Predictive Factors For Treatment Response Research Articles

#622 Baseline inflammatory indexes and clinicopathological features to predict the outcome of acute interstitial nephritis

Abstract Backgrounds-and-aims Acute tubulointerstitial nephritis(AIN) is a rare cause of acute kidney injury(AKI). We aimed to investigate the characteristics of AIN patients and predictive factors for treatment response. Method 31 patients diagnosed with AIN by biopsy between 2006-2021 were included in this retrospective study. Baseline clinical, pathological, and laboratory findings, including CBC(complete blood count), creatinine, serum-immune-inflammation-index(SII), neutrophil-to-lymphocyte ratio(NLR), and platelet-to-lymphocyte ratio(PLR) were evaluated. Also, treatment response and creatinine levels at the last follow-up were noted. Results Median age was 46 years, and 80.6% of the patients were female. Median baseline creatinine and proteinuria levels were 4.1 mg/dL and 0.84 g/g or g/day. Median follow-up was 14 months. 93.5% of patients received immunosuppressives. End-stage-kidney-disease(ESKD) developed in five patients. Renal recovery(creatinine < 1.4 mg/dL) was observed in 17 (54.8%) patients. Global glomerulosclerosis percentage, interstitial fibrosis(IF), tubular atrophy(TA), granuloma formation, and higher baseline hemoglobin levels were associated with poor renal outcomes(non-responder). Also, ESKD-developed patients had higher baseline hemoglobin(p = 0.033) and lymphocyte(p = 0.044) and lower PLR levels(p = 0.016), as well as higher degrees of global glomerulosclerosis(p = 0.014), IF(p = 0.042), and TA(p = 0.030). Conclusion Treatment rates are low for AIN, which may lead to ESKD. Besides chronicity in pathology specimens, higher baseline hemoglobin levels and lower PLR might be prognostic for AIN. Further studies should be conducted on new markers for AIN.

Prediction model for treatment response of primary membranous nephropathy with nephrotic syndrome.

To investigate the predictors and establish a nomogram model for the prediction of the response to treatment in primary membranous nephropathy (PMN) with nephrotic syndrome (NS). The clinical, laboratory, pathological and follow-up data ofpatients withbiopsy-proven membranous nephropathy at the Affiliated Hospital of QingdaoUniversity were collected. A total of 373 patients were randomly assigned into development group (n = 262) and validation group (n = 111). Logistic regression analysis was performed in the development group to determine the predictors of treatment response. A nomogram model was established based on the multivariate logistic regression analysis and validated in the validation group. The C-index and calibration plots were used for the evaluation of the discrimination and calibration performance, respectively. Serum albumin levels (OR = 1.151, 95% CI 1.078-1.229, P < 0.001) and glomerular C3 deposition (OR = 0.407, 95% CI 0.213-0.775, P = 0.004) were identified as independent predictive factors for treatment response in PMN with NS, then a nomogram was established combining the above indicators and treatment regimen. The C-indices of this model were 0.718 (95% CI 0.654-0.782) and 0.789 (95% CI 0.705-0.873) in the development and validation groups, respectively. The calibration plots showed that the predicted probabilities of the model were consistent with the actual probabilities (P > 0.05), which indicated favorable performance of this model in predicting the treatment response probability. Serum albumin levels and glomerular C3 deposition were predictors for treatment response of PMN with NS. A novel nomogram model with good discrimination and calibration was constructed to predict treatment response probability at an early stage.

Efficacity and Safety of the Fluocinolone Acetonide Implant in Uveitic Macular Edema: A Real-Life Study from the French Uveitis Network.

To evaluate the safety and efficacy of the fluocinolone acetonide implant (FAi, Iluvien® Horus pharma, Nice, France) in non-infectious uveitic macular edema (UME) and to approach the predictive factors of treatment response. This retrospective, multicenter real-life study included patients with chronic non-infectious UME who received intravitreal FAi after at least two dexamethasone implants (DEXi). Twenty-six eyes from 22 patients (73.1% of females) were included. The mean age was 60.4 ± 16 years. The mean follow-up was 11.4 ± 2 months. The mean baseline best-corrected visual acuity (BCVA) was 0.43 ± 0.36 LogMAR, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). The mean baseline central macular thickness (CMT) was 429 ± 110 μm, improving significantly after 1, 3, 6 and 12 months (all p < 0.05 vs. baseline). Five eyes (19.2%) developed ocular hypertension during the follow-up, requiring initiation or strengthening of intraocular pressure lowering medication. The majority of eyes (77%) did not require any rescue DEXi during the available 12-month follow-up. The resolution of UME after DEXi seemed to predict the anatomical response after FAi. The baseline presence of a disorganization of the inner retinal layers (DRIL) and hyperreflective foci (HRF) were both associated with a higher likelihood of requiring rescue DEXi injections. FAi implantation led to a significant BCVA and CMT improvement with a good safety profile over the 12-month follow-up. Predictive factors of treatment outcomes seem to include the anatomical response to DEXi and the presence of DRIL and HRF at baseline.

