Safety Of Biologic Therapy Research Articles

Principles of modern diagnosis and treatment of atopic dermatitis and bronchial asthma: Clinical case

This article presents the experience of successful use of the drug dupilumab in a patient with severe atopic dermatitis and bronchial asthma. The effectiveness of biological therapy with dupilumab 300 mg subcutaneously for 52 weeks of T-2 associated diseases, including a combination of severe atopic dermatitis and bronchial asthma, uncontrolled course based on the case history of patient Ts., born in 2006 with the diagnosis "Main: atopic dermatitis, common form, severe course. Concomitant diagnosis: bronchial asthma, persistent course, uncontrolled, moderate severity". Dynamic monitoring of the total blood count with the calculation of the absolute number of eosinophils in peripheral blood was performed. The study showed high efficacy and safety of biological therapy with dupilumab 300 mg subcutaneously every 2 weeks for 52 weeks with a combination of severe atopic dermatitis and bronchial asthma, uncontrolled course in patient Ts (Born in 2006). The examination of the ALEX2 allergochip made it possible to establish the molecular components of the primary causal allergens, predict the course of an allergic disease, and carry out successful elimination measures against food allergens, preserving the maximum set of nutrients in the patient's diet. Dupilumab therapy in severe atopic dermatitis and uncontrolled bronchial asthma leads to clinically significant improvement in the course of diseases, control of disease symptoms. Atopic dermatitis shows a decrease in itching of the skin, normalization of sleep, improvement of quality of life. With bronchial asthma, a reduction in exacerbations, normalization of respiratory function indicators, complete control of the disease has been achieved. The targeted biological drug dupilumab has a targeted effect on the key links in the pathogenesis of atopic dermatitis and bronchial asthma and reduces the burden of severe diseases. Therefore, the use of dupilumab in atopic dermatitis and bronchial asthma contributes to achieving disease control and improving the patient's quality of life.

Biologic Therapy for Moderate to Severe Psoriasis. Real-World Follow-up of Patients Who Initiated Biologic Therapy at Least 10Years Ago.

IntroductionThe aim of this study was to evaluate response and drug survival of biologic therapy in patients with moderate to severe plaque-type psoriasis who initiated biologic therapy at least 10 years ago, in a real-world setting.MethodsThis was an observational retrospective follow-up study that included patients with moderate to severe plaque-type psoriasis who initiated biologic therapy between October 2006 and December 2009. Efficacy was expressed as the percentage of patients achieving a 50, 75 and 90% reduction from baseline in the Psoriasis Area and Severity Index (PASI 50, PASI 75, PASI 90, respectively) every 3 months during the first year of therapy and then every 12 months up to the end of follow-up or withdrawal from the study.ResultsA total of 56 patients were included in the study, representing 140 treatment lines (median 2, range 1–8); of these patients, 53 were still receiving biologic therapy at the end of the study. The mean duration of biologic therapy was 140.4 (range 47.6–175.4) months. Etanercept was used in 98.2% of patients, followed by efalizumab (42.9%), adalimumab (41.1%), ustekinumab (33.9%) and infliximab (16.1%). Treatment lines were switched in 62.1% of treatments: 24.3% due to secondary failure, 20.7% due to primary failure and 3.6% due to side effects. No patient treated with anti-interleukins had to discontinue treatment due to side effects. Ustekinumab had the highest drug survival.ConclusionsThis study in the real-world-setting shows maintenance of long-term efficacy and safety of biologic therapy in patients with moderate to severe plaque psoriasis in daily practice who initiated biologic therapy 10 years ago.

