, respectively. During maintenance, bio-naïve response and remission rates were 41% (95%CI=34-48%) and 32% (95%CI=24-40%), respectively, and 29% (95%CI=24-34%) and 16% (95%CI=13-21%) for bio-exposed, respectively. Higher baseline C-reactive protein concentration predicted lower placebo rates, while higher baseline albumin levels and body mass index increased the odds of placebo outcomes. Increased baseline Crohn's Disease Activity Index and 2-item patient-reported outcome scores predicted higher response rates in induction, lower response rates in maintenance, and lower remission rates in induction and maintenance. Patient- and trial-level characteristics influence placebo rates in CD trials. Careful implementation of eligibility criteria, outcome definitions, and patient stratification may reduce placebo rates.

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

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

S1472 Efficacy of Risankizumab Maintenance Therapy by Clinical Remission and Endoscopic Improvement Status in Patients With Moderately to Severely Active Ulcerative Colitis: Post Hoc Analysis of the COMMAND Phase 3 Study

S1472 Efficacy of Risankizumab Maintenance Therapy by Clinical Remission and Endoscopic Improvement Status in Patients With Moderately to Severely Active Ulcerative Colitis: Post Hoc Analysis of the COMMAND Phase 3 Study

Reactive Immunomodulator Addition to Infliximab Monotherapy Restores Clinical Response in Inflammatory Bowel Disease: A Meta-Analysis.

Patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) commonly experience immunogenic loss of response (LOR) by formation of anti-drug antibodies (ADAs). An immunomodulator (IMM) used in combination with initial IFX induction is known to reduce ADA development and improve clinical outcomes. We aimed to assess the impact of reactively adding an IMM to patients on IFX monotherapy. We conducted a retrospective cohort study and systematic review with meta-analysis of patients with IBD demonstrating immunologic LOR, with or without clinical LOR, that had an IMM (azathioprine, 6-mercaptopurine, or methotrexate) reactively added (reactive combination therapy; rCT) to combat elevated ADAs and raise IFX level. Data were extracted for pooled effect size estimation using random-effects models, and ADA and IFX trough levels were compared pre- and post-IMM initiation. We identified 6 patients who received rCT due to rising ADA titers and low IFX levels. Median ADA titer decreased from 506ng/mL (interquartile range (IQR) [416-750]) to 76.5ng/mL (IQR [25.8-232]), an 85% decrease (p = 0.031). Median IFX trough increased from 0.4µg/mL (IQR [0.4-0.48]) to 8.25µg/mL (IQR [3.7-9.6]), a 20.6-fold increase (p = 0.038). Meta-analysis pooled effect size of 7 studies with 89 patients showed an 87% ADA titer reduction [95% confidence interval (CI) = 72-94%], 6.7-fold increased IFX trough (95% CI = 2.4-18.7), and 76% clinical remission rescue rate (95% CI = 59-93%). These results suggest rCT is a valid rescue strategy in patients with immunogenic LOR to IFX to reduce ADA titers, restore therapeutic IFX levels, and recapture clinical remission of IBD.

Effect of Dupilumab on Radiological Remission in Patients with Chronic Rhinosinusitis with Nasal Polyp: A One Step Forward Toward Clinical Remission.

