Multicenter Cohort Study of Infliximab Pharmacokinetics and Therapy Response in Pediatric Acute Severe Ulcerative Colitis.

BACKGROUND & AIMS: We aimed to model infliximab (IFX) pharmacokinetics (PK) in pediatric acute severe ulcerative colitis (ASUC) and assess the association between PK parameters, including drug exposure, and clinical response. METHODS: We studied a multicenter prospective cohort of hospitalized children initiating IFX for ASUC or IBD-unclassified. Serial IFX serum concentrations over 26 weeks were used to develop a PK model. We tested the association of PK parameter estimates with day 7 clinical response, week 8 clinical remission, week 26 corticosteroid-free clinical remission (CSF-CR) (using the Pediatric Ulcerative Colitis Activity Index), and colectomy-free survival. RESULTS: Thirty-eight participants received IFX (median initial dose, 9.9 mg/kg). Day 7 clinical response, week 8 clinical remission, and week 26 CSF-CR occurred in 71%, 55%, and 43%, respectively. Albumin, C-reactive protein, white blood cell count, platelets, weight, and antibodies to IFX were significant covariates incorporated into a PK model. Week 26 non-remitters exhibited faster IFX clearance than remitters (P = .013). However, cumulative IFX exposure did not differ between clinical response groups. One (2.7%) and 4 (10.8%) participants underwent colectomy by week 26 and 2 years, respectively. Day 3 IFX clearance >0.02 L/h was associated with colectomy (hazard ratio, 58.2; 95% confidence interval, 6.0-568.6; P < .001). CONCLUSIONS: At median higher-than-label IFX dosing for pediatric ASUC, baseline faster IFX CL was associated with colectomy and at week 26 with lack of CSF-CR. IFX exposure was not predictive of clinical outcomes. Higher IFX dosing may sufficiently optimize early outcomes in pediatric ASUC. Larger studies are warranted to determine whether sustained intensification can overcome rapid clearance and improve later outcomes. CLINICALTRIALS: gov identifier: NCT02799615.

Preparation of protein-loaded nanoparticles based on poly(succinimide)-oleylamine for sustained protein release: a two-step nanoprecipitation method.

Currently, the treatment for acute disease encompasses the use of various biological drugs (BDs). However, the utilisation of BDs is limited due to their rapid clearance and non-specific accumulation in unwanted sites, resulting in a lack of therapeutic efficacy together with adverse effects. While nanoparticles are considered good candidates to resolve this problem, some available polymeric carriers for BDs were mainly designed for long-term sustained release. Thus, there is a need to explore new polymeric carriers for the acute disease phase that requires sustained release of BDs over a short period, for example for thrombolysis and infection. Poly(succinimide)-oleylamine (PSI-OA), a biocompatible polymer with a tuneable dissolution profile, represents a promising strategy for loading BDs for sustained release within a 48-h period. In this work, we developed a two-step nanoprecipitation method to load the model protein (e.g. bovine serum albumin and lipase) on PSI-OA. The characteristics of the nanoparticles were assessed based on various loading parameters, such as concentration, stirring rate, flow rate, volume ratio, dissolution and release of the protein. The optimised NPs displayed a size within 200 nm that is suitable for vasculature delivery to the target sites. These findings suggest that PSI-OA can be employed as a carrier for BDs for applications that require sustained release over a short period.

90K/Mac-2 BP Is a New Predictive Biomarker of Response to Infliximab Therapy in IBD Patients.

