Biologics Research Articles

Curing Psoriasis.

As medicine advances, cures are being found for diseases that were previously considered incurable, as is the case for some types of cancer. Traditionally, the term cure is reserved for resolution of disease, both at a clinical and a molecular level, which continues after cessation of treatment. Biologic therapies have revolutionized the definition of remission in severe psoriasis, with some patients achieving long-lasting disease suppression, but the disease nearly always relapses on withdrawal of the drug. Our improved understanding of the pathomechanisms of psoriasis, coupled with anecdotal reports of long-term clearance of the disease after cell-based therapies, leads us to the hypothesis that psoriasis is curable. We propose that cure of psoriasis can be achieved by restoring immune homeostasis through a combinatorial, personalized medicine approach encompassing early intervention to include biologics, advanced therapeutics, and lifestyle modification.

PreMLS: The undersampling technique based on ClusterCentroids to predict multiple lysine sites.

The translated protein undergoes a specific modification process, which involves the formation of covalent bonds on lysine residues and the attachment of small chemical moieties. The protein's fundamental physicochemical properties undergo a significant alteration. The change significantly alters the proteins' 3D structure and activity, enabling them to modulate key physiological processes. The modulation encompasses inhibiting cancer cell growth, delaying ovarian aging, regulating metabolic diseases, and ameliorating depression. Consequently, the identification and comprehension of post-translational lysine modifications hold substantial value in the realms of biological research and drug development. Post-translational modifications (PTMs) at lysine (K) sites are among the most common protein modifications. However, research on K-PTMs has been largely centered on identifying individual modification types, with a relative scarcity of balanced data analysis techniques. In this study, a classification system is developed for the prediction of concurrent multiple modifications at a single lysine residue. Initially, a well-established multi-label position-specific triad amino acid propensity algorithm is utilized for feature encoding. Subsequently, PreMLS: a novel ClusterCentroids undersampling algorithm based on MiniBatchKmeans was introduced to eliminate redundant or similar major class samples, thereby mitigating the issue of class imbalance. A convolutional neural network architecture was specifically constructed for the analysis of biological sequences to predict multiple lysine modification sites. The model, evaluated through five-fold cross-validation and independent testing, was found to significantly outperform existing models such as iMul-kSite and predML-Site. The results presented here aid in prioritizing potential lysine modification sites, facilitating subsequent biological assays and advancing pharmaceutical research. To enhance accessibility, an open-access predictive script has been crafted for the multi-label predictive model developed in this study.

Transforming Care in SEA: Evidence and Considerations for Evolution of the Current Treatment Paradigm

This article reviews an industry symposium held on 8 September 2024 as part of the European Respiratory Society (ERS) Congress 2024 in Vienna, Austria, which brought together four experts to discuss the current treatment paradigm for severe eosinophilic asthma (SEA), including the role of biologics and background medication tapering. Katrin Milger-Kneidinger, Professor of Respiratory Medicine at the University Hospital of the Ludwig Maximilian University Munich (LMU), in Germany, and the MedUni Graz, in Austria, explored the critical role eosinophils play in SEA pathology and how biologic therapies targeting eosinophils can address key disease features, including airway remodelling, airway hyperresponsiveness (AHR), and mucus production. Felix Herth, Professor of Pulmonary and Critical Care Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, discussed persistent airflow obstruction (PAO) in patients with SEA, focusing on a typical patient profile to understand the clinical manifestation and opportunities for management. Stephanie Korn, Professor of Pulmonary and Respiratory Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, and Head of the Clinical Research Centre, Institute für Klinische Forschung (IKP) Pneumologie in Mainz, Germany, presented on remission as a clinical target in SEA, focusing on how biologics can help achieve remission in some patients. Lastly, in a discussion led by symposium chair Stefano Del Giacco, Professor of Medicine, Allergy, and Clinical Immunology, at the University of Cagliari, Sardinia, in Italy, the experts agreed that a positive practice change would be to get more patients with relevant clinical manifestations on biologics, and that background medication tapering, when appropriate, could lead to improved patient outcomes and quality of life (QoL) in SEA.

