Biologics Research Articles

Psycho-cognitive factors and adherence to disease-modifying biologic therapies in patients with rheumatoid arthritis: A cross-sectional study

Psycho-cognitive factors and adherence to disease-modifying biologic therapies in patients with rheumatoid arthritis: A cross-sectional study

Improvement in rheumatoid sarcopenia with biological therapy; muscle ultrasound study

Improvement in rheumatoid sarcopenia with biological therapy; muscle ultrasound study

Characteristics and Genomic Localization of Nurse Shark (Ginglymostoma cirratum) IgNAR

The variable domain of IgNAR shows great potential in biological medicine and therapy. IgNAR has been discovered in sharks and rays, with the nurse shark (Ginglymostoma cirratum) IgNARs being the most extensively studied among sharks. Despite being identified in nurse sharks over 30 years ago, the characteristics and genomic localization of IgNAR remain poorly defined, with significant gaps even in the latest released genome data. In our research, we localized the IgNAR loci in the nurse shark genome and resolved the previously missing regions. We identified three IgNAR loci, designated GcIgNAR1, GcIgNAR2, and GcIgNAR3, with only GcIgNAR1 and GcIgNAR2 being expressed. GcIgNAR1 and GcIgNAR2 belong to type I and type II IgNARs, respectively, and each exhibits several different isoforms. Most nurse shark IgNARs possess five constant domains. However, we found transcripts of GcIgNAR1 and GcIgNAR2 lacking two constant domains, C4 and C5, which differ from the IgNAR of the whitespotted bamboo shark. The protein structures of GcIgNAR1 and GcIgNAR2, generated by AlphaFold3, confirmed the accuracy of the IgNAR loci we identified. Our findings advance scientific understanding of IgNAR in nurse sharks and facilitate future research and medical applications.

Comprehensive analysis of rheumatic diseases, comorbidities, and mortality in geriatric population: Real-world data of 515 patients in a single rheumatology clinic.

Rheumatic diseases present unique challenges in the elderly, with changes in the immune system contributing to varied clinical presentations. More individuals are now living with chronic diseases due to greater life expectancy, but there is a lack of real-world data about rheumatic diseases and comorbidities in older people. This study aimed to investigate disease types, comorbidities, treatments, and mortality in geriatric patients in comparison to non-geriatric patients at a rheumatology clinic. This retrospective observational cohort study reviewed the medical records of 2610 patients from January 2021 to January 2024 at 2 branches of a private hospital's rheumatology clinics. Demographic information and data on rheumatic diseases, noninflammatory conditions, treatments, comorbidities, and mortality were collected, and geriatric patients were compared to non-geriatric patients. Geriatric patients (n = 515) had a significantly higher prevalence of rheumatoid arthritis (50.6% vs 28.8%, P < .001), polymyalgia rheumatica (11.1% vs 0.2%, P < .001), and crystal arthritis (19.6% vs 8.8%, P < .001), with more frequent geriatric-onset cases. Osteoarthritis was also more prevalent in geriatric patients (51.2% vs 11.3%, P < .001), while fibromyalgia was more common in the non-geriatric group (15.9% vs 4.1%, P < .001). Geriatric patients experienced higher rates of comorbidities, including hypertension (72.4% vs 17.8%, P < .001), diabetes (33.6% vs 12.1%, P < .001), and osteoporosis (64.9% vs 35.4%, P < .001). These patients used more corticosteroids (74.5% vs 44%, P < .001), and conventional synthetic disease-modifying antirheumatic drugs (62.4% vs 49.4%, P < .001) but fewer biological disease-modifying antirheumatic drugs (9.2% vs 23.1%, P < .001). Mortality rates were significantly higher in geriatric patients (6% vs 0.3%), with cancer (P = .001), ischemic heart disease (P = .04), heart failure (P = .01), chronic kidney disease (P = .02), and interstitial lung disease (P = .01) being associated with increased mortality. Geriatric rheumatology should receive greater focus in future research to help address the anticipated increases in demand and to develop tailored management strategies for elderly patients with rheumatic diseases and comorbidities.