Inflammatory bowel diseases (IBD), comprising Crohn's disease (CD) and Ulcerative Colitis (UC), are multifactorial disorders characterized by a chronic inflammatory status with the secretion of cytokines and immune mediators. Biologic drugs targeting pro-inflammatory cytokines, such as infliximab, are broadly used in the treatment of IBD patients, but some patients lose responsiveness after an initial success. The research into new biomarkers is crucial for advancing personalized therapies and monitoring the response to biologics. The aim of this single center, observational study is to analyze the relationship between serum levels of 90K/Mac-2 BP and the response to infliximab, in a cohort of 48 IBD patients (30 CD and 18 UC), enrolled from February 2017 to December 2018. In our IBD cohort, high 90K serum levels were found at baseline in patients who then developed anti-infliximab antibodies at the fifth infusion (22 weeks after the first), becoming non-responders (9.76 ± 4.65 µg/mL compared to 6.53 ± 3.29 µg/mL in responder patients, p = 0.005). This difference was significant in the total cohort and in CD, but not significant in UC. We then analyzed the relationship between serum levels of 90K, C-reactive protein (CRP), and Fecal calprotectin. A significant positive correlation was found at baseline between 90K and CRP, the most common serum inflammation marker (R = 0.42, p = 0.0032). We concluded that circulating 90K could be considered a new non-invasive biomarker for monitoring the response to infliximab. Furthermore, 90K serum level determination, before the first infliximab infusion, in association with other inflammatory markers such as CRP, could assist in the choice of biologics for the treatment of IBD patients, thereby obviating the need for a drug switch due to loss of response, and so improving clinical practice and patient care.

Host cell in vivo production of the synthetic drug anti-CD25/IL-10 using minicircle vector.

Synthetic biologic drugs are highly successful for induction therapy in transplantation, but the development of novel biologics is limited because of the high cost of synthesis and purification. In this study, we developed a novel strategy for the production of synthetic protein drugs in vivo by the host itself. We utilized minicircle (MC) technology, which can robustly express a target molecule and secrete it from cells, as an indirect method to produce a protein of interest in vivo. We designed an MC vector containing the sequences of basiliximab (anti-CD25 mAb) and IL-10. We verified the substantial production of the anti-CD25/IL-10 protein from the MC in vitro and in vivo. The therapeutic effect of MC-derived anti-CD25/IL-10 was evaluated in a skin allograft mouse model by single intravenous infusion. Mice treated with the MC encoding anti-CD25/IL-10 exhibited prolonged skin allograft survival times accompanied by improved histologic changes and immunologic regulation. These findings indicate that the anti-CD25/IL-10 protein drug obtained by MC technology is functionally active and relevant for reducing allograft rejection. This self-reproducible strategy for synthetic protein drugs using MCs is a promising tool for transplantation.-Lim, S. W., Shin, Y. J., Luo, K., Quan, Y., Ko, E. J., Chung, B. H., Yang, C. W. Host cell in vivo production of the synthetic drug anti-CD25/IL-10 using minicircle vector.

Biochemical properties and oxalate-degrading activity of oxalate decarboxylase from bacillus subtilis at neutral pH.

Oxalate decarboxylase (OxDC) from Bacillus subtilis is a Mn-dependent hexameric enzyme that converts oxalate to carbon dioxide and formate. OxDC has greatly attracted the interest of the scientific community, mainly due to its biotechnological and medical applications in particular for the treatment of hyperoxaluria, a group of pathologic conditions caused by oxalate accumulation. The enzyme has an acidic optimum pH, but most of its applications involve processes occurring at neutral pH. Nevertheless, a detailed biochemical characterization of the enzyme at neutral pH is lacking. Here, we compared the structural-functional properties at acidic and neutral pH of wild-type OxDC and of a mutant form, called OxDC-DSSN, bearing four amino acid substitutions in the lid (Ser161-to-Asp, Glu162-to-Ser, Asn163-toSer, and Ser164-to-Asn) that improve the oxalate oxidase activity and almost abolish the decarboxylase activity. We found that both enzymatic forms do not undergo major structural changes as a function of pH, although OxDC-DSSN displays an increased tendency to aggregation, which is counteracted by the presence of an active-site ligand. Notably, OxDC and OxDC-DSSN at pH 7.2 retain 7 and 15% activity, respectively, which is sufficient to degrade oxalate in a cellular model of primary hyperoxaluria type I, a rare inherited disease caused by excessive endogenous oxalate production. The significance of the data in the light of the possible use of OxDC as biological drug is discussed. © 2019 IUBMB Life, 1-11, 2019.