Abstract Highlights

The following abstract highlights spotlight selected abstracts presented at the European Respiratory Society (ERS) Congress 2024. They cover key topics, including lung cancer screening and management, Chronic obstructive pulmonary disease, cystic fibrosis, effects of smoking on airway inflammation, and the role of biologic therapy in asthma. These highlights showcase the latest cutting-edge developments and most talked-about topics in the field today.

Infliximab versus interferon-alpha in the treatment of Behçet's Syndrome: Clinical data from the BIO-BEHÇET'S randomised controlled trial.

Whilst biologic therapy is used for Behçet's Syndrome of all subtypes refractory to first-line immunomodulation, there has been an absence of high-quality evidence-and no predictive biomarkers to optimally inform choice. BIO-BEHÇET'S was a randomised, controlled, head-to-head clinical trial comparing the two most frequently used biologics in active refractory Behçet's. Bayesian-designed, pragmatic, standard of care, two-arm, parallel head-to-head trial at four UK centres. Patients with active disease randomised to infliximab or interferon-α2a, and received follow-up with symptom-directed examination at Weeks 12 and 24. Primary outcome was Behçet's Disease Activity Index (BDAI) at 12 weeks. Secondary outcomes included BDAI at 24 weeks and significant improvement in individual organ systems, including ocular symptoms, oral and genital ulcers, arthritis pain, quality of life, disease activity, and steroid use. Biomarkers were also investigated but are reported elsewhere. 79 patients were recruited. Both treatments were equally effective, with a mean difference of 0.13 in BDAI (80% CI: -0.19, 0.46). No significant differences were observed for secondary outcomes, though there were clinically significant within-group reductions for each over time. A modest steroid-sparing effect was observed, with complete cessation of steroids in 20% and 44% of those randomised to infliximab and interferon-α2a, respectively. There was a trend for minor benefit in favour of infliximab in terms of tolerability and persistence. In this first reported, high-quality, head-to-head trial of two biologics in Behçet's, both infliximab and interferon-α2a showed comparable short-term clinical efficacy and safety in refractory active disease of all subtypes. EudraCT: 2014-005390-36; ISRCTN: ISRCTN49793874.

Celecoxib in rheumatic diseases: possibilities and prospects. Brief descriptive survey

Chronic pain is the main manifestation of rheumatic diseases (RD), it determines the main complaints and worsens the quality of life of patients. The problem of effective control of chronic pain in rheumatology remains a current issue despite the successes in the development of new drugs for pathogenetic therapy, especially in immunoinflammatory RD. For example, 40-50% of patients with rheumatoid arthritis (RA), even those receiving biologic disease-modifying antirheumatic drugs and Janus kinase inhibitors, require analgesics. According to several population studies, about 50% of patients with the most common RD, osteoarthritis (OA) are forced to take various analgesics on a regular basis.The most popular class of analgesics with proven efficacy in RA, spondyloarthritis (SpA) and OA are non-steroidal anti-inflammatory drugs (NSAIDs). As has been shown in several meta-analyses, NSAIDs are superior to placebo and paracetamol in their therapeutic effect, are not inferior to opioids and are better tolerated overall. However, the use of NSAIDs can be associated with the development of dangerous adverse events (AEs), which requires careful monitoring of the patient's condition, considering comorbid diseases and risk factors. It is very important to choose a drug with a balanced ratio of efficacy and low risk of gastrointestinal and cardiovascular AEs. One such drug is celecoxib, whose therapeutic potential and relative safety have been confirmed in RA, SpA and OA. A differentiated approach to celecoxib prescription makes it possible to achieve a maximum therapeutic result with a minimum risk of AEs. For severe pain, treatment starts with a dose of 400 mg/day, followed by a switch to a maintenance dose of 200 mg/day.