Psoriatic arthritis (literature review)

Psoriatic arthritis (PsA) is a chronic immune-inflammatory progressive disease of the musculoskeletal system observed in psoriasis, which affects the joints, spine and entheses; it occurs in the form of arthritis, dactylitis, enthesitis, and can also manifest as spondylitis or sacroiliitis. The etiology of PsA is unknown, but the pathogenesis has been studied in more detail. Under the influence of external factors, such as infectious agents (viruses, bacteria, fungi), neuropsychic stress, injuries, drugs, changes in intestinal microbiota, etc., genetically predisposed individuals experience activation of the immune system, both congenital and acquired. Currently, there are 5 clinical forms of PsA: predominantly lesion of the distal interphalangeal joints of the hands and feet, distal form; mutilating arthritis; psoriatic spondylitis; asymmetric mono-oligoarthritis; symmetrical polyarthritis, rheumatoid-like form. Along with the characteristic symptomsof skin and joint damage, patients with PsA note a decrease in the quality of life, general malaise, fever, enlarged lymph Review nodes, weight loss, signs of comorbid pathology (obesity, diabetes, cardiovascular diseases). Arthritis is accompanied by tendinitis, synovitis, enthesitis. Isolated spinal damage (psoriatic spondylitis) is rare, it is usually combined with peripheral arthritis, characterized by pain in the spine, dysfunction, curvature. Differential diagnostics are carried out with rheumatoid arthritis, gout, ankylosing spondylitis, polyosteoarthritis, infectious forms of joint damage, joint damage in chronic inflammatory bowel diseases. Treatment of PsA should include medication, physiotherapy and spa treatment. Usually, treatment of PsA begins with the use of such drugs as methotrexate, leflunomide, sulfasalazine, cyclosporine A; non-steroidal anti-inflammatory drugs and intra-articular administration of glucocorticosteroids are used as an auxiliary agent, they are classified as symptom-modifying drugs, they partially improve the patient’s quality of life, reduce pain, but have little effect on the progression of the pathological process. In the absence of an effect from previously conducted treatment and contraindications, genetically engineered biological drugs are used.

Upadacitinib for Induction of Remission in Pediatric Ulcerative Colitis: An International Multi‑center Study.

Data on upadacitinib therapy in children with ulcerative colitis (UC) or unclassified inflammatory bowel disease (IBD-U) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as an induction therapy in pediatric UC or IBD-U. In this multicenter retrospective study, children treated with upadacitinib for induction of remission of active UC or IBD-U from 30 centers worldwide were enrolled. Demographic, clinical and laboratory data as well as adverse events (AEs) were recorded at week 8 post induction. One hundred children were included (90 UC and 10 IBD-U, median age 15.6 [interquartile range 13.3-17.1] years). Ninety-eight were previously treated with biologic therapies, and 76 were treated with ≥2 biologics. At the end of the 8-week induction period, clinical response, clinical remission, and corticosteroid-free clinical remission (CFR) were observed in 84%, 62%, and 56% of the children, respectively. Normal C-reactive protein and fecal calprotectin (FC) <150 mcg/g were achieved in 75% and 50%, respectively. Combined CFR and FC remission was observed in 18/46 (39%) children with available data at 8 weeks. AEs were recorded in 37 children, including one serious AE of an appendiceal neuroendocrine tumor. The most frequent AEs were hyperlipidemia (n=13), acne (n=12), and infections (n=10, five of whom with herpes viruses). Upadacitinib is an effective induction therapy for refractory pediatric UC and IBD-U. Efficacy should be weighed against the potential risks of AEs.

Circulating Fetuin-A concentrations in rheumatic diseases: asystematic review and meta-analysis.

Rheumatic diseases (RDs) include a broad group of disabling conditions with different phenotypes, from autoimmune to autoinflammatory, degenerative, metabolic or mixed manifestations. With the continuous efforts to identify therapeutic targets for new biologic drugs to treat overt clinical manifestations, research is also focusing on the discovery of new biomarkers to diagnose and manage early disease stages. In this context, we conducted a systematic review and meta-analysis of Fetuin-A (FtA), a glycoprotein synthesized by the liver that participates in several biological processes and has been proposed as a biomarker for several disorders, including rheumatoid arthritis. A systematic search in PubMed, Scopus and Web of Science, from inception to the 24th of August 2024, led to the identification of 13 manuscripts from 219 records; six additional studies were identified through reference hand-search, for a total of 19 studies. There was a significant decrease in FtA concentrations in RD patients (standardized mean difference, SMD = -.91; 95% CI -1.43 to -.39, p = .001), with no substantial contribution from any individual study nor publication bias. The effect size was significantly associated with erythrocyte sedimentation rate, various lipid fractions, geographical area of study conduction, study design and specific type of RD. In conclusion, our study identified significant reductions in FtA concentrations in RD patients versus healthy controls. These alterations were significantly associated with specific study and patient characteristics. Further research is required to identify the exact pathophysiological mechanisms underlying these alterations and the possible utility of measuring FtA for the diagnosis and management of RDs.