P518 Dietary and non-dietary predictors of treatment response to adalimumab in anti-TNFα-naïve adults with Crohn’s disease

Abstract Background Biologics, such as anti-TNFα agents, are commonly used in the management of Crohn’s disease (CD). A significant proportion of patients do not respond to treatment, necessitating the exploration of pre-treatment predictors of treatment response. Methods Anti-TNFα-naïve adults with active CD (Crohn’s Disease Activity Index; CDAI≥150) participating in an RCT (NCT04859088) were randomised to receive adalimumab monotherapy or adalimumab combination therapy with 50% partial enteral nutrition (PEN). Treatment response (CDAI&amp;lt;150) was assessed after 6 weeks, baseline diet was assessed with EPIC-Norfolk FFQ, alternative Mediterranean diet scores (aMED), and principal component analysis (PCA) with orthogonal (varimax) rotation was used to identify data-derived dietary patterns. Baseline predictors evaluated included PEN use, steroid use, immunomodulator use, age, disease duration, CDAI, C-Reactive protein (CRP), albumin, haemoglobin, Scottish Index of Multiple Deprivation (SIMD) score, adherence to dietary patterns identified, aMED score, smoking status, alcohol consumption, physical activity level, body mass index (BMI), fat mass (kg/m2), fat-free mass (kg/m2), and handgrip strength. Differential analysis between responders and non-responders was carried out with general linear model or chi-square test when appropriate. Random forest model with recursive feature elimination (RF-RFE) was used to identify the most predictive factors of treatment response. Results Of 42 participants recruited to the study, 62% (26) responded to treatment. PCA revealed four dietary patterns (Figure 1A). Responders to adalimumab were younger (mean (SD): 36.0 (17.1) vs 50.8 (10.0), P=0.004), had lower baseline CDAI (mean (SD): 228 (62) vs 286 (78), P=0.018), higher CRP (14.5 (19.2) vs 4.6 (5.8) mg/L, P=0.036), were less likely to smoke (31% (5 of 16) vs 8% (2 of 26), and less likely to adhere to a dietary pattern characterised by high consumption of animal products (PC2) (P=0.030). Adherence to PC2 also correlated positively with age (r=0.327, P=0.035). The RF-RFE algorithm highlighted young age, low baseline CDAI and low PC2 adherence as key factors (Sensitivity: 77%, Specificity: 63%, PPV: 77%, NPV: 63%, OOB: 29%, P=0.012) (Figure 1B). Interestingly, exclusion of dietary factors improved diagnostic performance of the model (Sensitivity: 77%, Specificity: 75%, PPV: 83%, NPV: 67%, OOB: 24%, P=0.003) (Figure 1C), indicating potential interactions by other factors like age. Conclusion Young age, non-smoking, low baseline CDAI and elevated CRP predict adalimumab response in anti-TNFα-naïve adults. While dietary factors may also play a role, their impact seems confounded by other non-dietary factors. Further research is warranted in this area.

Dynamics of Virological and Clinical Response Parameters of Bulevirtide Treatment for Hepatitis D: Real-World Data