Identification and Assessment of Drug-User Groups Among Nightlife Attendees: Self-Reports, Breathalyzer-Tests and Oral Fluid Drug Tests.

BACKGROUND AND OBJECTIVES: Even though nightlife studies with potentially intoxicated participants provide the much needed information on drug use, they face additional methodological challenges. This study aimed to explore the utility of such studies by (i) classifying nightlife attendees based on their self-reported drug use and by (ii) examining whether these classifications were meaningful when assessed against other sources of data, including oral fluid drug tests. METHODS: Self-reported questionnaires, oral fluid samples and blood alcohol concentration readings were collected in a sample of 1,085 nightlife patrons recruited outside 12 popular nightclubs in Oslo, Norway, in 2014. Patrons were classified using multiple approaches, including latent class analysis. Group differences were examined by logistic regression models. RESULTS: Participants were classified into 5 mutually exclusive groups: 2 among current non-users ("Never-users"; "Previous users"), 2 among current users ("Multiple drugs"; "Cannabis mainly") and one "Incomplete information" group. Meaningful differences across these groups were observed. For instance, positive tests for any illicit drug were more common in "Multiple drugs" group than in "Cannabis mainly" (62.7 vs. 29.1%, adjusted OR [aOR] 3.77 [2.42-5.84]) or "Incomplete information" groups (62.7 vs. 34.4%, aOR 2.46 [1.26-4.79]). Despite their self-declared non-use, illicit substances were detected in oral fluids of "Never-users" (13.1%; 95% CI 9.9-17.2) and "Previous users" (7.9%; 95% CI 5.1-12.1). CONCLUSIONS: Despite some discrepancies between self-reports and biological tests, self-reports proved both suitable and useful in identification of substantively different drug-user typologies, potentially informing targeted policy responses. Still, methodological challenges associated with onsite studies of illicit drug use should be further explored.

Label-Free Quantification of Anti-TNF-α in Patients Treated with Adalimumab Using an Optical Biosensor.

This study describes the development of an immunosensory label-free quantification methodology based on surface plasmon resonance (SPR) and its applicability in measuring/evaluating therapeutic drug monitoring (TDM) of anti-TNF-α monoclonal antibody (adalimumab) in rheumatoid arthritis (RA) patients. The experimental parameters evaluated in this study were immobilising ligands by pre-concentration assays, sensor surface regeneration, ascertaining the method's sensitivity and correlating the results from quantifying plasma samples by ELISA immunoassay. The results showed that TNF-α quantification values (in RU) were significantly different when comparing patients (~50-250 RU) to controls (~10-20 RU). Likewise, there was 0.97 correlation for patients and 0.91 for healthy volunteers using SPR and ELISA comparison methodologies. SPR immunosensory detection provided a precise, sensitive strategy, along with real-time determination, for quantifying adalimumab, having great potential for clinical routine regarding TDM.

Conformational selection in amyloid-based immunotherapy: Survey of crystal structures of antibody-amyloid complexes.

BACKGROUND: The dominant feature in neurodegenerative diseases is protein aggregations that lead to neuronal loss. Immunotherapies using antibodies or antibody fragments to target the aggregations are a highly perused approach. The molecular mechanisms underlying the amyloid-based immunotherapy are complex. Deciphering the properties of amyloidogenic proteins responsible for these diseases is essential to obtain insights into antibody recognition of the amyloid antigens. SCOPE OF REVIEW: We systematically explore all available crystal structures of antibody-amyloid complexes related to neurodegenerative diseases, including antibodies that recognize the Aß peptide, tau protein, prion protein, alpha-synuclein, huntingtin protein (mHTT), and polyglutamine. MAJOR CONCLUSIONS: We found that antibodies mostly use the conformational selection mechanism to recognize the highly flexible amyloid antigens. In particular, solanezumab bound to Aß12-28 tripeptide motif conformation (F19F20A21), which is shared with the Aß42 fibril. This motif, which is trapped by the antibody, may provide the missing link in amyloid formation. Water molecules often bridge between the antibody and amyloid, contributing to the recognition. GENERAL SIGNIFICANCE: This paper provides the structural basis for antibody recognition of amyloidogenic proteins. The analysis and discussion of known structures are expected to help in the design and optimization of antibodies in neurodegenerative diseases. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.

