Chronic Spontaneous Urticaria: Current and Emerging Biologic Agents.

Antihistamine refractory chronic spontaneous urticaria (CSU) has a prevalence of up to 50%. Anti-immunoglobulin E (IgE) therapies have revolutionized management of CSU, yet refractory cases persist, suggesting a role for biologic agents that impact alternative routes of mast cell stimulation independent of cross-linking at FcεR1. This review addresses anti-IgE and Th2-targeted therapies in the management of CSU. In addition, we explore novel treatments targeting alternative pathways of mast cell activation including MAS-related G protein-coupled receptor-X2 and sialic acid-binding immunoglobulin-like lectin-6, inhibiting intracellular signaling via Bruton's tyrosine kinase, and disrupting KIT activation by SCF.

Factors Associated With Successful Withdrawal of Biologic Agents in Children With Colchicine-Resistant Familial Mediterranean Fever.

BACKGROUND: Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease, and colchicine is the mainstay of treatment. Approximately 5%-10% of patients may respond inadequately to colchicine, and anti-interleukin-1 (anti-IL-1) agents are important treatment options in these patients. The aim of this study was to see whether there is any factor associated with the withdrawal of these anti-IL-1 agents and to investigate the characteristics of colchicine-resistant FMF patients who needed biological therapy. METHODS: Demographic, clinical characteristics, and disease severity of patients, at 2 referral centers, between 2012 and 2022, in whom anti-IL-1 treatment was continued and discontinued, were compared in this study. The international severity scoring system for FMF (ISSF) was used for disease severity assessment. RESULTS: In 64 colchicine-resistant FMF patients, the median (interquartile range) duration of biological treatment was 39 (45) months. Treatment of 26 patients (40.6%) was started with anakinra and 38 (59.4%) with canakinumab. During follow-up, anti-IL-1 treatment was discontinued in 23 patients (35.9%). High ISSF scores before biological treatment, presence of exertional leg pain, subclinical inflammation, and comorbidities were found to be statistically more frequent in the group whose biological therapy could not be discontinued ( p = 0.009, p = 0.006, p = 0.026, p = 0.001, respectively). CONCLUSIONS: Low ISSF scores before biological treatment with no accompanying exertional leg pain, subclinical inflammation, and comorbidities may be stated as an associated factors in terms of the discontinuation of biological agents in colchicine-resistant pediatric FMF patients.

The impact of biologic agents on cardiovascular risk factors in patients with rheumatoid arthritis: A meta analysis.

OBJECTIVE: The purpose of the study is to evaluate the effects of biologic therapy on cardiovascular risk factors in rheumatoid arthritis patients to determine its clinical efficacy. METHODS: Relevant literature was systematically searched in PubMed, Embase, and Cochrane Library databases. Meta-analysis was conducted using standardized mean differences (SMDs) and 95% confidence intervals (CIs) to evaluate cardiovascular risk factors and atherosclerosis. Heterogeneity, sensitivity analysis, and publication bias were assessed. Statistical significance was set at P<0.05. RESULTS: The meta-analysis revealed that biologic treatment in RA patients was associated with decreased high-density lipoprotein cholesterol (HDL-C) levels compared to controls (MD: -0.10, 95% CI: [-0.14, -0.05], P<0.0001). Subgroup analysis based on treatment duration showed heterogeneity and a potential decrease in total cholesterol levels after 12 months of treatment (MD = -0.03, 95% CI [-0.21, -0.15], P = 0.76). Biologic therapy significantly reduced triglyceride levels compared to controls (MD = -0.23, 95% CI [-0.37, -0.09], P = 0.001), as observed in subgroup analysis. Moreover, biologics effectively decreased low-density lipoprotein cholesterol (LDL-C) levels (MD: -0.10, 95% CI: [-0.14, -0.05], P<0.0001). However, biologic treatment was associated with increased inner carotid artery thickness (MD: 0.05, 95% CI: [0.03, 0.07], P<0.0001), indicating potential adverse effects on cardiovascular health. No significant effect on pulse wave velocity (PWV) was observed (MD: -0.23, 95% CI: [-0.80, 0.34], P = 0.43, I2 = 0%, P = 0.55). CONCLUSION: Biologic agents may improve lipid profiles in RA patients but could also have adverse effects on cardiovascular health. Further research is needed to comprehensively understand the impact of biologic therapy on lipid metabolism and cardiovascular outcomes in RA patients. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, CRD42024504911.