Background and aimsThe entry inhibitor bulevirtide represents the first specific treatment for Hepatitis-D-virus (HDV)-infected patients. In clinical trials, around 80% of patients achieve normalization of alanine aminotransferase (ALT) with about 60% virological response after one year, but little is known about the dynamics of responses and clinical predictors of treatment outcomes. We report our single-center data from 15 patients and describe response dynamics, clinical outcomes and predictive factors for treatment response. MethodsRetrospective data from 15 patients have been analyzed at our department who started treatment with bulevirtide between 10/2020 and 08/2022. According to our standard procedures laboratory parameters were controlled monthly; transient elastography was performed every three months, treatment duration was twelve months. ResultsTreatment response rates after one year of treatment were similar to published data from clinical trials. ALT normalization usually occurs between month 2-6 of treatment, followed by a virological response after ≥ 6 months. Patients with more severe hepatitis at treatment start were less likely to respond in the first year of treatment. Loss of HDV-RNA was observed for one third of patients after ≥1 year of treatment. Low body-mass-index and high Alpha-fetoprotein at baseline were possible predictors of a delayed treatment response. ConclusionBulevirtide is a safe treatment option for HDV, leading to a fast hepatological response. Of note, decrease of transaminases precedes virological response. Patients with high viral load and ALT levels respond slower, but non-responders (as classified by Food and Drug administration criteria) still show reduction of viremia. Longer observation periods are required to determine the optimal duration of bulevirtide monotherapy.

ScCURE identifies cell types responding to immunotherapy and enables outcome prediction

A deep understanding of immunotherapy response/resistance mechanisms and a highly reliable therapy response prediction are vital for cancer treatment. Here, we developed scCURE (single-cell RNA sequencing [scRNA-seq] data-based Changed and Unchanged cell Recognition during immunotherapy). Based on Gaussian mixture modeling, Kullback-Leibler (KL) divergence, and mutual nearest-neighbors criteria, scCURE can faithfully discriminate between cells affected or unaffected by immunotherapy intervention. By conducting scCURE analyses in melanoma and breast cancer immunotherapy scRNA-seq data, we found that the baseline profiles of specific CD8+ T and macrophage cells (identified by scCURE) can determine the way in which tumor microenvironment immune cells respond to immunotherapy, e.g., antitumor immunity activation or de-activation; therefore, these cells could be predictive factors for treatment response. In this work, we demonstrated that the immunotherapy-associated cell-cell heterogeneities revealed by scCURE can be utilized to integrate the therapy response mechanism study and prediction model construction.

Postorgasmic illness syndrome: one or several entities? A retrospective cohort study.

Postorgasmic illness syndrome (POIS) is a rare syndrome in which patients experience various physical and cognitive symptoms after ejaculation, and its pathophysiology remains unknown. The aim of this study was to characterize the clinical presentations, disease course, and treatment outcomes in outpatients, as well as to examine the validity of the preliminary criteria and symptom clusters of POIS. This retrospective monocentric study was conducted in a neurourology department, with patients included from 2010 to 2023. The diagnostic criteria and symptom cluster descriptions were based on previous studies. The study focused on the clinical features of POIS, the complementary tests performed, the treatments tried, and their effectiveness. Thirty-seven men were included in the study, with symptom onset occurring at a mean ± SD age of 23.6 ± 7.4years. The mean time from ejaculation to symptom onset was 1hour 22minutes ± 3hours 42minutes. The mean duration of symptoms was 4.7 ± 3.4days. Seventeen patients (46%) developed the symptoms primarily, whereas in 20 (54%) they appeared secondarily. All preliminary criteria were met in 19 patients (51%). The most common symptom clusters were "general" in all 37 patients (100%; eg, asthenia and concentration difficulties) and "head" in 35 patients (95%; mostly headache and a foggy feeling). In terms of treatments, antihistamines and nonsteroidal anti-inflammatory drugs were tried and partially improved symptoms for some patients. This study helps to further characterize POIS by specifying the most frequent symptoms and comparing them with the initial criteria. To our knowledge, this is one of the largest cohorts of patients consulting for symptoms suggestive of POIS. There are limitations due to the retrospective nature of the data collection, such as missing data and imprecision of treatment efficacy. The majority of participants met at least 3 of the preliminary diagnostic criteria, with a majority of symptoms in the general and head clusters. However, the determination of predictive factors for treatment response based on the typology of the disorders remains to be established.

Efficacy of paclitaxel-carboplatin with bevacizumab as a late-line therapy for patients with advanced nonsquamous non-small cell lung cancer: A platinum rechallenge.