Prognostic model for gastric cancer patients with COVID-19 and network pharmacology study on treatment by lentinan

Patients with gastric cancer (GC) are more susceptible to coronavirus disease 2019 (COVID-19), which further worsens their already challenging prognosis. However, there are no effective treatment options for these patients. Lentinan is a potent bioactive component with antiviral and antitumor effects. We hypothesized that lentinan might exert powerful pharmacological effects in patients with GC and COVID-19. In this study, a prognostic model of patients with GC/COVID-19 was constructed and used to apply a network pharmacology approach to reveal biological functions, drug targets, and molecular mechanisms of the action of lentinan against GC/COVID-19. Clinical analysis revealed key prognostic genes in patients with GC/COVID-19. The results of network pharmacology analysis suggested that the therapeutic effect of lentinan on GC/COVID-19 mainly involves the modulation of several neutrophil-related biological processes, as well as the nucleotide-binding and oligomerization domain-like receptor and interleukin-17 signaling pathways. In addition, C-X-C motif chemokine ligand 8, vascular endothelial growth factor A, ribonuclease 3, and F2 were identified as key genes of lentinan against GC/COVID-19. Key prognostic genes were identified in patients with GC/COVID-19 through the construction of a prognostic model. Pharmacological functions and signaling pathways of lentinan against GC/COVID-19 were revealed. These included the regulation of neutrophils and NOD-like receptor signaling pathways. The findings provide the first published evidence of the potential value of lentinan as a complementary therapy for GC/COVID-19.

Steroid-sparing strategy for the treatment of vasculitis associated with antineutrophil cytoplasmic antibodies

Glucocorticoids (GC) and immunosuppressants (IS) are traditional treatments for vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), often resulting in the development of infections, diabetes mellitus and other adverse events (AEs). The development of a steroid-sparing strategy using biologic disease-modifying antirheumatic drugs (bDMARDs, including rituximab, etc.) and synthetic targeted drugs (avacopan) has radically improved the course of the disease. Currently, there are increasing number of basic and clinical trials of numerous bDMARDs that effectively reduce the number of AEs associated with GC and IS. The steroid-sparing therapeutic strategy not only shows considerable efficacy, but also opens up new perspectives for the treatment of patients with ANCA-associated systemic vasculitis.

"Atherosclerotic" phenotype of rheumatoid arthritis. What do we know about it?

Several studies have shown that systemic rheumatoid inflammation may cause induction and accelerated progression of atherosclerotic vascular lesions, which in turn may lead to more frequent development of cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA) compared to the general population.Objective. To evaluate the presence, nature and role of conventional and RA-specific risk factors for the development of CVD in patients with active RA in real-life clinical practice.Material and methods. Data from 967 patients with confirmed active RA were analyzed. Biologic disease-modifying antirheumatic drugs (DMARDs) or targeted DMARDs were prescribed/switched due to the ineffectiveness of previous therapy. Patients were divided into two groups: with and without CVD. In addition, comparable age subgroups of elderly (60–74 years) and middle-aged (45–59 years) patients were formed in each group. In all patients, clinical and laboratory parameters of RA activity, presence of extra-articular manifestations, the severity and progression of RA and characteristics of pharmacotherapy were analyzed. In addition, concomitant diseases and several traditional risk factors for the development of CVD were analyzed in all RA patients.Results and discussion. In patients with similar RA activity and duration, there is a parallel, tatistically significant accumulation of traditional CVD risk factors with increasing age-related CVD. The incidence of arterial hypertension, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, thyroid pathology, anemic syndrome, dyslipidemia, hyperuricemia and obesity was significantly higher in the group of elderly RA patients with CVD than in the group of middle-aged patients.Conclusion. It seems appropriate to identify a specific variant of RA that is closely associated with atherosclerosis.