The Use of Biologic Agents for the Treatment of Cutaneous Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Review of Reported Cases.

Cutaneous immune-related adverse events encompass a spectrum of dermatological manifestations, including lichenoid reactions, psoriasiform eruptions, eczematous dermatitis, immunobullous disorders, granulomatous reactions, pruritus, vitiligo, and severe cutaneous adverse reactions such as Stevens-Johnson syndrome. The conventional approach to treating high-grade or refractory cutaneous immune-related adverse events has involved high-dose systemic corticosteroids. However, their use is limited owing to the potential disruption of antitumor responses and associated complications. To address this, corticosteroid-sparing targeted immunomodulators have been explored as therapeutic alternatives. Biologic agents, commonly employed for non-cutaneous immune-related adverse events such as colitis, are increasingly recognized for their efficacy in treating various patterns of cutaneous immune-related adverse events, including psoriasiform, immunobullous, and Stevens-Johnson syndrome-like reactions. This review consolidates findings from the English-language literature, highlighting the use of biologic agents in managing diverse cutaneous immune-related adverse event patterns, also encompassing maculopapular, eczematous, and lichenoid eruptions, pruritus, and transient acantholytic dermatosis (Grover disease). Despite the established efficacy of these agents, further research is necessary to explore their long-term effects on antitumor responses.

Impact of DMARD treatment and systemic inflammation on all-cause mortality in patients with rheumatoid arthritis and interstitial lung disease: a cohort study from the German RABBIT register.

OBJECTIVES: To investigate the impact of disease activity and treatment with disease-modifying antirheumatic drugs (DMARDs) on all-cause mortality in patients with rheumatoid arthritis and prevalent interstitial lung disease (RA-ILD). METHODS: Patients with RA-ILD were selected from the biologics register Rheumatoid Arthritis: Observation of Biologic Therapy (RABBIT). Using time-varying Cox regression, the association between clinical measures and mortality was investigated. The impact of DMARDs was analysed by (1) Cox regression considering cumulative exposure (ie, treatment months divided by total months) and (2) time-varying Cox regression as main approach (treatment exposures at monthly level). RESULTS: Out of 15 566 participants, 381 were identified as RA-ILD cases with 1258 person-years of observation and 2.6 years median length of follow-up. Ninety-seven patients (25.5%) died and 34 (35.1%) of these were not receiving DMARD therapy at the time of death. Higher inflammatory biomarkers but not swollen and tender joint count were significantly associated with mortality. Compared with tumour necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs (bDMARDs) exhibited adjusted HRs (aHRs) for mortality below 1, lacking statistical significance. This finding was stable in various sensitivity analyses. Joint aHR for non-TNFi biologics and JAKi versus TNFi was 0.56 (95% CI 0.33 to 0.97). Receiving no DMARD treatment was associated with a twofold higher mortality risk compared with receiving any DMARD treatment, aHR 2.03 (95% CI 1.23 to 3.35). CONCLUSIONS: Inflammatory biomarkers and absence of DMARD treatment were associated with increased risk of mortality in patients with RA-ILD. Non-TNFi bDMARDs may confer enhanced therapeutic benefits in patients with RA-ILD.

Assessing the steroid-sparing effect of biological agents in randomized controlled trials for lupus: a scoping review.