A143 SAFETY OF BIOLOGICAL THERAPIES IN ELDERLY IBD: A SYSTEMATIC REVIEW

BackgroundThere was a significant progress in the medical therapy of inflammatory bowel disease(IBD) with the advent of biological compounds, yet patients may experience adverse events(AE): infusion reactions, serious infections and malignancies, understudied in vulnerable patient populations (e.g. elderly).AimsOur aim was to perform a systematic review to assess the safety of the biologic therapies in the elderly IBD population.MethodsMedline databases and conferences proceedings were searched between January 1, 2010, and June 1, 2021. Two reviewers independently evaluated the collected studies based on inclusion and exclusion criteria. Search was focused on IBD/CD/UC, any biological therapy, and adverse events in the elderly. The methodological quality of the included studies was assessed using the Newcastle– Ottawa Scale (NOS). This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA).ResultsOur search identified 2885 articles and 12 congress abstracts trough the data base search, finally 14 peer reviewed papers and 3 abstracts met the inclusion criteria. The majority of the studies were retrospective, merging IBD patients, with an age limit of 60 or 65 years for elderly, from Europe or North America. The gender ratio was equal except in the USA veteran database. The identified studies collected safety data on anti-TNF therapy, vedolizumab and ustekinumab. We selected studies with at least 1 year follow-up period. Ranges of AE rates(infliximab/adalimumab 6–39/100patient-years (PY), vedolizumab 6–26/100 PY and ustekinumab 6–18.2/100 PY), infection rates (anti TNF 2.5–31/100PY, vedolizumab 2.6–77/100 PY and ustekinumab 5.2–35.7/100 PY) or infusion/injection reactions (anti TNF 0–14/100PY, vedolizumab 0.9–5/100 PY and ustekinumab 0–2.6/100 PY), were not different among the biological medication.ConclusionsWe report for the first time the comparative safety of biological therapies in elderly IBD patients. Ranges of adverse events or infections were wide but not different among the medications. Current data are insufficient to suggest prioritizing among biologicals in the elderly based on the safety, larger studies in elderly IBD patients are warranted.Funding AgenciesNone

P318 Safety of Biological Therapies in Elderly IBD: a Systematic Review and Meta-analysis

Abstract Background There was a significant progress in the medical therapy of inflammatory bowel diseases(IBD) with the advent of biological compounds, yet patients may experience adverse events(AE): infusion/injection reactions, infections and malignancies, understudied in vulnerable patient populations (e.g. elderly). Methods We systematically searched PubMed/Medline and conferences proceedings between January, 1, 2010, and June, 1, 2021, to identify eligible studies that examined the safety of biologic therapies in elderly patients with IBD. Two reviewers independently evaluated the collected studies based on inclusion and exclusion criteria. Search was focused on MESH Terms including IBD/CD/UC, biological therapy, adverse events, infections, infusion/injection reaction and malignancy and elderly. Results Our search identified, 2885 articles and, 12 congress abstracts trough the data base search, finally, 14 peer reviewed papers and, 3 abstracts met the inclusion criteria. Most studies were retrospective, merging CD and UC patients, with an age limit of, 60 or, 65 years for elderly, from Europe or North America. According to our meta-analysis the rates of AE were not different according to the type of biologics (mean rate:, 11.3 (CI, 95%, 9.9–12.7)/100 pts years; p=0.11) in elderly IBD patients with the use of anti-TNF, vedolizumab(VDZ) and ustekinumab(UST). Similarly, rates of infection (mean rate:, 9.5 (CI, 95%, 8.4–10.6)/100 pts years; p=0.56). On the other hand, regarding infusion/injection rates were more common in patients on anti-TNFs (mean rate:, 2.51 (CI, 95%, 1.7–3.4/100 pts years; p=0.02) and malignancy rates were higher in elderly patients on VDZ/UST (mean rate:, 2.14 (CI, 95%, 1.6–2.8)/100 pts years; p=0.01). Two studies directly comparing anti-TNF and VDZ reported similar efficacy and safety in the elderly IBD population. (p=0.56; Total: reflects patient year of follow-up.) Conclusion We report the first meta-analysis on the comparative safety of biological therapies in elderly IBD patients. Rates of adverse events and infections were not different across the biologics. In contrast, infusion/injection reactions were more common in patients on anti-TNFs. Current data are insufficient to suggest sequencing among biologicals in the elderly based on the safety, larger studies in elderly IBD population are warranted.

Safety of biological therapy in children and adolescents with severe asthma during the COVID-19 pandemic: a case series.