Clinical effect of Secuchiumab in the Treatment of Psoriasis

Psoriasis is a chronic and recurrent skin condition triggered by the immune system, with a relatively high prevalence. The primary clinical manifestation of this condition is the appearance of red and swollen patches of skin covered with silvery scales, often accompanied by itching and a feeling of tightness. In addition to skin symptoms, psoriasis patients frequently experience systemic conditions such as arthritis and heart disease. Recent research has shown a strong link between psoriasis and metabolic syndrome. The main symptoms of metabolic syndrome include hypertension, high blood sugar, elevated cholesterol levels, and abdominal obesity. These issues not only increase the risk of cardiovascular diseases but may also exacerbate the severity of psoriasis. Traditional treatments for psoriasis have included topical medications, phototherapy, and symptomatic relief therapies, with methotrexate being a common drug. While these conventional methods can partially improve the skin condition of psoriasis patients with metabolic syndrome, they are not effective at modulating immune system function or correcting metabolic imbalances. As our understanding of the pathophysiology of psoriasis deepens, biologic therapies have increasingly become a research focus. Secukinumab, a monoclonal antibody targeting interleukin-23, inhibits specific inflammatory pathways and offers a new, potentially more effective treatment option for psoriasis patients with metabolic syndrome.

Clinical Course of Isolated Recurrent, Persistent Complex Perianal Fistulas without Luminal Crohn’s Disease: A Multicenter Case Series of 24 Patients

Abstract Background Isolated complex perianal fistulas, without luminal evidence of inflammatory bowel disease in the gastrointestinal tract, pose diagnostic and treatment dilemmas for gastroenterologists and colorectal surgeons. For patients who develop recurrent complex fistulas, a presumptive diagnosis of Crohn’s disease may be made. It is unclear whether these cases of isolated perianal disease in the absence of luminal inflammation truly represent isolated severe cryptoglandular fistulas or rather an early presentation of Crohn’s disease. We aimed to investigate the clinical course and outcomes of patients with isolated complex perianal fistulas. Methods In this retrospective multicenter case series across six institutions in the United States, we report the clinical course of patients with isolated recurrent complex perianal fistulas, including their diagnostic evaluation, medical and surgical therapies, and clinical outcomes. Results All patients (n=24) required incision and drainage of perirectal abscesses. The majority received setons (n=19, 79%), more intensive surgical interventions (n=15, 62.5%; including fistulotomy/sphincterotomy, advancement flap, and ligation of the intersphincteric fistula tract), antibiotics (n=17, 71%), and biologic therapy (n=16, 67%). Nine patients (37.5%) underwent a combined medical-surgical approach with biologics and intensive surgical intervention. Despite surgical and/or medical management, active symptomatic complex perianal fistulas persisted in 58% (n=14) of patients at follow-up (median 5.5 years, interquartile range 2.5-10 years); symptom remission was achieved in 21% (n=5), and fistula closure in 21% (n=5). Conclusions These cases highlight a multidisciplinary and multimodal approach when treating isolated complex perianal fistulas, and their propensity to persist despite the incorporation of advanced therapies.

Clinical and morphological features of corneal lymphoma in 26 horses (27 eyes).