Application of Tetrameric Recombinant Human Butyrylcholinesterase as a Biopharmaceutical for Amelioration of Symptoms of Acute Organophosphate Poisoning.

We present a procedure for optimizing the expression of recombinant tetrameric butyrylcholinesterase that enables large-scale production with the yield >30 mg/liter (>90 mg/roller bottle). Intravenous injection of the preparation significantly increased survival and decreased the severity of symptoms of poisoning with paraoxon, an organophosphorus toxin.

Quality risk management and data integrity in R&D laboratories supporting CMC lifecycle of biological products.

The development of pharmaceutical products is the critical bridge that moves a potential new medicine from academic discovery to applied treatment of patients. It translates an idea for a new drug to bench-level research on how it can be manufactured, formulated, characterized and controlled for use in non-clinical and early clinical trials. From pre-clinical R&D discovery work through the commercial launch, substantial R&D CMC data is generated to develop and optimize cGMP manufacturing and testing operations, while also supporting product comparability, elucidating product / impurity structures, assessing critical quality attributes, developing the drug delivery mode, and developing the product formulation for long-term stability. Significant R&D CMC work continues post-approval to support continuous improvement and market expansion of the commercial product. These activities are crucial elements of Product Lifecycle Management, and taken together, they comprise Pharmaceutical Quality or Chemistry, Manufacturing and Controls (CMC). The objective of this paper is to mitigate the regulatory ambiguity of R&D quality systems with practical, risk-based examples and recommendations when conducting supportive CMC studies for biological products. Making sound strategic CMC decisions under any circumstances assumes data from R&D studies are reliable, traceable, and complete. While there are specific regulatory guidelines on phase-appropriate cGMP activities, none exist for quality practices in R&D CMC laboratories conducting non-cGMP studies. Hindsight is not the time to discover that R&D studies lack key elements that would otherwise have allowed the data to be directly presented to regulators, if needed. There is a strong prospective business interest in protecting considerable investments made for CMC R&D studies. Therefore, establishment of a robust and stage-appropriate R&D laboratory quality system is essential for companies seeking to capitalize on prior knowledge, protect investments, and be prepared for accelerated approval pathways.

Immunomodulating Enzymes from Streptococcus pyogenes-In Pathogenesis, as Biotechnological Tools, and as Biological Drugs.

Streptococcus pyogenes, or Group A Streptococcus, is an exclusively human pathogen that causes a wide variety of diseases ranging from mild throat and skin infections to severe invasive disease. The pathogenesis of S. pyogenes infection has been extensively studied, but the pathophysiology, especially of the more severe infections, is still somewhat elusive. One key feature of S. pyogenes is the expression of secreted, surface-associated, and intracellular enzymes that directly or indirectly affect both the innate and adaptive host immune systems. Undoubtedly, S. pyogenes is one of the major bacterial sources for immunomodulating enzymes. Major targets for these enzymes are immunoglobulins that are destroyed or modified through proteolysis or glycan hydrolysis. Furthermore, several enzymes degrade components of the complement system and a group of DNAses degrade host DNA in neutrophil extracellular traps. Additional types of enzymes interfere with cellular inflammatory and innate immunity responses. In this review, we attempt to give a broad overview of the functions of these enzymes and their roles in pathogenesis. For those enzymes where experimentally determined structures exist, the structural aspects of the enzymatic activity are further discussed. Lastly, we also discuss the emerging use of some of the enzymes as biotechnological tools as well as biological drugs and vaccines.