While achieving complete radiological improvement in patients with nasal polyps is often observed following surgical resection, the impact of biologic therapy, specifically dupilumab, on polyp size is an area of great interest. The objective of this study was to assess the effect of dupilumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) by assessing nasal polyps using the computed tomography (CT) staging system, Lund-Mackay score (LMS). A two-year prospective cohort study was conducted on 29 patients diagnosed with CRSwNP and asthma and eligible for dupilumab as an add-on therapy. The study involved comprehensive assessments of patients before biologic initiation and after the study. These assessments included clinical, laboratory, and radiological evaluations. Dupilumab treatment reduces LMS across sinuses (p<0.001) and improves nasal obstruction (p=0.001). Blood eosinophil count (BEC) predicts persistent sinus obstruction, doubling the likelihood per unit increase (odds ratio: 1.67, p=0.02). BEC levels identify persistent nasal obstruction (AUC: 76%, p=0.04), with a cutoff point above 255.5 cells per microliter, revealing a sensitivity of 100% and a specificity of 42%. The probability of persistent nasal obstruction at the 20th month is 55%, regardless of prior nasal polyp surgery (p=0.41). Dupilumab led to significant radiological improvements in patients with CRSwNP, demonstrating a potential role of radiological remission, irrespective of prior nasal polyp surgery. Additionally, BEC levels may guide the likelihood of persistent nasal obstruction.

Comparative Efficacy and Safety of Upadacitinib vs. Vedolizumab, Ustekinumab, and Tofacitinib After Induction and Maintenance for Ulcerative Colitis: Three Matching-Adjusted Indirect Comparisons.

Evidence on the comparative efficacy and safety of approved therapies for ulcerative colitis (UC) during induction and maintenance, including upadacitinib (UPA), vedolizumab (VEDO), ustekinumab (UST), and tofacitinib (TOFA), is limited. Using data from phase 3 trials, three placebo (PBO)-anchored matching-adjusted indirect comparisons of the efficacy and safety of UPA versus VEDO, UST, and TOFA (U-ACHIEVE and U-ACCOMPLISH, GEMINI-1, UNIFI, and OCTAVE induction and maintenance trials) have been conducted. Baseline characteristics from UPA trials were weighted separately to match each comparator trial. Induction responders were re-randomized to oral UPA 15 or 30mg, VEDO 300mg intravenously every 8weeks (Q8W), UST 90mg SC Q8W, or oral TOFA 5mg, or PBO in maintenance. Treat-through efficacy outcomes at weeks 44(UST)/46(VEDO)/52(UPA/TOFA) were adjusted by the likelihood of induction response and included clinical response, clinical remission, and endoscopic improvement. Safety outcomes included adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation (except UPA vs. VEDO). Benefit-risk was assessed by numbers needed to treat (NNT)/harm, calculated as the inverse of the difference in proportions of patients achieving each efficacy/safety outcome for UPA versus comparator. The proportions of patients who demonstrated clinical response or endoscopic improvement was greater with UPA 15mg versus VEDO and TOFA (p<0.05). The proportions of patients demonstrating all treat-through efficacy outcomes were significantly greater with UPA 30mg versus VEDO, UST, or TOFA with NNTs 3.2-8.7. No significant differences in proportions of AEs, SAEs, and AEs leading to discontinuation were observed between the two doses of UPA and comparators. In patients with active UC, greater clinical efficacy, and similar safety after 1year of maintenance were observed with UPA versus VEDO, UST, and TOFA, suggesting a favorable benefit-risk profile for UPA. Despite matched baseline characteristics, differences in trial design and endpoints may persist.

Long-term remission of Hailey-Hailey disease by Er:YAG ablative laser therapy.

Hailey-Hailey disease (HHD) is a rare genetic therapy-resistant blistering disease with great disease burden. Treatment is currently focused on symptomatic relief. Er:YAG ablative laser therapy is a therapeutic modality with promising results, though evidence is currently scarce. To analyse the effect of Er:YAG ablative laser therapy on clinical remission of erosive plaques in HHD and on patient's quality of life (QoL). In this observational study eight patients were included and 77 erosive plaques were treated once only by Er:YAG laser and assessed for clinical remission. QoL was evaluated by obtaining Skindex-29 and DLQI questionnaires before laser therapy, 6 weeks and 3 years after laser therapy. Skin biopsies were taken to evaluate the depth of laser ablation. The intercellular distance between keratinocytes, the number of desmosomes and intermediate filament distribution were studied by electron microscopy before and after laser therapy and in clinically uninvolved skin and were compared to subjects without HHD. One single Er:YAG laser ablation to mid-dermis resulted in complete remission of 97.4% of HHD plaques (75/77) after median 38 months (range 7-63 months) and significantly improved QoL. Laser therapy restored the number of desmosomes, decreased intercellular distance and diminished perinuclear retraction of keratin filaments to a level comparable to the patient's clinically uninvolved skin. After laser ablation, the skin showed significantly fewer ultrastructural aberrations compared to the patient's clinically uninvolved skin and rather resembled the skin of healthy control individuals. One single Er:YAG laser treatment resulted in long-term remission of HHD and significantly improved QoL. Our findings support a greater role for ablative laser surgery in the management of this recalcitrant disorder.