Prompt disease control of flares in patients with systemic lupus erythematosus (SLE) is a priority in treatment strategy planning. However, the long-term dosage-related collateral effects of glucocorticoids (GCs) have pushed researchers towards the identification and utilization of novel biological agents that could both induce and maintain low disease activity and remission, especially in the context of lupus nephritis (LN). This scoping review aims at assessing the current evidence of the potential steroid-sparing effect of biologic therapies by reviewing phase II and phase III randomized, placebo-controlled trials involving SLE/LN patients. A scoping review of the literature was carried out in accordance with PRISMA-ScR recommendations. Risk of bias was assessed through the utilization of the Cochrane Collaboration's tool for randomized controlled trials (RCTs). Eight RCTs met the inclusion criteria and were included in this analysis (treatment drug, 7 belimumab; 1 anifrolumab). Four studies showed a definite steroid-sparing effect (treatment drug, 3 belimumab; 1 anifrolumab), while in the remaining four RCTs, the steroid-sparing effect was not observed. When focusing on phase III trials, the overall quality of the studies resulted fair or good considering the risk of bias. However, a degree of heterogeneity of steroid regimen protocol (considering initial dosage, tapering and rescue treatment allowance) was observed. While a growing body of evidence is supporting the safety and efficacy of biological treatment in SLE, the evidence on their steroid-sparing effect remains scattered. Future research needs to pursue the identification of precise SLE clusters of patients who would benefit most from a specific treatment protocol with a definite steroid-sparing effect.

Comparative maintenance performance of all biologic agents and small molecules in ulcerative colitis: a network meta-analysis.

BACKGROUND AND AIMS: Βiologic agents and small molecules have expanded the therapeutic armamentarium of moderate to severe ulcerative colitis (UC). However, their comparative efficacy and safety performance as maintenance treatments have not been sufficiently explored. We performed a systematic review and network meta-analysis (NWM) to assess the comparative efficacy and safety of all approved and emerging treatments for maintenance in moderate to severe UC. METHODS: We searched Pubmed/Medline, EMBASE, and Cochrane Library databases for relevant RCTs through April 2023. The primary endpoint was clinical remission at the end of the maintenance therapy. Data were analyzed by means of a Bayesian NWM. The ranking probability concerning efficacy and safety was evaluated by means of surfaces under cumulative ranking (SUCRA) values. RESULTS: There were 20 eligible RCTs with 7660 patients randomized to 20 treatments. RCTs were grouped into two study designs, that is, re-randomization of patients after an induction period and treat-through patients. Concerning efficacy, in re-randomized patients, upadacitinib 30 mg/day was ranked first (SUCRA 94.9%) whereas in treat-through patients etrasimod 2 mg/day was ranked first (SUCRA 91.1%). The integrated efficacy-safety hierarchical analysis, showed that tofacitinib 10 mg had the best efficacy-safety therapeutic profile in re-randomized patients, whereas in treat-through patients infliximab 3.5 mg/Kg Q8W showed the best efficacy-safety profile. CONCLUSION: For maintenance treatment, in moderate to severe UC, this NWM showed that upadacitinib 30 mg/day and etrasimod 2 mg/day were ranked best for efficacy in re-randomized and treat-through patients respectively. Tofacitinib 10 mg/day and infliximab 3.5 mg/Kg Q8W showed the best efficacy-safety therapeutic profile in re-randomized and treat-through patients respectively.

Real-life management of psoriasis with biological agents during pregnancy.

BACKGROUND: French guidelines recommend stopping biologic treatment of psoriasis between 3 and 24 weeks before conception in accordance with the relevant Summary of Product Characteristics (SmPC). The aim of this study was to evaluate the real-life practice of dermatologists in the management of pregnant women with psoriasis previously treated with biologic agents. We wished to assess the level of practitioner adherence to the relevant SmPCs. MATERIAL AND METHODS: We conducted a study in collaboration with GRPso and Resopso. A computerized questionnaire was completed by the practitioners. We performed descriptive statistics and studied the profile of the practitioners, their level of confidence with continuation of biological agents during pregnancy, and their reported practices on the use of biological agents in pregnancy. Statistical analyses were performed using XLSTAT. A p-value of less than 0.05 was considered significant. RESULTS: A total of 63 dermatologists (women: 71%; mean age 43.8 years) participated in this study, the majority of whom were hospital-based (87%). Recommendations were followed by 36.5% of practitioners, while 44% reported discontinuing biologic agents on diagnosis of pregnancy, and 20.5% reported using these agents during pregnancy. Among dermatologists with more than ten years of experience, 19% reported following the SmPC. Among dermatologists with a patient base >200 (patients treated with biologic agents for psoriasis), 19% reported following the SmPC compared to 54% of practitioners with less than 50 patients. The mean age of dermatologists following the SmPC was 41 years vs. 47 years for those not following the SmPC. DISCUSSION: The majority of practitioners do not follow recommendations on discontinuation of biologic agents before the planning of pregnancy by patients.