Neuropathic pain in axial spondyloarthropathy is underdiagnosed and a confounding factor in biologic drug-switching decision: a cross-sectional study.

OBJECTIVES: The aim of this study was to evaluate the relationship between the presence of neuropathic pain (NeP), disease activity scores and biologic drug-switching decisions in the subjects with axial spondyloarthritis (axSpA) receiving biologic treatment. METHODS: PainDETECT Questionnaire was used to evaluate the presence of NeP in the patients with axSpA aged ≥18 years who had been receiving biologic treatment for at least 6 months. The relationships between disease activity scores, inflammatory markers, life quality index, biologic drug-switching decisions and the presence of NeP were analyzed. RESULTS: A total number of 175 patients with axSpA [ankylosing spondylitis (AS) (n:150) and non-radiographic axSpA (nr-axSpA) (n:25)] were enrolled in the study. NeP was detected in 41.7% of the patients and it was more common in females than in males (p:0.009). PainDETECT scores were positively correlated with disease activity scores, but they were not correlated with inflammatory marker levels. NeP was found to be significantly more common in whom the biologics had been switched 3 or more times (p:0.007). PainDETECT scores were higher and NeP was more prevalent (p:0.028) in the patients for whom drug-switching decisions had been made due to primary or secondary unresponsiveness. CONCLUSION: NeP is more common than estimated in the patients with axSpA and current disease activity scores are insufficient to make a distinction between NeP and inflammatory pain. NeP is a confounding factor in the evaluation of treatment response to biologic agents. In the subjects with AS and nr-axSpA with primary or secondary treatment unresponsiveness, the presence of NeP must be considered before biologic drug-switching decisions. Key Points • Neuropathic pain (NeP) is common in subjects with AxSpA treated with multiple biologic agents. • Current disease activity scores for AxSpA are insufficient to make a differentiation between NeP and inflammatory pain. • NeP is a confounding factor in the evaluation of treatment response to biologic agents. • Patients with AxSpA should be re-evaluated in terms of the presence of neuropathic pain before making biologic drug-switching decisions.

Fractal Kinetic Implementation in Population Pharmacokinetic Modeling.

Compartment modeling is a widely accepted technique in the field of pharmacokinetic analysis. However, conventional compartment modeling is performed under a homogeneity assumption that is not a naturally occurring condition. Since the assumption lacks physiological considerations, the respective modeling approach has been questioned, as novel drugs are increasingly characterized by physiological or physical features. Alternative approaches have focused on fractal kinetics, but evaluations of their application are lacking. Thus, in this study, a simulation was performed to identify desirable fractal-kinetics applications in conventional modeling. Visible changes in the profiles were then investigated. Five cases of finalized population models were collected for implementation. For model diagnosis, the objective function value (OFV), Akaike's information criterion (AIC), and corrected Akaike's information criterion (AICc) were used as performance metrics, and the goodness of fit (GOF), visual predictive check (VPC), and normalized prediction distribution error (NPDE) were used as visual diagnostics. In most cases, model performance was enhanced by the fractal rate, as shown in a simulation study. The necessary parameters of the fractal rate in the model varied and were successfully estimated between 0 and 1. GOF, VPC, and NPDE diagnostics show that models with the fractal rate described the data well and were robust. In the simulation study, the fractal absorption process was, therefore, chosen for testing. In the estimation study, the rate application yielded improved performance and good prediction-observation agreement in early sampling points, and did not cause a large shift in the original estimation results. Thus, the fractal rate yielded explainable parameters by setting only the heterogeneity exponent, which reflects true physiological behavior well. This approach can be expected to provide useful insights in pharmacological decision making.

Two cases with bullous pemphigoid relapsed after using interleukin-17A inhibitors for psoriasis: A paradoxical reaction.