There is no well-established late-line treatment for advanced nonsquamous non-small cell lung cancer (NSCLC). Therefore, we retrospectively determined the efficacy and safety of platinum rechallenge with paclitaxel-carboplatin and bevacizumab in patients with nonsquamous NSCLC as a late-line therapy in a clinical setting. Thirty patients with nonsquamous NSCLC who received paclitaxel-carboplatin with bevacizumab therapy as a late-line treatment at Sendai Kousei Hospital (Miyagi, Japan) between December 2011 and December 2021 were enrolled into the study. The efficacy and safety of this treatment were evaluated. The patients were further categorized into responders and nonresponders, and predictive factors of treatment response were estimated. The median progression-free survival (PFS) was 6.3 (range, 4.9-6.8) months, and the median overall survival (OS) was 11.8 (range, 7.2-17.2) months. There were no significant differences in PFS and OS between patients with and those without epidermal growth factor receptor mutations. In the univariate analyses of this study, responders were younger than nonresponders (p = 0.012). No fatal adverse events were reported. With the increase in the number of treatment options in recent years, the sequence of treatments and overall therapeutic strategy are becoming increasingly important. Thus, platinum rechallenge with paclitaxel-carboplatin and bevacizumab, a late-line treatment for patients with nonsquamous NSCLC, may be an effective therapeutic option.

Predictive factors for treatment response and mortality in chronic pulmonary aspergillosis.

Chronic pulmonary aspergillosis (CPA) is associated with significant mortality, and suboptimal antifungal treatment response. We describe predictive factors for treatment response and survival. We retrospectively analysed clinical, serological and radiological parameters at baseline and following antifungal treatment in patients with CPA and correlated with clinical and radiological response and survival. Fifty-nine patients were included with a mean age of 61 years. Thirty (51%) had a diagnosis of COPD. On clinical assessment at 6 months, 21 (36%) had clinically improved, 20 (34%) were clinically stable and 15 (25%) had deteriorated. Radiological improvement was observed in 30 (53%), stability in 11 (19%) and deterioration in 16 (28%). Only a lower C-reactive protein (CRP) at baseline was associated with a favourable clinical-radiological response. On univariate analysis, lower CRP, higher albumin, lower Aspergillus IgG and use of inhaled steroids were associated with lower mortality. An overall favourable response at 6 months was associated with lower mortality. Inflammatory markers and Aspergillus IgG were predictors of mortality in CPA. This suggests that mortality in CPA is driven mainly by the chronic fungal infection itself rather than the underlying disease, therefore early optimised treatment of CPA may lead to improved outcomes.

Treatment outcomes of radium-223 in patients with metastatic castration-resistant prostate cancer: An experience before National Health Insurance reimbursement in Taiwan.

Radium-223 (Ra-223), an α-particle-emitting isotope, inhibits bony metastases and prevents patients from skeletal-related events in metastatic castration-resistant prostate cancer (mCRPC). We retrospectively reviewed the treatment response, predictive factors, and adverse events (AEs) of Ra-223 before the National Health Insurance reimbursement in a Taiwanese tertiary institute. Patients treated with Ra-223 before January 2019 were enrolled and categorized into progressive disease (PD) and clinical benefits (CB) groups. Laboratory data before and after the treatment were collected, and spider plots concerning percentage changes of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and prostate-specific antigen (PSA) were prepared and calculated statistically. CB/PD, baseline ALP, LDH, and PSA levels were also adopted as stratification factors for overall survival (OS). Among 19 patients included, 5 (26.3%) and 14 (73.4%) belonged to the PD and CB groups, respectively, with no significant difference observed in the baseline laboratory data. The percentage changes in ALP, LDH, and PSA levels after Ra-223 treatment were statistically significant among the two groups (ALP: CB 54.3 ± 21.4% vs PD 77.6 ± 11.8%, p = 0.044; LDH: CB 88.2 ± 22.8% vs PD 138.3 ± 49.0%, p = 0.046; PSA: CB 97.8 ± 61.7% vs PD 277.0 ± 101.1%, p = 0.002). The trends of LDH between the two groups in spider plot were separated significantly. There were no differences in the AEs between the two groups. CB had a longer median OS than the PD group (20.50 months vs 9.43 months, p = 0.009). Patients with LDH <250 U/L at baseline tended to have longer OS but without significance. The CB rate of Ra-223 was 73.7%. No predictive factor for treatment response was obtained from pretreatment data. The mean percentage changes in ALP, LDH, and PSA levels compared with baseline significantly differed between the CB and PD groups, especially the LDH levels. The CB and PD groups showed different OS, with LDH levels exhibiting the potential to predict OS.

Identification of Predictive Factors for Pathologic Complete Response in Rectal Cancer Patients Undergoing Neoadjuvant Treatment: A Retrospective Study.