Comparison of the outcomes of Pneumocystis jirovecii pneumonia in rheumatoid arthritis patients treated with and without biologics.

BACKGROUND: To investigate the outcomes of Pneumocystis jirovecii pneumonia (PCP) between patients with rheumatoid arthritis (RA) treated with and without biologics before PCP onset. PATIENTS AND METHODS: We retrospectively included rheumatoid arthritis (RA) patients with PCP treated with and without biologics before PCP onset. The primary endpoints were 30-day and 180-day survival rates, and the secondary endpoint was severe PCP, including in-hospital death, intensive care unit admission, and requirement of respiratory support during hospitalization. RESULTS: Eighty-two patients were enrolled in this study, including the Biologics group (n = 39) and Non-Biologics group (n = 43). There were no significantly differences in the 30-day and 180-day survival rates and severe PCP rate in the Biologics group and the Non-Biologics group before and after adjusting the patient characteristics. Kaplan-Meier survival curves for death showed no significantly differences between the Biologics and Non-Biologics groups. Cox regression hazard analysis revealed that the average daily prednisolone dose within 90 days before PCP onset was weakly associated with mortality after PCP. CONCLUSIONS: Biologic use before PCP onset did not increase the severity and mortality of PCP compared to non-biologics use in patients with RA.

Comparative effectiveness of biologics in patients with rheumatoid arthritis stratified by body mass index: a cohort study in a Swiss registry.

OBJECTIVES: Obesity is associated with lower treatment response in patients with rheumatoid arthritis (RA). In patients with obesity, abatacept was suggested as a preferable option to tumour necrosis factor-alpha inhibitors. We aimed to assess the comparative effectiveness of etanercept, infliximab and abatacept, compared with adalimumab, in patients with RA with obesity. Secondarily, we also investigated this in patients with overweight and normal weight for completeness. DESIGN: Observational cohort study. SETTING: Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry (1997-2019). PARTICIPANTS: Adult patients with RA from the SCQM registry who received etanercept, infliximab, abatacept or adalimumab as their first biological or targeted synthetic disease-modifying antirheumatic drug were classified based on their body mass index (BMI) at the start of that treatment in three cohorts: obese, overweight, normal weight. They were followed for a maximum of 1 year. EXPOSURE: The study exposure of interest was the patients' first biological, particularly: etanercept, infliximab and abatacept, compared with adalimumab. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary study outcome was remission within 12 months, defined as 28-joint Disease Activity Score (DAS28) <2.6. Missingness was addressed using confounder-adjusted response rate with attrition correction. Logistic regression was used to compare the effectiveness of etanercept, infliximab and abatacept versus adalimumab. Each BMI cohort was addressed and analysed separately. RESULTS: The study included 443 obese, 829 overweight and 1243 normal weight patients with RA. There were no statistically significant differences in the odds of DAS28-remission at ≤12 months for etanercept, infliximab and abatacept, compared with adalimumab, in any of the BMI cohorts. CONCLUSIONS: No differences in DAS28-remission were found between the study drugs and adalimumab as first biologic in patients with RA, independently of the BMI cohort. We did not find evidence that treatment with abatacept increased the likelihood of remission compared with adalimumab among obese patients with RA.

Burden of non-serious infections during biological use for rheumatoid arthritis.