Background and aim:It is still unclear whether patients with severe asthma are at greater risk of developing severe COVID-19, particularly pediatric allergic patients under biologic therapy. Studies targeting pediatric patients are currently limited; thus, this study aims to assess the clinical characteristics of young patients with severe asthma under biological therapies during the COVID-19 pandemic.Methods:We collected data from February 2020 to April 2021. Patients with severe asthma treated with biological therapies (omalizumab and mepolizumab) have been enrolled. We described demographic data, clinical features, therapies, comorbidities, and laboratory findings for each patient. For patients who got COVID-19, we also described the severity of the disease, the need for hospitalization, and specific therapy.Results:A total of 14 patients were included in the study, 11 (78.6%) of them under treatment with omalizumab and 3 (21.6%) with mepolizumab. We identified four patients (28.6%) who tested positive for SARS-CoV-2. Two patients treated with mepolizumab had an asymptomatic disease, and two patients treated with omalizumab had mild disease. Only one patient with mild COVID-19 required hospitalization and specific therapy because of severe obesity.Conclusions:No differences regarding the SARS-CoV-2 infection have been found between the two treatments groups. Furthermore, any poor outcome has been observed, confirming the safety of biological therapies. The limited number of patients enrolled and the lack of a control group did not establish a significant risk for infections for these patients. (www.actabiomedica.it).

Fertility and pregnancy outcomes in patients with immune-mediated rheumatic diseases

Impaired fertility is an important public health concern, especially in patients with immune-mediated rheumatic conditions. Frequency of infertility /subfertility vary among rheumatic diseases – higher in systemic lupus erythematosus or rheumatoid arthritis, than in other autoimmune diseases. Risk factors like age, nulliparity, disease activity or medication such as NSAIDs, corticosteroids, cyclophosphamide are mostly encountered. Treating a pregnant woman is a challenge: the well-being of mother and child has to be considered, as tight disease control before, during pregnancy and postpartum is mandatory to minimize adverse outcome risk. Safety of biological therapies during preconception, pregnancy, and postpartum is crucial, anti-TNFs being safe in early pregnancy, second, but not third trimester. Etanercept and certolizumab may be considered for use throughout pregnancy due to low rate of transplacental passage. Concerning the child, live-attenuated vaccines are to be avoided for the first 6 months of life due to persistence of biologics.

Safety of biological therapy in elderly patients with severe asthma

Objective To assess the safety of biological therapy for severe T2 asthma (omalizumab, mepolizumab, benralizumab and reslizumab) under real-life conditions in elderly patients older than 70 years. Methods Retrospective data collection including clinical characteristics, comorbidities, treatment, disease control and adverse events (AE) of all patients with severe asthma on biological therapy older than 70 years seen in the Severe Asthma Unit of our hospital. Results Of 147 patients with severe asthma being treated with biologics, 21 patients older than 70 years were included. The median age of these patients was 76.3 years (range 71–86) and the majority were women (n = 18, 85.7%). There were 9 patients (42.9%) who experienced an AE related to biological treatment. Four (44.4%) were in treatment with omalizumab, two (22.2%) with mepolizumab, two patients (22.2%) with reslizumab and one (11.1%) with benralizumab. The median FEV1 (%) was 66%. These patients had a considerably higher body mass index (BMI). No significant differences were found for any other variable. Most of the AE reported were considered mild with the exception of one case of systemic AE (anaphylaxis) associated with omalizumab. Conclusion This study indicates that the prescription of biological therapy in elderly patients with severe asthma seems to be safe. More evidence is needed in this particular population.

Immunological Targets of Biologic Drugs in Allergic Skin Diseases in Children.

Atopic dermatitis and urticaria are two invalidating skin disorders that are very common in children. Recent advances in the understanding of their specific intracellular molecular pathways have permitted the development of precise biological molecules, targeting inflammatory mediators and arresting the pathogenetic pathways of skin diseases. Many biologics with promising results have been studied, although few are currently approved in children. In this review, we aim to provide the latest evidence about the use, indications, efficacy and safety of biologic therapies to treat atopic dermatitis and chronic urticaria in children and adolescents.