Pharmacoeconomic analysis of rituximab and belimumab therapy in patients with systemic lupus erythematosus

The progressive course of systemic lupus erythematosus (SLE) with high activity and severe internal organs involvement requires the prescription of expensive biologic disease-modifying antirheumatic drugs (bDMARDs), rituximab (RTM) and belimumab (BLM), whose comparative clinical and economic efficacy has not been adequately studied.Objective: to evaluate the clinical and economic efficacy of RTM and BLM therapy in patients with SLE.Material and methods. The study included 50 SLE patients who were divided into two groups and received RTM (group 1, n=25) or BLM (group 2, n=25) therapy for 12 months. The clinical and economic analysis was performed with the cost-effectiveness method using the cost-per-responder (CPR) model. A clinically significant improvement in SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index modified 2K; Δ ≥4) was considered a response to therapy. Direct and indirect costs were considered in the analysis.Results and discussion. Against a background of therapy, there was a decrease in SLE activity with a decrease in median SLEDAI-2K in group 1 from 12 [10.5; 18] to 8 [4; 10] and in group 2 from 10 [8; 14.5] to 4 [2; 4] (p< 0.001 in both cases). A clinically significant improvement was observed in 56% of patients in group 1 and 72% of patients in group 2. The peculiarities of the BLM dosing regimen caused higher (1.7 times) total costs than in the case of RTM. According to the CPR value, RTM showed a greater benefit (1.3 times) than BLM (954 thousand rubles versus 1.25 million rubles). The incremental cost-effectiveness ratio (ICER) was 1.4 million rubles, which does not exceed the threshold of willingness to pay for a domestic patient.Conclusion. When comparing BLM and RTM therapy for SLE patients in real-life clinical practice, greater clinical and economic efficiency was demonstrated for RTM. BLM therapy was found to be “cost-effective”.

Juvenile Dermatomyositis: Updates in Pathogenesis and Biomarkers, Current Treatment, and Emerging Targeted Therapies.

Juvenile dermatomyositis is a rare systemic inflammatory autoimmune disease involving muscle, skin, and vessels. Most patients do not fully respond to initial therapy, instead having a chronic refractory or polycyclic disease course. Pathogenesis is not completely understood, but immune cell dysregulation, particularly of B cells, mitochondrial dysfunction, changes in neutrophils and neutrophil extracellular traps (NETs), and increased type I and type II interferon (IFN) signaling have been described. There are limited randomized controlled trials of drugs in juvenile dermatomyositis (JDM), and treatment is largely based on lower-quality data such as case series, retrospective studies, and open-label prospective studies. These data have been compiled into expert recommendations or consensus treatment plans, which help guide therapy. While initial therapy is more standard with most including corticosteroids (high-dose oral and/or pulse intravenous methylprednisolone) and methotrexate, for refractory patients, guidelines are more varied with multiple options or combinations, including biologic therapies. There is a clear need for more efficacious and personalized therapy in JDM. Emerging treatment options worthy of further study in JDMinclude targetingIFN-signaling (JAK, IFNAR1, IFN beta),B-cells (CD20, CD19, BAFF, TACI, CD38, BCMA)including Chimeric Antigen Receptor (CAR)-T cell therapy, mitochondrial dysfunction, and NETs.

Factors influencing the discontinuation of biologic therapies in patients with ulcerative colitis

BackgroundThe therapeutic landscape for ulcerative colitis (UC) has recently broadened to include anti-TNFα, anti-integrin, and anti-IL-12/23p40 antibody agents. These biological agents are tailored to individual patient profiles. However, some patients cease biological treatment. This study investigates factors influencing the discontinuation of biological treatment in UC patients.MethodsThis retrospective single-cohort study encompasses UC patients who commenced treatment with biological agents like infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab from April 2019 to March 2022. Patients were categorized into continuation and discontinuation groups based on their one-year treatment status. Baseline characteristics were compared between the groups.ResultsOf the 116 UC patients, 102 were included in the study. Among these, 74 (72.5%) continued and 28 (27.5%) discontinued biological therapy. Discontinuation rates for infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab were 33.3%, 25.0%, 50.0%, 30.2%, and 15.6%, respectively. The primary discontinuation reason was lack of efficacy (85.7%), followed by adverse events (7.1%), pregnancy (3.6%), and death (3.6%). The discontinuation group had a significantly lower rate of concomitant thiopurine compared to the continuation group (28.6% vs. 56.8%, p = 0.0132). Multivariable analysis revealed that concomitant thiopurine was independently associated with therapy continuation (p = 0.0075).ConclusionThe study indicates that concomitant thiopurine significantly correlates with the continuation of biological therapies in UC patients, underscoring the importance of concomitant thiopurine in sustaining biological therapy. Further studies are warranted to assess the efficacy of combination therapy.