Clinical outcomes analysis of image-guided brachytherapy as definitive treatment for inoperable endometrial cancer

ObjectivesThis study evaluates the efficacy and toxicity of image-guided brachytherapy combined with or without external beam radiotherapy (IGBT ± EBRT) as definitive treatment for patients with inoperable endometrial cancer (IOEC), in addition to establishing a risk classification to predict prognosis.MethodsFifty-one IOEC patients who underwent IGBT ± EBRT at Peking Union Medical College Hospital from January 2012 to December 2021 were retrospectively analyzed, of which 42 patients (82.4%) were treated with IGBT + EBRT and 9 patients (17.6%) with IGBT alone. Establishing risk classification based on FIGO 2009 staging and biopsy pathology, stage III/IV, non-endometrioid, or Grade 3 endometrioid cancer were included in the high-risk group (n = 25), and stage I/II with Grade 1–2 endometrioid cancer was included in the low-risk group (n = 26).ResultsThe median follow-up time was 58.0 months (IQR, 37.0–69.0). Clinical complete remission (CR) was achieved in 92.2% of patients after radiotherapy (n = 47). The cumulative incidences of locoregional and distant failure were 19.6% (n = 10) and 7.8% (n = 4), respectively. A total of 20 patients died (39.2%), including 10 cancer-related deaths (19.6%) and 10 comorbidity-related deaths (19.6%). The 5-year locoregional control (LRC), time to progression (TTP), overall survival (OS), and cancer-specific survival (CSS) were 76.9%, 71.2%, 59.4%, and 77.0%, respectively. No Grade 3 or above acute or late toxicities were reported. In univariate analysis, LRC, TTP, and CSS were significantly higher in the low-risk group than in the high-risk group (P < 0.05). After adjusting for age, number of comorbidities, radiotherapy modality, and chemotherapy, the low-risk group was still significantly better than the high-risk group in terms of LRC (HR = 6.10, 95% CI: 1.18–31.45, P = 0.031), TTP (HR = 8.07, 95% CI: 1.64–39.68, P = 0.010) and CSS (HR = 6.29, 95% CI: 1.19–33.10, P = 0.030).ConclusionsIGBT ± EBRT is safe and effective as definitive treatment for IOEC patients, achieving satisfactory locoregional control, favorable survival outcomes, and low toxicity. Risk classification based on FIGO 2009 staging and biopsy pathology is an independent prognostic factor for LRC, TTP, and CSS.

S1470 Matching-Adjusted Indirect Comparison of Etrasimod Versus Ozanimod for Clinical Response and Remission Among Patients With Moderately to Severely Active Ulcerative Colitis

S1470 Matching-Adjusted Indirect Comparison of Etrasimod Versus Ozanimod for Clinical Response and Remission Among Patients With Moderately to Severely Active Ulcerative Colitis

S1200 Sustained Efficacy and Safety After 5 Years of Continuous Ozanimod Treatment Independent of Clinical Remission Status: An Interim Analysis of the True North Open-Label Extension Study

S1200 Sustained Efficacy and Safety After 5 Years of Continuous Ozanimod Treatment Independent of Clinical Remission Status: An Interim Analysis of the True North Open-Label Extension Study

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.