Biological drugs, including IL-17A inhibitors, have become the first-line treating options for moderate to severe psoriasis, and reports show a beneficial effect of IL-17A inhibitors on bullous pemphigoid. Here, we report two cases of bullous pemphigoid in remission that experienced severe flares during treatment with two major IL-17A inhibitors, i.e., ixekizumab or secukinumab for their psoriasis vulgaris. The patient with bullous pemphigoid induced by secukinumab became very recalcitrant to control the relapse. This is by far the first and paradoxical report on the IL-17A inhibitors having a negative effect on bullous pemphigoid patients in previously stable status. Our reports of these two cases alert clinicians to be careful when using IL-17A in pemphigoid patients. We also suggest that patients with psoriasis vulgaris should be asked for a detailed history of pemphigoid and its BP180 autoantibodies status be checked before using these biologicals.

Biological therapies for myasthenia gravis.

INTRODUCTION: Recently, treatments for myasthenia gravis (MG) have progressed significantly. Symptoms of some patients with refractory MG are not relieved by conventional therapies, and such patients might benefit from novel biological treatments that are being developed. AREAS COVERED: We review several novel biological therapies for MG, such as complement inhibitors, neonatal Fc receptor inhibitors, anti-B cell drugs, and IL-6 receptor inhibitors. We also report the modes of action, efficacy, safety, and tolerability of these drugs. EXPERT OPINION: Several biological therapies have been developed for MG, and these biologics are promising agents for treating refractory MG. Establishing biomarkers and accumulating evidence of therapeutic response is required to provide the most appropriate biological treatment for each patient.

Pharmacognostic evaluation of Artemisia maritima L. a highly medicinal specie of genus Artemisia.

The light and scanning electron microscopic observations were carried out for anatomical features of leaf, pollens and powder.Microscopic studies provide useful information for identification and authentication of adulteration in A. maritima. Nutritional analysis of A. maritima revealed that life fundamental macromolecules such as carbohydrates (49.63 %) crude proteins (13.17 %) and crude fibers (21.06 %) were present in sufficient quantity while crude fats (4.11 %) reported in low quantity. The life essential elements such as Mg (9.472 ± 0.011), Ca (4.152 ± 0.135) and Fe (4.112 ± 0.002) were found in high concentration while heavy metals reported under the safety threshold of WHO. These observations favored A. maritima an alternative of food.Appreciable quantity of phenolics (17.64 ± 0.574) and flavonoids (7.67 ± 0.069) were found while qualitatively active phytochemicals were reported. The FTIR characterization of A. maritima crude powder revealed chromatogram in 3328.61 to 408.68 frequency range and 24 characteristic peaks on the basis of which different compounds of biological importance were classified. HPLC-UV technique quantifiedand identified six phenolic compounds morin,epigallocatechin gallate, catechin hydrate,ellagic acid, pyrogallol andrutin. Identification of compounds through GC-MS chromatogram revealed the presence of 46 compounds in methanolic fraction however 17 compounds of biological importance were selected. In-vitro biological evaluation of A. maritima for antioxidant, antimicrobial, antidiabetic (12.61 ± 0.113 %) and cytotoxic activities (LC50 = 20 µg/ml) suggested that methanolic fractions exhibited the highest activity as compared to chloroform and ethyl acetate fractions. The MIC values of 10 or 15 mg/ml were recorded for most of the fungal pathogens. Antibacterial activity revealed 3.75 mg/ml of MIC values against B. subtilis and 1.87 mg/ml against S. aureus, E. coli and P. aeruginosa. In-vivo biological evaluation revealed thatmaximum inhibition was observed for crude extract at 250 mg/kg body weight. The mechanism underlined in-vivo analgesic responses was carried out which revealed that naloxone (morphine and tramadol antagonist) showed no prominent effect while Glibenclamide pretreatment minutely modified the analgesic action. These observations clearly indicted the absence of opiod receptors and involvement of ATP sensitive potassium channels.

Recalcitrant Ulcerative Pyoderma Gangrenosum of the Leg Responsive to Tildrakizumab: A Case Report.