Background: Colorectal cancer is a serious illness, with rectal cancer accounting for thirty percent of all cases. For patients diagnosed with rectal cancer, neoadjuvant downstaging chemoradiotherapy is often necessary due to advanced disease at presentation. However, for certain patients, neoadjuvant chemotherapy can result in a complete response, leading to the possibility of overtreatment during subsequent definitive surgery. Methods: In order to identify predictors for clinical or pathologic complete response, we conducted a retrospective study on 231 patients diagnosed with locally advanced rectal cancer who underwent neoadjuvant treatment. Results: Our results indicate that tumor characteristics remain the primary predictive factors for treatment response in rectal cancer patients. Specifically, we found that a complete pathologic response was more likely in patients with stage I/II disease compared to stage III/IV. However, we did not identify any statistically significant associations between radiotherapy characteristics (such as fractionation, treatment technique or total dose) and complete response rates. Conclusions: In conclusion, our study highlights the importance of tumor stage in predicting pathologic complete response following neoadjuvant chemoradiotherapy for rectal cancer patients. Other clinical and pathologic factors, such as tumor size, may also be important predictors of treatment response and should be explored in future studies.

Peripheral Blood Inflammation Indicators as Predictive Factors for Treatment Response Assessed by MRI in Cervical Cancer Patients Referred for Radiotherapy

Backgroud: Radiotherapy (RT) with or without concurrent chemotherapy is regarded as the standard therapy for locally advanced cervical cancer (International Federation of Gynecology and Obstetrics [FIGO] stage IB2 and above). However, markedly different responses to RT are seen among patients with similar FIGO stages.The study aimed to evaluate the peripheral blood inflammation indicators that may have predictive value for treatment response in cervical cancer patients referred for RT. Methods: This was a retrospective study that enrolled 75 patients who had stages IB2 to IVA cervical cancer, and who underwent RT alone or concurrent chemoradiation therapy (CCRT). All patients were treated at the department of Clinical Oncology of the University of Hong Kong-Shenzhen hospital between November 2015 and April 2020. The endpoint was treatment response assessed by magnetic resonance imaging (MRI) according to the Response EvaluationCriteria in Solid Tumors (RECIST). Multivariate logistic regression models were used to identify predicting values of peripheral blood inflammation indicators, including the systemic immune-inflammation index (SII), neutrophil/lymphocyte ratio (NLR), tumor-related leukocytosis (TRL), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR). Results: The percentage of complete response (CR) was significantly different between different groups of peripheral blood inflammation indicators. The percentage of CR was 64.3%, 57.9%, 81.8% and 48.3% respectively in low SII, NLR, PLR and MLR groups, which was significantly higher than in the high SII group (34.0%), high NLR group (32.4%), high PLR group (30.2%) and high MLR group (35.3%). Multivariate logistic regression revealed that the TRL and PLR were significant prognostic factors for treatment response with an odds ratio of 0.18 (95% confidence interval [95% CI] 0.04–0.77) for TRL and 16.36 (95% CI 3.67–73.04) for PLR. Conclusions: The result revealed that a TRL-negative or lower PLR tumor was associated with radiosensitivity, which may provide important information for the prediction of treatment response in cervical cancer patients referred for RT.

CBT4CBT web-based add-on treatment for cocaine use disorder: Study protocol for a randomized controlled trial.

Cocaine use disorder (CUD) is a chronic condition that presents high relapse rates and treatment dropouts. Web-based interventions have proven to be effective when optimizing face-to-face treatments in different mental health conditions and have the potential to optimize current CUD treatments. However, web-based interventions in addictive behaviors are still limited. The aim of this study is to evaluate whether adding a web-based cognitive behavioral therapy (i.e., CBT4CBT) to standard CUD treatment, improves treatment outcomes in a Spanish sample of patients with severe CUD (which requires inpatient treatment). Additionally, we aim to explore predictive factors of treatment response and treatment gender-related differences. All individuals coming for inpatient cocaine detoxification who meet the inclusion criteria will have the possibility to be part of the study. The participants of this open-label randomized controlled clinical trial (RCT) will be allocated to treatment as usual (TAU) or TAU+CBT4CBT after the hospitalization for cocaine detoxification. During the inpatient treatment they will all receive an individualized psychological intervention. There will be six time point assessments: at 48-72 h of starting inpatient treatment, at the end of inpatient treatment and before starting day care and outpatient treatment, at the end of the 8 weeks CTB4CBT / TAU arm treatment and at three follow-up time points (1-, 3-, and 6-months post-treatment). To the best of our knowledge, this is the first RCT that explores the efficacy of adding a web-based cognitive behavioral therapy to usual CUD treatment with patients of a clinical sample in Europe. IIBSP-CTB-2020-116, NCT05207228. Submitted 8th of April 2021, posted 26 st of January 2022. https://clinicaltrials.gov/ct2/show/NCT05207228?cond=Cocaine+Use+Disorder&draw=2&rank=1.