Efficacy of Second-Line Biological Therapies in Moderate to Severe Ulcerative Colitis Patients with Prior Failure of Anti-Tumor Necrosis Factor Therapy: A Multi-Center Study.

Few studies have compared the efficacy and safety of second-line biological therapies in ulcerative colitis (UC) patients with prior exposure to anti-tumor necrosis factor (TNF) therapy. We aim to compare the efficacy and safety between ustekinumab, vedolizumab, and tofacitinib, a current option as second-line biological therapy with different mechanisms in those patients. This retrospective multi-center study was conducted across five institutions from 2011 to 2022. We enrolled patients with moderate to severe UC who failed anti-TNF therapy and subsequently received ustekinumab, vedolizumab, or tofacitinib as second-line biological therapy. The outcomes were analyzed for clinical response/remission and endoscopic improvement/remission rates after induction therapy, drug persistency, and adverse events. A total of 70 UC patients were included and grouped into ustekinumab (11 patients), vedolizumab (40 patients), and tofacitinib (19 patients) treatments. The clinical response/remission rates after induction therapy were similar between ustekinumab (90.9/81.8%), vedolizumab (92.5/65.0%), and tofacitinib (94.7/73.7%). There were no significant differences in the endoscopic improvement/remission rates between the three groups: 90.9/18.2% for ustekinumab, 72.5/12.5% for vedolizumab, and 84.2/26.3% for tofacitinib. Drug persistence was similar across the three agents (p = 0.130). Three patients of the tofacitinib group experienced adverse events (herpes zoster and hypertriglyceridemia). Based on real-world data, second-line biological therapy with ustekinumab, vedolizumab, and tofacitinib showed comparable efficacy in patients with moderate to severe UC with prior exposure to anti-TNF therapy.

Muscle ultrasound in Spondyloarthritis patients receiving biologic disease-modifying anti-rheumatic drugs early in treatment

Objective: This study evaluated muscle ultrasound in spondyloarthritis (SpA) patients receiving biologic disease-modifying anti-rheumatic drugs (b-DMARDs) early in treatment. Methods: A prospective study was conducted with 110 b-DMARD-naive SpA patients. The baseline and control muscle strength, physical performance tests, ultrasonographic muscle parameters, and disease activity scores of 67 controlled patients were examined. Results: During the follow-up period, there were significant improvements in the thickness of the gastrocnemius medialis (GM) muscle (p<0.001), the length of the GM fascicle (p=0.031), the thickness of the rectus femoris (RF) muscle (p<0.001), the cross-sectional area of the RF (RFCSA) muscle (p<0.001), the thickness of the rectus abdominis (RA) muscle (p<0.001), the thickness of the transverse abdominis (TA) muscle (p=0.004), and the thickness of the external oblique (EO) muscle (p=0.042). Besides, ASDAS-CRP scores were related to GM muscle thickness, RFCSA, and TA muscle thickness percent changes in patients whose disease activity regressed from high to moderate (respectively; p=0.030, p=0.040, p=0.002). Conclusion: Muscle ultrasound examination can show muscle mass improvement in SpA patients during treatment.