INTRODUCTION: Biologicals have become a cornerstone in rheumatoid arthritis (RA) treatment. The increased risk of serious infections associated with their use is well-established. Non-serious infections, however, occur more frequently and are associated with a high socioeconomic burden and impact on quality of life but have not received the same attention in the literature to date. The aim of this study was to gain insight into the various non-serious infections reported in RA patients using biologicals and their experienced burden. MATERIALS AND METHODS: The Dutch Biologic Monitor was a prospective observational study that included adults with rheumatoid arthritis and biological use who answered bimonthly questionnaires on the adverse drug reactions (ADRs) they experienced from their biological and reported the associated impact score (ranging from 1, no impact, to 5, very high impact). ADRs were assigned a MedDRA code by pharmacovigilance experts and labeled as definite, probable, possible or no infection by infectious disease professionals. Descriptive statistics were performed using medians and interquartile ranges. RESULTS: A total of 586 patients were included in the final analysis. Eighty-five patients (14.5%) reported a total of 421 ADRs labeled as probable or definite infections by the experts. Patient-assigned burden was ADR-specific. Upper respiratory tract infections were most frequently reported and had a high rate of recurrence or persistence, with a median impact score of 3.0 (IQR 2.0-3.0) which remained stable over time. DISCUSSION: Non-serious infections significantly outnumbered serious infections in this real-life cohort of RA patients using biologicals (77.1 non-serious infections and 1.3 serious infections per 100 patient years, respectively). Infections in the upper respiratory tract were rated as having an average burden, which remained constant over a long period of time. Awareness of the impact of recurrent and chronic non-serious infections may enable healthcare professionals to timely treat and maybe even prevent them, which would lessen the associated personal and socioeconomic burden.

Machine learning using clinical data at baseline predicts the medium-term efficacy of ustekinumab in patients with ulcerative colitis.

Predicting the therapeutic response to biologics before administration is a key clinical challenge in ulcerative colitis (UC). We previously reported a model for predicting the efficacy of vedolizumab (VDZ) for UC using a machine-learning approach. Ustekinumab (UST) is now available for treating UC, but no model for predicting its efficacy has been developed. When applied to patients with UC treated with UST, our VDZ prediction model showed positive predictive value (PPV) of 56.3% and negative predictive value (NPV) of 62.5%. Given this limited predictive ability, we aimed to develop a UST-specific prediction model with clinical features at baseline including background factors, clinical and endoscopic activity, and blood test results, as we did for the VDZ prediction model. The top 10 features (Alb, monocytes, height, MCV, TP, Lichtiger index, white blood cell count, MCHC, partial Mayo score, and CRP) associated with steroid-free clinical remission at 6 months after starting UST were selected using random forest. The predictive ability of a model using these predictors was evaluated by fivefold cross-validation. Validation of the prediction model with an external cohort showed PPV of 68.8% and NPV of 71.4%. Our study suggested the importance of establishing a drug-specific prediction model.

Efficacy of biological agents combined with oral immunotherapy (OIT) for food allergy: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Food allergy affects a large population throughout the world. Recently, oral immunotherapy (OIT) has been reported as an effective treatment for severe food allergy. Although OIT was successful in numerous trials in desensitisation, adverse events including anaphylaxis during OIT frequently occur. Additionally, some patients fail to be desensitised after OIT and the response to treatment is often not sustained. As a further adjunctive therapy to facilitate OIT, the role of biological agents has been identified. For example, efficacy and safety of omalizumab as an adjuvant therapy of OIT has become apparent through some RCTs and observational studies. Interest towards this topic is growing worldwide, and ongoing trials will provide additional data on the biologics in food allergy.We aim to systematically analyse the efficacy and safety of OIT combined with biological agents for food allergy. METHODS AND ANALYSIS: This paper provides a protocol for a systematic review of the relevant published analytical studies using an aggregate approach following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. Two authors will perform a comprehensive search for studies on MEDLINE/PubMed, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. Subsequently, two independent authors will perform abstract screening, full-text screening and data extraction. A meta-analysis will be conducted as appropriate. ETHICS AND DISSEMINATION: The protocol of this systematic review will be provided in a peer-reviewed journal. As the researchers will not identify the individual patients included in the studies, they do not need to acquire ethics approval. PROSPERO REGISTRATION NUMBER: CRD42022373015.

Use of Efficiency Frontiers to Align Prices and Clinical Benefits of Biologic Therapies for Plaque Psoriasis.