Evaluation of Low-Molecular-Weight Heparin for Treatment of Portal Vein Thrombosis in Liver Cirrhosis Patients

Background and Objectives: Even though low-molecular-weight heparin (LMWH), including dalteparin, has a critical role in portal vein thrombosis (PVT) treatment in liver cirrhosis (LC) patients, the predictive factors and the proper dose of dalteparin for PVT treatment and relapse have not yet been investigated. Materials and Methods: This retrospective study evaluated the records of LC patients receiving dalteparin from July 2013 to June 2019. The odds ratio (OR) and adjusted OR were calculated from univariate and multivariable analyses, respectively. Results: Among data from 121 patients, the overall recanalization rate of all patients was 66.1% (80 patients). No history of variceal bleeding (OR 4.6, 95% CI: 1.88-11.43) and the case of newly developed thrombus before dalteparin treatment (OR 3.2, 95% CI: 1.24-8.08) were predictive factors associated with increased treatment response. Relapse of PVT occurred in 32 out of 80 patients (40%) who showed a recanalization. The risk of relapse was 3.1-3.9 times higher in those who took more than three months or more than six months from the diagnosis of PVT to dalteparin treatment compared to those who took less than these durations, respectively. In the dosing regimen, patients with the kg-based dosing regimen showed 2.6 times better response than those with the fixed dosing regimen. However, no difference in bleeding complications was observed. Conclusion: In the dosing regimen, the kg-based regimen that was the same as the venous thromboembolism regimen was a better option for the efficacy and safety of dalteparin therapy. Additionally, when treating PVT in LC patients, careful monitoring is recommended for patients with predictive factors for treatment response and relapse of PVT.

Biomarkers and Predictive Factors for Treatment Response to Tumor Necrosis Factor-α Inhibitors in Patients with Psoriasis.

We performed a retrospective and observational study of patients with psoriasis. The aim of this study was to define the laboratory indicators reflecting the treatment response to tumor necrosis factor (TNF)-α inhibitors and the predictors for the treatment response. From January 2010 to June 2022, 28, 15 and 12 patients with psoriasis were treated with infliximab (IFX), adalimumab (ADA) and certolizumab pegol (CZP), respectively. The values of C-reactive protein (CRP), platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio and monocyte to lymphocyte ratio decreased in parallel with psoriasis area and severity index (PASI) at weeks 12 and 52 of treatment. The percentage reduction of the CRP was correlated with that of the PASI at week 52 in all patients and subgroups treated with IFX. The percentage reduction of the PLR was correlated with that of the PASI at week 52 in all patients. Linear multivariate regression analyses revealed that the presence of scalp lesions was associated with a high percentage reduction of the PASI at week 52 in the ADA subgroup. The CRP and PLR might act as biomarkers reflecting the treatment response to TNF-α inhibitors in patients with psoriasis. The presence of scalp lesions might be a predictive factor for a high treatment response to ADA in patients with psoriasis.

Predictive factors of response to infliximab therapy in Brazilian inflammatory bowel disease patients.