Real-world experience of vedolizumab use in Colombian patients with inflammatory bowel disease—EXVEDOCOL

BackgroundReal-world studies about the effectiveness and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD) in Latin America are scarce. Our study describes the effectiveness and safety of VDZ in Colombian patients with IBD. MethodsEXVEDOCOL (EXperience of VEDOlizumab in COLombia) was a retrospective, multicenter, observational study. Adults with IBD receiving a first dose of VDZ between July 2016 and October 2018 were included. The co-primary outcomes clinical response, and remission, were determined at week 14 and last visit during the maintenance phase (LVMP). The secondary outcomes, deep remission and loss of response were recorded at LVMP. ResultsThirty-one patients (25 ulcerative colitis (UC), 6 Crohn's disease (CD)) were included. At week 14, clinical response was achieved by 87.1% (27/31) of the patients treated with VDZ, while loss of response was reported in 6.7% (2/30). The remission rate at week 14 was 65.5% (19/29) and 75.9% (22/29) at LVMP. Prior anti-TNF exposure was reported in 61.3% (19 patients) of whom 84.2% (16/19) achieved clinical response at week 14 and 89.5% (17/19) at LVMP. For anti-TNF naïve patients, clinical response was recorded in 91.7% (11/12) at week 14 and 100% (12/12) at LVMP. ConclusionsHigh clinical remission rates and safety profile highlight VDZ as a valuable treatment option for IBD patients. Anti-TNF naïve patients may derive greater benefit from therapy. Studies with larger cohorts could confirm these findings.

Safety and efficacy of stem cell therapy for Crohn's disease: An umbrella review of systematic reviews.

Crohn's disease is a chronic, relapsing form of inflammatory bowel disease marked by severe gastrointestinal inflammation and a broad range of debilitating symptoms. Despite advances in medical treatments, achieving sustained remission remains challenging for many patients. This umbrella review aims to consolidate evidence from various systematic reviews to evaluate the efficacy and safety of stem cell therapies in treating Crohn's disease. This review followed the Joanna Briggs Institute methodology and adhered to PRISMA guidelines. A literature search of PubMed, Web of Science, Embase, and the Cochrane Library covered records up to April 20, 2024. Only systematic reviews and meta-analyses on stem cell therapy for Crohn's disease were considered. Data were extracted and analyzed for clinical efficacy indicators like remission induction and safety metrics, including adverse events and mortality rates. Sixteen systematic reviews were included, spanning studies conducted between 2009 and 2023. Stem cell therapy showed a pooled risk ratio (RR) of 1.299 (95% CI: 1.192 to 1.420) for clinical remission, indicating a 29.9% increased likelihood of remission compared to controls. The pooled RR for healing perianal Crohn's disease was 1.358 (95% CI: 1.13 to 1.631), suggesting a 35.8% increased likelihood of healing. A pooled RR of 1.481 (95% CI: 1.036 to 2.116) shows a 48.1% higher immediate fistula closure rate with stem cell therapy. For long-term outcomes, a RR of 1.422 (95% CI: 1.091 to 1.854) indicates a 42.2% increased likelihood of maintaining closure. However, stem cell therapy did not significantly impact Crohn's Disease Activity Index (CDAI) (RR: 1.154, 95% CI: 0.193 to 6.883) and Perianal Disease Activity Index (PDAI) scores (mean difference at 12 weeks: -0.505, 95% CI: -2.481 to 1.471; mean difference at 24 weeks: -0.338, 95% CI: -1.638 to 0.963). The safety profile was comparable to conventional therapies, with a pooled RR of 0.972 (95% CI: 0.739 to 1.278) for adverse events and 1.136 (95% CI: 0.821 to 1.572) for serious adverse events. Stem cell therapy offers significant progress in treating Crohn's disease, particularly in complex cases, by improving fistula closure rates and suggesting potential as a supplementary therapy. Its safety profile aligns with conventional treatments, yet ongoing clinical trials are crucial to optimize its use. Continual research will enable healthcare providers to tailor more effective treatment strategies for this challenging condition.