Importance: The US lacks a systematic approach for aligning drug prices with clinical benefit, and traditional cost-effectiveness analysis (CEA) faces political obstacles. The efficiency frontier (EF) method offers policymakers an alternative approach. Objective: To assess how the EF approach could align prices and clinical benefits of biologic medications for plaque psoriasis and estimate price reductions in the US vs 4 peer countries: Australia, Canada, France, and Germany. Design and Setting: This health economic evaluation used the EF approach to compare the prices and clinical benefits of 11 biologics and 2 biosimilars for plaque psoriasis in the US, Australia, Canada, France, and Germany. Data were collected from February to March 2023 and analyzed from March to June 2023. Main Outcome Measures: EFs were constructed based on each biologic's efficacy, measured using the Psoriasis Area and Severity Index (PASI) 90 response rate, and annual treatment cost as of January 2023; US costs were net of estimated manufacturer rebates. Prices based on the EF were compared with traditional CEA-based prices calculated by the Institute for Clinical and Economic Review at a threshold of $150 000 per quality-adjusted life-year gained. Results: Among 13 biologics, PASI 90 response rates ranged from 17.9% (etanercept) to 71.6% (risankizumab); US net annual treatment costs ranged from $1664 (infliximab-dyyb) to $79 277 (risankizumab). The median (IQR) net annual treatment cost was higher in the US ($34 965 [$20 493-$48 942]) than prerebate costs in Australia ($9179 [$6691-$12 688]), Canada ($15 556 [$13 017-$16 112]), France ($9478 [$6637-$11 678]), and Germany ($13 829 [$13 231-$15 837]). The US EF included infliximab-dyyb (PASI 90: 57.4%; annual cost: $1664), ixekizumab (PASI 90: 70.8%; annual cost: $33 004), and risankizumab (PASI 90: 71.6%; annual cost: $79 277). US prices for psoriasis biologics would need to be reduced by a median (IQR) of 71% (31%-95%) to align with those estimated using the EF; the same approach would yield smaller price reductions in Canada (41% [6%-57%]), Australia (36% [0%-65%]), France (19% [0%-67%]), and Germany (11% [8%-26%]). Except for risankizumab, the EF-based prices were lower than the prices based on traditional CEA. Conclusions and Relevance: This economic evaluation showed that for plaque psoriasis biologics, using an EF approach to negotiate prices could lead to substantial price reductions and better align prices with clinical benefits. US policymakers might consider using EFs to achieve prices commensurate with comparative clinical benefits, particularly for drug classes with multiple therapeutic alternatives for which differences can be adequately summarized by a single outcome measurement.

The New Therapeutic Frontiers in the Treatment of Eosinophilic Esophagitis: Biological Drugs.

Eosinophilic esophagitis (EoE) is a multifaceted disease characterized by a wide heterogeneity of clinical manifestations, endoscopic and histopathologic patterns, and responsiveness to therapy. From the perspective of an effective approach to the patient, the different inflammatory mechanisms involved in the pathogenesis of EoE and biologics, in particular monoclonal antibodies (mAbs), targeting these pathways are needed. Currently, the most relevant is dupilumab, which interferes with both interleukin (IL)-4 and IL-13 pathways by binding IL-4 receptor α, and is the only mAb approved by the European Medicine Agency and US Food and Drug Administration for the treatment of EoE. Other mAbs investigated include mepolizumab, reslizumab, and benralizumab (interfering with IL-5 axis), cendakimab and dectrekumab (anti-IL-13s), tezepelumab (anti-TSLP), lirentelimab (anti-SIGLEG-8), and many others. Despite the undeniable economic impact of biologic therapies, in the near future, there will be room for further reflection about the opportunity to prescribe biologic agents, not only as a last-line therapy in selected cases such as patients with comorbidities involving common pathways. Although recent findings are very encouraging, the road to permanent success in the treatment of EoE is still long, and further studies are needed to determine the long-term effects of mAbs and to discover new potential targets.

Risk factor of non-tuberculous Mycobacterium infection in patients with rheumatoid arthritis and other autoimmune diseases receiving biologic agents: A multicenter retrospective study.