Impact of biological therapies on clinical outcomes in patients with severe eosinophilic asthma with chronic rhinosinusitis: an observational study from Saudi Arabia

BackgroundWe aimed to study the impact of biological therapies in Saudi Arabia on patients with severe asthma (SA) combined with chronic rhinosinusitis (CRS) in terms of clinical outcomes.MethodsThis is a retrospective observational cohort research that was undertaken at the severe asthma clinics of the Armed Forces Hospital of the Southern Region (AFHSR) and King Khalid University Hospital, Abha, from March to September 2022 to delineate the effects of 3 biological therapies (dupilumab, benralizumab, and omalizumab) in adults with SA and concomitant CRS. Clinical outcomes assessed included asthma exacerbation frequency, hospitalization rates, use of oral corticosteroids (OCs), and the asthma control test (ACT) scores before and 1 year after biological therapies.ResultsEighty patients were enrolled, with a mean age of 46.68. There were 45 (56%) females and 35 (44%) males. There was a notifiable decrease in the frequency of exacerbations and hospitalization and in the number of patients who received OCs after 6 and 12 months of biological therapies compared to pre-biological therapies, respectively (p < 0.001 each), while there was a significant increase in the ACT scores at 6 and 12 months post-biological therapies, compared to pre-biological therapies, respectively (p < 0.001). These significant differences were maintained with all the 3 biologics used.ConclusionsResults from the first study from two large Saudi Arabian tertiary centers for patients with SA and CRS agree with and support those of worldwide real-life ones. One-year follow-up showed the effectiveness of the 3 drugs in terms of reduced frequency of asthma hospitalizations and exacerbations, the use of OCs, and improved ACT scores. Further prospective multicenter studies are warranted.

Pregnancy Outcomes from a Multidisciplinary Obstetric-Medicine/Rheumatology Clinic in the United States: A Five-Year Retrospective Analysis.

At Women & Infants Hospital in Providence, Rhode Island, the Specialty Care in Pregnancy clinic combines obstetric-medicine internists with rheumatologists to care for pregnant patients with rheumatologic conditions. These clinics are scarce, with only three known similar clinics in the United States. This study aims to characterize the population cared for in this clinic, identify interventions, and analyze pregnancy outcomes for the birthing parents and newborns. A five-year retrospective chart review was performed from January 1st, 2016, through December 31st, 2021. Of 81 patients, 62% had a clinically diagnosed rheumatic disorder. Of 87 patient visits, which included preconception, prenatal, and postpartum encounters, 54% of patients were taking conventional synthetic disease modifying antirheumatic drugs, and 17% were taking biologic disease modifying antirheumatic drugs. New medications were started in 52% of patients. A total of 52% of pregnancies resulted in live births, with 2% resulting in miscarriages. Prematurity occurred in 19% of newborns, and 9% had intrauterine growth restriction. Our study illustrates the benefits of multidisciplinary care in patients with rheumatologic disorders during their prenatal and perinatal periods. The expertise from both the obstetric-medicine internists and rheumatologists was critical in making complex decisions that weighed the benefits of therapy against potential risks for the fetus. Our multidisciplinary approach resulted in doubling of the number of patients initiating disease modifying therapy and increased prophylaxis with hydroxychloroquine and/or aspirin therapy, as recommended by current guidelines. Additional multidisciplinary clinics of this type would help coordinate care among physicians who frequently treat these high-risk, unique patients and open the door for more research of this understudied population.

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

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

Extracorporeal Photopheresis with 5-Aminolevulinic Acid in Crohn's Disease-A First-in-Human Phase I/II Study.