Little information describing the biologic behaviour and therapies for corneal lymphoma exist. To characterise histologically confirmed equine corneal lymphoma considering breed, age or sex predisposition, histologic and immunologic features, therapies and outcomes. Retrospective case series. A multicentre retrospective medical record review was used to identify horses that presented with corneal disease confirmed morphologically as corneal lymphoma from 2012 to 2022. Mean age at diagnosis was 10.5 years. Males represented 18/26 cases. Warmblood (14) and Thoroughbred (6) breeds were most commonly represented. 25/26 had unilateral ocular involvement. No cases had evidence of multicentric lymphoma. Most eyes (77.7%) had a history of suspected immune-mediated keratitis (IMMK) or eosinophilic keratitis. Morphological diagnosis confirming lymphoma was available for all cases. B-cell lymphoma was diagnosed in 19/24 eyes for which immunohistochemistry was performed, with intermediate to large B-cell lymphoma being most common. Fifteen of 27 eyes received at least one form of adjunctive therapy following keratectomy. Four eyes, which did not receive adjunctive therapy following keratectomy, experienced recurrence. No horses treated with adjunctive therapy following keratectomy experienced recurrence. Malignant transformation of IMMK to lymphoma was morphologically documented in one eye and suspected in three others based on recurrence of clinical signs. All globes were retained and visualised at the last follow-up. Incomplete medical records, owner subjectivity concerning onset of disease and cases being lost to follow-up. Malignant transformation of IMMK to corneal lymphoma likely occurs in horses. Lymphoma should be a differential for nonulcerative keratitis in horses. Keratectomy and histopathology may be considered in progressive or refractory cases of IMMK to rule out neoplastic disease. Recurrence of corneal lymphoma is unlikely following excision and adjunctive therapy. Cases with large corneal surface area or deep stromal involvement may have a likelihood for recurrence.

Development and external validation of a prediction model for the risk of relapse in psoriasis after discontinuation of biologics

BackgroundSome patients with psoriasis experience relapses shortly after discontinuation of biologics. However, there is a lack of risk prediction tools to identify those at high risk of relapse.ObjectiveTo develop and validate a risk prediction model for psoriasis relapse after biologics discontinuation.MethodsPublications from PubMed, EMBASE, Medline, and the Cochrane Library were systematically searched and meta-analyses were conducted to identify risk factors for psoriasis relapse after biologics discontinuation. Statistically significant risk factors were identified and used to create a risk assessment model weighted by the impact of each factor. The model was externally validated using a cohort of 416 Chinese psoriasis patients.ResultsEight studies (N = 2066) were included in the meta-analysis. Body mass index (BMI), smoking, disease duration, comorbid psoriatic arthritis (PsA), remission speed and extent during treatment, history of biologic therapy, and therapy duration were identified as correlates of relapse in the meta-analysis and were incorporated into the prediction model. The median age of the 416 patients in the validation cohort was 41.5 (IQR 32, 53) years, with 63% male, and a baseline PASI score of 15.4 (IQR 10.5, 21). It was verified that the area under the curve (AUC) of the prediction model was 0.796 (95% CI, 0.753–0.839), with an optimal cut-off value of 11.25 points, sensitivity of 65.1%, and specificity of 82.2%.ConclusionMultivariate models using available clinical parameters can predict relapse risk in psoriasis patients after biologics discontinuation. Early individual identification of patients at risk of relapse, and screening of candidate cohorts for long-term treatment or dose reduction may benefit both patients and physicians.

Защита вишни от коккомикоза в Республике Татарстан

The purpose of the research was a comparative assessment of the use of the biological drug Bactofit and the chemical drug Skor in protecting varieties of sour cherry from coccomycosis in the Republic of Tatarstan. The objects of study were varieties of ordinary cherry (Prunus cerasus L.) Nizhnekamskaya – early ripening, Shakirovskaya – medium ripening and Obil,naya – late ripening. Sour cherry plants were treated after the end of flowering, after 6 p.m. with the biological drug Bactofit 4 times after 7 days, with the chemical drug Skor – 2 times after 14 days. The concentration of the Skor solution was 2 ml/10 l, Bactofit – 30 ml/10 l. The control sour cherry plants were not treated with drugs. The growing seasons of 2020-2021 were dry. In 2020, the hydrothermal coefficient (GTC) for the growing season was 0.64, for the summer period – 0.57. GTC for the growing season of 2021 was 0.48, for the summer months – 0.19. In the Republic of Tatarstan in 2020-2021, the Nizhnekamskaya cherry variety (25%) was affected by coccomycosis less than the Shakirovskaya (36.7%) and Obil,naya (30%) varieties. The biological effectiveness of the chemical preparation Skor (67.3%) is higher than the biological preparation Bactofit (59.2%). The share of the influence of drugs on the incidence of cherry leaves with coccomycosis is 38.2%, the share of the influence of varieties is 3.2%, the share of the influence of head conditions is 0.2%, the share of the influence of the interaction of drugs with varieties is 29.5%, the share of the influence of the interaction of drugs with the conditions of the year is 3.7%, the share of the influence of the interaction of varieties with the conditions of the year is 9.8%, the share of the effect of the interaction of drugs, varieties and conditions of the year – 13.0%. The development of coccomycosis on sour cherry leaves on average for 2020-2021 ranged from 14.9% in the Nizhnekamskaya variety to 25.5% in the Shakirovskaya variety. The disease has received significantly less development when processing sour cherry plants with the chemical preparation Skor. The treatment of plants of the Nizhnekamskaya variety with the chemical preparation Skor gives the greatest, reliable increase in productivity. In sour cherry breeding for resistance to coccomycosis, it is recommended to use the Nizhnekamskaya variety.