BACKGROUND: Evidence regarding the association of the usage of biologic agents (Etanercept, Tocilizumab, adalimumab and so on), such as anti-tumor necrosis factor α, with the incidence and risk factors of non-tuberculous Mycobacteria (NTM) infection is limited. Therefore, this study aimed to investigate the incidence and risk factors of NTM and their associations with biologic agents' usage, and also investigated the potential of Mycobacterium avium complex (MAC) antibodies as a predictor of NTM infection development. METHODS: This retrospective study included 672 patients with autoimmune diseases from four hospitals in Nagasaki, Japan, from January 1, 2011, to June 30, 2019, who fulfilled the inclusion criteria. RESULTS: Of the 672 patients, 9 (1.3%) developed complicated NTM infection, including two with disseminated infection, after the introduction of biologic agents. Of the nine patients, two died due to NTM infection but none tested positive for MAC antibodies prior to initiation of biologic agents. The mortality rate was higher in patients complicated with NTM than without NTM (22.2% vs 2.6%, P = 0.024). The corticosteroids dosage at the time of initiating the biologic agents was significantly higher in the NTM group than in the non-NTM group (median, 17 mg vs 3 mg, P = 0.0038). CONCLUSION: In the patients undergoing therapy with biologic agents, although NTM complication was rare, it could be fatal. In particular, for patients on a relatively high dose corticosteroids, careful observation is essential for identifying NTM complication, even if the MAC antibody test is negative.

Latent and active tuberculosis development in patients with rheumatoid arthritis receiving biologic disease-modifying antirheumatic drugs: A single-center prospective study.

Biologics have revolutionized the treatment of rheumatoid arthritis (RA) in recent years. However, data from clinical trials and actual clinical practice have shown that biologics currently in use may constitute a risk factor for reactivation of tuberculosis (TB) in patients with latent TB infection. Therefore, screening for latent and active TB infection is mandatory before initiating biologic therapy in patients with RA. This prospective study aimed to analyze the clinical characteristics of patients with RA receiving biologic disease-modifying antirheumatic drugs at Bach Mai Hospital, Vietnam, between 2017 and 2022, and to identify factors affecting the occurrence of active and latent TB infection among these patients. Over a 12-month follow-up period, latent TB infection was confirmed in 20% of the total 180 included patients, while 3 (1.7%) patients developed active TB (one case of pulmonary, pleural, and gluteal TB each). History of TB risk factor exposure and lack of education were significantly associated with the occurrence of active and latent TB infection, with odds ratios (95% confidence intervals [CIs]) of 1.98 (1.78; 2.2) and 1.45 (1.31; 1.6), respectively. Follow-up duration and number of X-ray, computed tomography, bronchoscopy, and sputum acid-fast bacteria examinations were identified as factors that can aid in the early diagnosis of latent TB, with odds ratios (95% CIs) of 1.00 (1; 1.01), 1.02 (1; 1.05), 1.12 (1.11; 1.2), 1.11 (1.09; 1.2), and 1.13 (1.09; 1.17), respectively. Our study showed that, in countries with high TB burden like Vietnam, latent TB infection has high prevalence among patients with RA. We also provide useful information for the screening, monitoring, and treatment of latent and active TB infection in patients with RA.

Decoding treatment efficacy: uncovering response and failure dynamics to biologics in asthma.

INTRODUCTION: Asthma is a global health problem, with alarming prevalence and mortality rates. Biologic therapies, particularly monoclonal antibodies such as omalizumab, have emerged as promising alternatives, targeting specific immune pathways. This article assesses the efficacy of these biologics in asthma management and attempts to reveal factors associated with their response and failure dynamics. AREA COVERED: This article explores the efficacy of biologics in asthma, biomarkers, and the relationship between asthma phenotypes (including eosinophilic and non-eosinophilic (neutrophilic) types) and biologic treatments; particularly their effectiveness for each subtype. EXPERT OPINION: Personalized asthma management that incorporates molecular insights as well as individual variations is of outmost necessity. An emphasis is put on immunological profiling, understanding comorbidities and considering individual patient factors when managing asthma. Cutting-edge phenotyping tools including omic technologies play a crucial role in improving asthma management precision. Variability in patient responses to biologic treatments such as non-responders, partial responders and super responders poses a formidable challenge to effective asthma care management strategies.