In persistent uncontrolled asthma, adding azithromycin to standard therapy increased clinical remission rates at 1 y.

Thomas D, McDonald VM, Stevens S, et al. Effect of azithromycin on asthma remission in adults with persistent uncontrolled asthma: a secondary analysis of a randomized, double-anonymized, placebo-controlled trial. Chest. 2024;166:262-270. 38431051.

INTEREST OF REGULAR ASSAYS OF AQUEOUS HUMOR INTERLEUKIN-10 LEVELS IN MONITORING OF VITREORETINAL LYMPHOMA.

To investigate the variation of interleukin-10 (IL-10) levels in the aqueous humor (AH) of patients with vitreoretinal lymphoma (VRL) throughout therapy and follow-up and analyze the relation of these variations with VRL clinical course and relapse. This study retrospectively included consecutive patients diagnosed with VRL in a single center. AH IL-10 samples and patient clinical course were evaluated. The response to treatment was evaluated according to the criteria set by the International Primary Central Nervous System Lymphoma Collaborative Group. A total of 59 eyes of 34 patients were included. Interleukin-10 levels decreased significantly at first AH sample after therapy induction (median [IQR] 3.0 [2.8-3.6] months) among patients in complete clinical remission (P < 0.001). Among patients in complete clinical remission with residual detectable IL-10 in AH after therapy induction (85.3% systemic chemotherapy, 11.8% intravitreal methotrexate, 2.9% palliative care), 87.5% experienced ocular relapse within 5 years. The detection of IL-10 in AH at the first visit after induction for complete clinical remission obtained a sensitivity of 77.8% (95% CI 0.45-0.96) and a specificity of 96.4% (95% CI 0.82-0.99) to predict ocular relapse. For relapsing eyes (N = 26), IL-10 significantly increased between the last IL-10 measurement and the time of the first ocular relapse (P < 0.001). In 76.0% of cases, an increase in IL-10 was detected earlier than clinical relapse with a mean (SD) of 4.0 (2.4) months. The present study suggested the usefulness of IL-10 in the prognosis of VRL. This study showed a relation between IL-10 in AH and tumoral activity, and for the first time with disease relapse.

Persistence of subcutaneous versus intravenous infliximab in a real-life cohort: A propensity-score matched comparative analysis

BackgroundThere is limited comparative data on patients with inflammatory bowel disease (IBD) switched from intravenous to subcutaneous infliximab and those continuing intravenously. This study aimed to compare the persistence and tolerance of subcutaneous and intravenous infliximab and the outcomes of patients resuming intravenous infliximab. MethodsWe conducted a retrospective single-centre cohort study involving IBD patients treated with maintenance intravenous infliximab. The switch to subcutaneous infliximab was offered to patients in clinical remission receiving an intravenous dose ≤ 10 mg kg-1 every ≥ 6 weeks. The switch group was compared to controls remaining on intravenous infliximab due to refusal of the switch. ResultsWith a median follow-up of 59 (46–67) weeks, subcutaneous infliximab was discontinued in 28/282 (10 %) patients and intravenous infliximab in 1/78 (1 %) patient (p = 0.01); after propensity score-matching of the two cohorts, persistence rates at 52 weeks were respectively 91 % (95 % CI 84–98) and 100 % (95 % CI 100–100, p = 0.01). Among the 28 who discontinued subcutaneous infliximab, 27 resumed intravenous infliximab, with 4 (1 % of the switch group) who permanently stopped infliximab. ConclusionSwitching from intravenous to subcutaneous infliximab led to a lower treatment persistance. In cases of poor tolerance or relapse under subcutaneous infliximab, resuming intravenous infliximab is effective.