Background/Objectives: With the increasing prevalence of Crohn's disease (CD), treatment options for patients who fail conventional and advanced therapy are highly needed. Therefore, we explored the safety and efficacy of extracorporeal photopheresis (ECP) using 5-aminolevulinic acid (ALA) and blue light (405 nm). Methods: Patients with active CD who failed or were intolerant to biological therapy were eligible. Mononuclear cells (90 mL) were collected from each patient using a Spectra Optia® apheresis system and diluted with 100 mL of 0.9% sodium chloride in a collection bag. The cells were incubated with ALA at a concentration of 3 millimolar (mM) for 60 min ex vivo and illumination with an LED blue light (405 nm) source (BLUE-PIT®) before reinfusion to the patient. Recording of vital signs and adverse events were regularly performed. At week 13, we assessed the patients with colonoscopy, the Harvey Bradshaw Index (HBI), the Inflammatory Bowel disease Health Related Quality of Life Questionnaire, and the measurement of serum C-reactive protein and fecal calprotectin (FC) levels. Biopsies of the intestines were taken for immunohistochemistry. Results: Seven patients were included. Four patients completed the treatments, with a total of 24 treatments. Three of the four patients achieved a favorable response, including a lower HBI, lower FC levels, and/or endoscopic improvement. No significant adverse events were observed. The remaining three patients received only one, three, or five treatments due to technical difficulties, medical reasons, or the withdrawal of informed consent. Conclusions: ALA-based ECP appears safe and seems to give some clinical improvement for the patients with active CD who failed to respond to conventional and advanced therapies.

Metabolic Syndrome, Adipokines, and Response to Advanced Therapies in Rheumatoid Arthritis.

We determined if metabolic syndrome, its components, and adipokines (adiponectin, leptin, Fibroblast Growth Factor-21) were associated with response to advanced therapies among patients with rheumatoid arthritis (RA). This study included participants with RA initiating either TNFi or non-TNFi biologic therapies from the Comparative Effectiveness Registry to studyTherapies forArthritis andInflammatory Conditions(CERTAIN) cohort within the CorEvitas registry. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III definition. Adipokines were assessed on stored samples from a sub-sample of responders and non-responders (N=200). The primary outcome was the achievement of a change as large as the minimal clinically important difference (MCID) for the Clinical Disease Activity Index (CDAI) at 6 months. Among 2,368 participants, 687 (29%) had metabolic syndrome. Metabolic syndrome was associated with lower odds of achieving CDAI MCID [OR (95% CI): 0.69 (0.56,0.86) p=0.001] with a dose-dependent decrease in response rate according to the number of components present. Model fit was superior for metabolic syndrome compared to BMI. Associations between metabolic syndrome and MCID achievement were similar between patients receiving TNFi [OR (95% CI): 0.65 (0.49,0.87) p=0.003] v. non-TNF therapies [OR (95% CI): 0.76 (0.55,1.04) p=0.08)] (p-for-interaction=0.49). Adipokines were not associated with MCID achievement. Metabolic syndrome is associated with lower response rates with the initiation of an advanced therapy in RA, with similar effects for both TNFi and non-TNFi agents. Adipokines were strongly associated with metabolic syndrome but were not associated with clinical response.

Impact of surface tension, viscosity, pump settings, and nozzle size on filling process capability and accuracy in high-concentration biopharmaceuticals

Filling is the final critical unit operation in the manufacturing process of liquid biological drug products. This paper thoroughly investigates the influence and mechanisms of peristaltic pump settings, nozzle size, product surface tension and viscosity on the biopharmaceutical filling processes based on the established filling process model of surrogates. Our study highlights the significant role of pump settings in influencing filling process capability indexes, in addition to their primary function of regulating flow rate. Surface tension minimally impacts flow behavior but significantly regulates the final dropʼs behavior, with lower surface tension increasing dripping tendencies. Viscosity proves crucial; higher viscosity intensifies friction and head loss of filling flow in tube/nozzle, causing pressure and flow rate losses, more pronounced dripping, and worse filling accuracy. Furthermore, nozzle size moderates the impact of pump settings, surface tension, and viscosity on filling performance. Larger nozzles help mitigate these effects, contributing to enhanced stability in filling performance under challenging conditions. For high-concentration biopharmaceuticals with elevated viscosity during filling, utilizing larger nozzles and reducing pump speed could achieve enhanced Cpk values and improved filling accuracy. Understanding the complex interactions among these factors is vital for optimizing the biopharmaceutical industry, promoting cost-effective practices, and enhancing production efficiency.