Biological therapies have revolutionized the treatment of patients with inflammatory bowel disease (IBD). Infliximab (IFX) has been shown to be effective in inducing and maintaining remission in patients with Crohn's disease and ulcerative colitis. However, about one-third of the patients are primary non-responders, and up to half can lose response over time. Hence, it is important to assess which factors are related to treatment failure. We aimed to identify factors predicting clinical and endoscopic remission with IFX treatment during maintenance therapy in a Brazilian IBD referral center. We conducted a cross-sectional study to describe demographic, clinical, and IBD therapy-related characteristics of IBD patients treated with IFX for at least 6 months in a Brazilian referral center. Subsequently, we evaluated factors associated with clinical and endoscopic remission (primary and secondary outcomes, respectively). We used descriptive statistics to summarize the essential demographic and clinical characteristics of the population. The association of sociodemographic and clinical variables with outcomes was analyzed using multivariable logistic regression. A total of 131 IBD patients (the mean age 41.7 years) were enrolled in this study. Clinical and endoscopic remission were observed in 79.4% and 58.2% of the patients, respectively. In the multivariable analysis, IFX therapy duration and higher albumin levels increased the likelihood of clinical remission, while previous surgery decreased its chance. Prior use of adalimumab and higher C-reactive protein levels reduced the likelihood of endoscopic remission. In summary, this study has enhanced our understanding of the predictive factors of treatment response to IFX in a well-characterized Brazilian IBD population. 4.254.501 and 2.903.748.

Prospective, monocentric, observational study of the long-term effectiveness of omalizumab in chronic urticaria.

Omalizumab, a monoclonal antibody targeting IgE, has been approved in 2014 for the treatment of H1 antihistamine-refractory chronic urticaria. Data on long-term effectiveness and predictive factors for treatment response are currently limited. In this monocentric, prospective, observational study, 112 patients with chronic spontaneous urticaria (CSU) and 32 patients with chronic inducible urticaria (CIndU) were included. In addition to a rapid response, omalizumab also showed good effectiveness on both forms of chronic urticaria over 2 years. Low total IgE and elevated Yersinia IgA were identified as potential predictive markers for slower treatment responses in CSU. In conclusion, the present study highlights the efficacy of omalizumab for the treatment of chronic urticaria. With emerging new therapeutic options for chronic urticaria, further genetic as well as molecular markers are needed to establish patient-specific therapy selection.

Efficacy and Safety of Luspatercept in Adult Patients with Transfusion-Dependent Anemia Due to Very Low, Low and Intermediate Risk Myelodysplastic Syndromes (MDS) with Ring Sideroblasts, Who Had an Unsatisfactory Response to or Are Ineligible for Erythropoietin-Based Therapy: A Retrospective Multicenter Study By Fondazione Italiana Sindromi Mielodisplastiche (FiSiM ETS)

Background: Patients with lower-risk myelodysplastic syndromes (MDS) who develop red blood cells (RBC) transfusion-dependent anemia, experience worse quality of life and shorter survival. Therapeutic strategies after failure of erythropoiesis stimulating agents (ESAs) are limited. Regulatory approval of luspatercept in lower-risk MDS with ring sideroblasts (MDS-RS) offers a novel approach for the treatment of transfusion-dependent anemia in this subset of patients. However, data about luspatercept effectiveness in a real-world clinical setting are lacking. Here we report the results of a multicenter retrospective study including patients who were treated with luspatercept within the Italian compassionate use program. Methods: Eligible patients were ≥ 18 years old, had MDS-RS (2016 WHO classification), met criteria for very low, low, or intermediate IPSS-R risk; were receiving regular RBC transfusions (≥2 units/8 weeks in the 16 weeks before study entry); were refractory to or unlikely to respond to ESAs. Primary end point was transfusion independence (TI) for 8 weeks or longer during weeks 1 through 24; key secondary end point was TI for 12 weeks or longer, assessed during both weeks 1 through 24 and weeks 1 through 48. Other secondary end points included erythroid response (defined by the IWG 2006 criteria), progression to acute myeloid leukemia (AML) and safety analyses. Exploratory analyses were performed to identify predictive factors for treatment response. Results: 184 patients who were enrolled in the Italian luspatercept compassionate use program between December 2020 and December 2021 were analyzed in this study. Median age at enrollment was 74 years (range, 31-88), median time since diagnosis was 43 months, and median time since onset of transfusion-dependence was 23 months. Overall, 123 (66.8%) patients had at least one comorbidity requiring ongoing treatment, 39 (21.2%) had at least three. Baseline median transfusion burden was 6 RBC units every 8 weeks (range, 2-25). At the time of data analysis (June 30, 2022), 130 (73.4%) patients completed at least 24 weeks of treatment. Median time on treatment was 301.5 days, and median follow-up time was 376 days. During the first 24 weeks of the trial, 59 (32%) patients had TI for 8 weeks or longer. The percentage of patients achieving TI increased to 38.6% in the first 48 weeks of the trial. Median duration of TI was 27.9 weeks. Focusing on secondary endpoints, 36 patients (19.6%) had TI for 12 weeks or longer during the first 24 weeks, 52 (28.3%) had TI for 12 weeks or longer considering the first 48 weeks of the trial. A reduction ≥ 4 RBC units/8 weeks during weeks 1-24 was seen in 66 patients (40.2%). Four (2.2%) patients evolved to AML. Serious adverse events were recorded in 27 (15.2%) patients and led to study discontinuation in 5 (2.8%). Overall, treatment was discontinued in 72 (40.7%) patients, mainly for lack of benefit (table 1) The maximum approved dose (1.75 mg/kg) of luspatercept was administered at least once in 144 (81%) patients. Among patients who achieved TI for 8 weeks or longer in the first 48 weeks, luspatercept dose (mg/kg) at response was 1, 1.33 and 1.75 in 31 (46.3%), 18 (29.9%) and 18 (29.9%%) patients, respectively. Logistic regression analysis showed that higher baseline transfusion burden was significantly associated with a lower probability of achieving TI. We identified 3 group of patients stratified according to baseline transfusion burden (group 1, ≤4 units/8 weeks; group 2, 5 to 7 units/8 weeks, group 3, ≥8 units/8 weeks) with a significantly different probability to achieve both the primary endpoint (51.9%, 35.2% and 16.7%, respectively, P<0.01) and the key secondary endpoint (30.8%, 24.1% and 9%, respectively, P<0.01). Patients with higher transfusion burden had higher luspatercept doses at first response (table 2). In patients with low probability to achieve TI (group 2 and 3), a reduction in transfusions equal or greater than 4 units/8 weeks was achieved in 66 (46.2%). Conclusion: Luspatercept was effective for the treatment of transfusion-dependent anemia in MDS-RS in a real-life setting. The benefit extended beyond the achievement of TI and produced a significant reduction in the number of RBC transfusions. Higher baseline transfusion burden was associated with a reduced probability to achieve TI; in these patients, the reduction of transfused RBC units appears a more reliable treatment target. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The role of KRAS and NRAS mutation detection in determining the therapy strategy for colorectal cancer