Elevated levels of inflammatory mediators-including the interleukin IL-23-are implicated in the pathogenesis of pyoderma gangrenosum (PG), an autoinflammatory neutrophilic dermatosis characterized by rapidly enlarging, suppurative ulcers and cribriform scarring. Here, we present the first case report of significant response of isolated ulcerative PG with tildrakizumab, a biologic agent directed against the p19 subunit of IL-23, in an elderly woman with extensive treatment-refractory PG on her left leg. Tildrakizumab (100 mg subcutaneously at weeks 0 and 4, then every 8 weeks, and eventually increased in frequency to every 6 weeks), combined with acetic acid soaks each morning and chemical debridement every evening with 3% hydrogen peroxide, resulted in progressive decrease in ulcer size and depth, re-epithelialization, and recovery of sensory perception. This report describes the dramatic clinical response of ulcerative PG on the leg with tildrakizumab.

Vedolizumab for the Management of Refractory Behçet's Disease: From a Case Report to New Pieces of Mosaic in a Complex Disease.

Objectives: When treating Behçet's disease (BD), anti-tumor necrosis factor (TNF)-α agents have become a second-line therapy when conventional immunosuppressive drugs have failed. However, in the case of failure of treatment with anti-TNFα drugs, further options are limited. Based on previous reports of the efficacy of vedolizumab (VDZ) in inflammatory bowel diseases, we decided to administer VDZ to treat a patient with intestinal BD. Methods: We present the case of a 49-year-old female patient with BD. Her clinical manifestations included erythema nodosum, oro-genital ulcers, positive Pathergy test, positive HLA-B51, and biopsy-proven intestinal BD. The patient was unsuccessfully treated with conventional immunosuppressive and several biological agents. Results: Treatment with VDZ was started intravenously at a dose of 300 mg at 0, 2, and 6 weeks and then every 4 weeks. After the second dose of VDZ, the patient reported a marked improvement of intestinal BD and a concomitant amelioration of arthralgia, erythema nodosum lesions and aphthosis. Clinical remission was achieved at 6 months after starting VDZ. Conclusion: VDZ might represent a valid option to treat patients with BD who are non-responsive to standard treatments or anti-TNFα agents, particularly, those cases with intestinal involvement.

Preference for Telemedicine Versus In-Person Visit Among Patients with Psoriasis Receiving Biological Drugs.

INTRODUCTION: The use of telemedicine has significantly increased since the outbreak of the SARS-CoV-2 pandemic. In the dermatological setting, patients with stable plaque psoriasis on maintenance therapy with biological drugs may be suitable candidates for telemedicine, although their preference for telemedicine has not yet been investigated. The aim of this study was to investigate the preference for telemedicine versus in-person visit among patients with psoriasis receiving biological drugs and the reported reasons behind their preferences. METHODS: Consecutive adult patients with chronic plaque psoriasis in stable clinical remission (Psoriasis Area Severity Index [PASI] ≤ 3 for at least 12 months) receiving maintenance biological therapy answered a survey investigating whether they would choose telemedicine or in-person visit for the next scheduled visit and the reasons behind their preference. The survey was undertaken through a questionnaire that was developed according to a structured process. RESULTS: Of the 246 participants in the survey, 118 (48%) preferred telemedicine over an in-person visit for their next scheduled visit with a dermatologist. Multivariate logistic regression analysis revealed that previous experience with digital video-communication tools was a significant predictor for the preference for telemedicine (odds ratio [OR] 10.75; 95% confidence interval [CI] 3.61-32.03), while older age (< 60 years) was negatively associated with the preference for telemedicine (OR 0.30; 95% CI 0.10-0.90). The most common reasons (75%) for preferring telemedicine were saving time and safety in relation to the risk presented by the Sars-CoV-2 pandemic (38%). In contrast, 56% of the patients who preferred the in-person visit option declared that they were unable to use video-communication tools. CONCLUSION: About half of the patients with stable psoriasis receiving biological drugs may be good candidates for telemedicine.