Biologic Medications for Severe Asthma: Implications for Understanding Pathogenic Heterogeneity and Endotypes

Biologic Medications for Severe Asthma: Implications for Understanding Pathogenic Heterogeneity and Endotypes

Immunological Profiles, Oxidative Stress Biomarkers and Plasma Cholinesterase Activities in Patients with Immune-Mediated Inflammatory Diseases Treated in a Clinic in Duhok, Iraq

Abstract Aim The purpose of the present study was to measure the levels of selected plasma biochemical variables among cases of immune-mediated inflammatory diseases (IMIDs), other than rheumatoid arthritis, treated in a clinic in the city of Duhok, Iraq, since such information is scarce in the region. Materials and Methods A case-control study on IMIDs patients treated in a clinic in Duhok, Iraq, was performed from February 2022 to June 2023. A total of 29 patients of both genders with IMIDs and 61 healthy controls were recruited at the Duhok Center for Rheumatic Diseases and Medical Rehabilitation, Duhok, Iraq. The laboratory tests conducted on plasma samples from IMIDs patients and healthy controls included measurements of interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, malondialdehyde (MDA), total antioxidant status (TAS) and cholinesterase (ChE) activity. Results No significant differences were found in gender distribution, age, and body mass index between the IMIDs patients and healthy controls. The majority of patients (69%) received conventional therapy combined with biologic agents, whereas the remaining patients (31%) received only conventional medications. The IMIDs identified among the 29 patients were Behcet’s disease (27.6%), ankylosing spondylitis (24.1%), inflammatory bowel diseases (24.1%), psoriatic arthritis (10.3%), systemic lupus erythematosus (6.9%) and psoriasis (6.9%). Conventional therapy used was mostly azathioprine (44.8%) and methotrexate (17.2%), whereas biological therapy included mostly etanercept (27.6%) and adalimumab (24.1%). The values of CRP, IL-6 and TNF-Į among the IMIDs patients were not significantly different from those of the controls. The oxidative stress biomarker MDA was elevated in IMID patients (2.93 ± 1.106 —mol/L vs. 2.52 ± 0.478) at a p value of 0.064 (though not significant). The TAS level (1.21 ± 0.422 mmol Trolox Equiv./L vs. 1.00 ± 0.338, p = 0.022) and plasma ChE activity (1.18 ± 0.50 ¨ pH/20 min vs. 0.83 ± 0.30, p = 0.001) were significantly higher in IMIDs patients compared to controls. Conclusions The data suggest that oxidative stress and changes in plasma ChE activity might be a part of the pathophysiological alterations among IMIDs patients. Therapeutic drug monitoring and its clinical outcome as well as response of IMIDs patients to anti-ChE agents are worth of further in depth exploration and pursuing. They are essential for better diagnosis, treatment, and management of IMIDs.

The Use of Tissue Concentrations of Biological and Small-Molecule Therapies in Clinical Studies of Inflammatory Bowel Diseases

The Use of Tissue Concentrations of Biological and Small-Molecule Therapies in Clinical Studies of Inflammatory Bowel Diseases

Overview of Achilles Tendon Injury Treatments

Achilles tendon injuries, common among athletes and individuals engaged in high-impact activities, present significant challenges in both diagnosis and treatment. This article describes the Achilles tendon as a whole, the nature of related injuries, and how they are diagnosed and treated and how they are diagnosed, often magnetic resonance imaging (MRI) and ultrasound play crucial roles in differentiating the severity of these injuries. Treatment approaches range from non-surgical options, like functional bracing and physical therapy, to surgical interventions necessary for complete ruptures. Emerging biological therapies, it includes Platelet-Rich Plasma (PRP) and stem cell tech, show promise in enhancing recovery, though another research is needed to confirm their years effectiveness. Additionally, preventive measures and personalized rehabilitation programs are emphasized as essential strategies for reducing the incidence of Achilles tendon injuries and ensuring effective recovery. The paper concludes by discussing the future direction of treatment modalities, highlighting the potential of advanced technologies and therapies in improving patient outcomes.