Colorectal cancer is one of the most frequently diagnosed malignant tumors in men and women, which is a highly heterogeneous group of neoplasms consisting of subclasses with different molecular and clinical characteristics, and, as a consequence, patients with different types of tumors require different treatment protocols. Among the predictive factors of treatment response in patients with metastatic colorectal cancer, the most studied are the genes of the RAS family (KRAS, NRAS). Determination of RAS status is the first step in individual selection of drug therapy in patients with metastatic colorectal cancer. Patients with certain mutations in KRAS and NRAS genes are resistant to anti-EGFR therapy and have a lower median survival than WT (wild type) genotypes, indicating a negative prognosis in the presence of mutations.

Predicting acupuncture efficacy in fibromyalgia: results of a pragmatic open-label study.

To identify the predictive factors of treatment response to acupuncture in patients with fibromyalgia (FM). Patients with FM refractory to standard drug therapy underwent eight weekly acupuncture sessions. Significant improvement, defined as a reduction of at least 30% of the revised Fibromyalgia Impact Questionnaire (FIQR), was assessed at the end of the eight weeks (T1) of treatment and three months after the end of treatment (T2). Univariate analysis was conducted to identify predictors of significant improvement at T1 and T2. Variables that resulted to be significantly associated with clinical improvement at univariate analysis were included in multivariate models. Analyses were conducted on 77 patients (9 males, 11.7%). At T1, significant improvement in FIQR was recorded in 44.2% of patients. At T2, persistent significant improvement was recorded in 20.8% of patients. In the multivariate analysis, predictive variables of treatment failure were tender point count (TPC) (odds ratio [OR] =0.49, 95% confidence interval [95% CI]: 0.28-0.86, p=0.01) and pain magnification (OR=0.68, 95% CI: 0.47-0.99, p=0.04) assessed with the Pain Catastrophising Scale, at T1. At T2, the only predictive variable of treatment failure was concomitant duloxetine use (OR=0.21, 95% CI: 0.05-0.95, p=0.04). High TPC and a tendency for pain magnification predict immediate treatment failure, while duloxetine therapy predicts it three months after completion of the acupuncture course. The identification of clinical characteristics of unfavourable response to acupuncture could help to implement a cost-effective prevention of treatment failure in FM.