Dupilumab Treatment for Aspirin-Exacerbated Respiratory Disease in a Real-World Setting: Impact on Quality of Life and Healthcare Utilization.

Patients with aspirin-exacerbated respiratory disease (AERD) have difficult-to-treat asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) and often require treatment with biologic therapy for asthma or CRSwNP. Healthcare utilization in patients with AERD has not been well described since the advent of respiratory biologics. To determine real-world healthcare utilization and quality of life among patients with AERD and to understand the impact of dupilumab, a monoclonal antibody targeting the interleukin 4 receptor, on patient-reported health outcomes and healthcare utilization. We conducted a longitudinal survey study of 98 patients with AERD recruited from the Brigham and Women's Hospital AERD registry. Patients completed online questionnaires describing their medication history, healthcare utilization, and quality of life every 3 months for 2 years. At the end of 24 months, participants who were on dupilumab at the start of the study and those who started dupilumab had a significant reduction in the number of reported poor health days in the preceding month compared to patients not on dupilumab (P < .001 and P < .01, respectively). Participants on dupilumab and those who started dupilumab also had significantly lower overall sinonasal outcome test-22 and asthma control test scores compared to those not on dupilumab over 24 months (P < .05 for both groups). Dupilumab therapy significantly improves health-related quality of life in patients with AERD, specifically as it pertains to patient assessment of days of overall poor health and quality of life related to sinonasal and asthma symptoms.

Clinical features and natural course of Hidradenitis Suppurativa in Turkey: a multicentre study.

The natural history, the progression of a disease process in an individual over time, has not yet been fully elucidated in hidradenitis suppurativa (HS). In this large multicenter study, we aimed to investigate the natural history of HS and its gender differences. This cross sectional study included 827 patients. The chronological order of the clinical manifestations for each patient were recorded retrospectively. Sociodemographic characteristics, triggering factors, clinical, treatment, and prognostic features were also evaluated. The mean age of disease onset was significantly younger in women than in men (22.42±9.28 vs. 27.06±20.56, p<0.001) and those with a family history (p<0.0001). The mean disease duration was 91.17±83.64 months. The most common symptom was purulent discharge (81%). The mean duration of abscess was shorter in women than in men (3.11±2.65 vs. 3.75±3.75, p=0.01). The axilla was the most common onset area followed by the inguinal and gluteal regions. The disease ran a more severe course in men. Abscess/inflammatory nodule was defined in the last 6 months in 88.6% of the patients; however, the first 5 years of the disease were the most active disease period in 67.5% of the patients. Multivariate analysis revealed being male, older age, family history, involvement of the axillary, inguinal and perianal regions independently associated with HS severity. While antibiotic use was the most important factor in improving the disease symptoms, stress was the most common aggravating factor. Biological therapy in men, laser epilation and pregnancy in women were significant alleviating factors. Whereas, weight gain was a more common aggravating factor for women. HS shows a relentlessly progressive course with inflammatory attacks, but the first years of the disease are the most active period. This study confirms that environmental and hormonal factors may play an important role in the disease course, probably with other endogenous or exogenous factors.

An Educational Digital Tool to Improve the Implementation of Switching to a Biosimilar (Rapid Switch Trainer): Tool Development and Validation Study.

Switching to biosimilars is an effective and safe practice in treating inflammatory diseases; however, a nocebo effect may arise as a result of the way in which the switch is communicated to a given patient. We aimed to design a gaming-based digital educational tool (including a discussion algorithm) to support the training of health care professionals in efficiently communicating the switch to biosimilars, minimizing the generation of a nocebo effect and thus serving as an implementation strategy for the recommended switch. The tool was developed based on interviews and focus group discussions with key stakeholders, both patients and health care professionals. Messages likely to either generate trust or to trigger a nocebo effect were generated on the basis of the interviews and focus group discussions. A total 7 clinicians and 4 nurses specializing in rheumatology, gastroenterology, and dermatology, with balanced levels of responsibility and experience, as well as balance between geographic regions, participated in the structured direct interviews and provided a list of arguments they commonly used, or saw used, to justify the switching, and objections given by the patients they attended. Patients with immune-mediated inflammatory diseases who were taking biologic drugs with (n=4) and without (n=5) experience in switching attended the focus groups and interviews. Major topics of discussion were the reason for the change, the nature of biosimilars, and their quality, safety, efficacy, and cost. Based on these discussions, a list of objections and of potential arguments was produced. Patients and health care professionals rated the arguments for their potential to evoke trust or a nocebo effect. Two sets of arguments, related to savings and sustainability, showed discrepant ratings between patients and health care professionals. Objections and arguments were organized by categories and incorporated into the tool as algorithms. The educators then developed additional arguments (with inadequate answers) to complement the valid ones worked on in the focus groups. The tool was then developed as a collection of clinical situations or vignettes that appear randomly to the user, who then has to choose an argument to counteract the given objections. After each interaction, the tool provides feedback. The tool was further supported by accredited medical training on biosimilars and switching. We have developed a digital training tool to improve communication on switching to biosimilars in the clinic and prevent a nocebo effect based on broad and in-depth experiences of patients and health care professionals. The validation of this implementation strategy is ongoing.

Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study.

Mirikizumab, a humanised monoclonal antibody that inhibits IL-23p19, is effective in moderate-to-severe ulcerative colitis. We aimed to evaluate the efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn's disease. VIVID-1 was a global phase 3, randomised, double-blind, double-dummy, placebo-controlled and active-controlled, treat-through study. The study enrolled adult patients at 324 sites (hospitals or medical centres, clinical practices, and clinical research sites) in 33 countries across Europe, Asia, North America, Central America, South America, and Australia. Adult patients with moderately-to-severely active Crohn's disease and previous inadequate response, loss of response, or intolerance to one or more approved biological therapies or conventional therapies were randomly assigned 6:3:2 to receive mirikizumab 900 mg intravenously at weeks 0, 4, and 8, then 300 mg subcutaneously every 4 weeks from weeks 12 to 52; ustekinumab about 6 mg/kg intravenously at week 0, then 90 mg subcutaneously every 8 weeks from weeks 8 to 52; or placebo. The coprimary endpoints assessing superiority of mirikizumab over placebo were composite endpoints: patient-reported outcome (PRO) clinical response at week 12 and endoscopic response at week 52 (endoscopic response-composite), and PRO clinical response at week 12 and Crohn's Disease Activity Index (CDAI) clinical remission at week 52 (CDAI clinical remission-composite). The adjusted risk differences were calculated, and the comparison was performed by the Cochran-Mantel-Haenszel test. Non-responder imputation was used. VIVID-1 was registered on ClinicalTrials.gov, NCT03926130, and is now complete. Between July 23, 2019, and Aug 23, 2023, 1150 patients were randomly assigned and received study treatment (safety population); 1065 patients were included in the efficacy population and received mirikizumab (n=579), ustekinumab (n=287), or placebo (n=199). Both coprimary endpoints were met: endoscopic response-composite was reached in 220 (38·0%) of 579 patients on mirikizumab versus 18 (9·0%) of 199 on placebo (99·5% CI 20·6-36·8; p<0·0001); CDAI clinical remission-composite was reached in 263 (45·4%) of 579 patients on mirikizumab versus 39 (19·6%) of 199 patients on placebo (99·5% CI 15·9-35·6; p<0·0001). The incidence rates of overall adverse events and discontinuations in patients treated with mirikizumab were lower compared with placebo. The most common adverse event across the three groups was COVID-19. Serious adverse events were reported in 65 (10·3%) of 630 patients on mirikizumab, 33 (10·7%) of 309 patients on ustekinumab, and 36 (17·1%) of 211 patients on placebo. There were three deaths during VIVID-1, one in the ustekinumab group, and two in the placebo group, including one in a placebo non-responder who switched to mirikizumab after week 12. None of the deaths were considered related to the study drug. The safety of mirikizumab in Crohn's disease was consistent with its known favourable profile. Mirikizumab was safe and effective as induction and maintenance treatment for patients with moderately-to-severely active Crohn's disease who had intolerance, inadequate response, or loss of response to standard therapy. Eli Lilly and Company.