Comparative efficacy and safety of biologic therapies for moderate-to-severe Crohn's disease: a systematic review and network meta-analysis

Data are needed to inform the positioning of biologic therapy in the treatment of moderate-to-severe Crohn's disease, both first line and after previous biologic exposure. We aimed to assess the comparative efficacy and safety of biologics in patients with Crohn's disease. We did a systematic review and network meta-analysis of phase 2 and phase 3 randomised controlled trials done in adults (≥18 years) with moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220-450) treated with tumour necrosis factor (TNF) antagonists, anti-integrin, anti-interleukin (IL)-12 and IL-23p40, or anti-IL23p19 agents, either alone or in combination with immunosuppressants, as their first-line biologic or after previous biologic exposure, compared with placebo or an active comparator. The minimum duration of therapy was 14 days for trials reporting induction of remission in active disease and 22 weeks in trials reporting maintenance of remission. We searched Medline, EMBASE, the Cochrane CENTRAL Register of Controlled Trials, conference proceedings, trial registries, and unpublished data from inception to June 3, 2021, without any language restrictions. Summary estimates of the primary and secondary outcomes were extracted from the published reports; individual patient-level data were not sought. The primary endpoint was induction of clinical remission in patients with active disease (CDAI <150) and maintenance of remission in patients with response to induction therapy, with data extracted from published reports. A network meta-analysis with multivariate consistency model random-effects meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values. The search strategy yielded 18 382 citations, of which 31 trials were eligible for inclusion. On the basis of 15 randomised controlled trials including 2931 biologic-naive patients, infliximab monotherapy (odds ratio [OR] 4·53 [95% CI 1·49-13·79]), infliximab combined with azathioprine (7·49 [2·04-27·49]), adalimumab (3·01 [1·25-7·27]), and ustekinumab (2·63 [1·10-6·28]) were associated with significantly higher odds of inducing remission compared to certolizumab pegol (all moderate confidence); infliximab and azathioprine combination therapy was also associated with significantly higher odds of inducing remission than vedolizumab (3·76 [1·01-14·03]; low confidence). On the basis of ten randomised controlled trials including 2479 patients with previous biologic exposure, adalimumab after loss of response to infliximab (OR 2·82 [95% CI 1·20-6·62]; low confidence), and risankizumab (2·10 [1·12-3·92]; moderate confidence), were associated with higher odds of inducing remission than vedolizumab. No differences between active interventions were observed in maintenance trials. Most trials were at low or uncertain risk of bias. Although biologic treatment choices in patients with moderate-to-severe Crohn's disease must be individualised for each patient, this analysis suggests that either infliximab with azathioprine or adalimumab might be preferred as a first-line therapy, and adalimumab (after infliximab loss of response) or risankizumab might be preferred as a second-line therapy, for induction of clinical remission. None.

Efficacy and safety of biological drugs in interstitial lung disease associated with connective tissue diseases

ABSTRACT Introduction Interstitial lung disease (ILD) is one of the most important manifestations of connective tissue diseases (CTD) due to its association with high morbidity and mortality. Areas covered Literature review focused on the evidence on efficacy and safety of biological therapy. Expert opinion Rituximab (RTX) is the most studied drug, though tocilizumab (TCZ) has methodologically more robust evidence, whereas abatacept (ABA) has only anecdotal reports. RTX studies suggest a clinically relevant effect on lung function and fibrosis in refractory to conventional treatment patients, with a good safety profile. Its multi-level efficacy in systemic sclerosis and the potentially more favorable response of anti-synthetase syndrome, especially when administered early in acute-onset or exacerbated ILD stand out over current standard of care, pending the availability of randomized controlled clinical trials. The significant and clinically meaningful benefit found in lung function and fibrosis with TCZ in faSScinate and focuSSced trials represents a change with respect to the usual practice, reinforcing the importance of treatment in early subclinical or clinical SSc-ILD patients with risk factors for ILD progression. This evidence has led to the inclusion of both RTX and TCZ in the expert-based therapeutic algorithms or recommendations for CTD-ILD management.

Biological Therapy in Noninfectious Pediatric Uveitis: A Systematic Review.

PurposeNoninfectious pediatric uveitis is a potentially blinding disease often associated with systemic conditions. In cases of chronic anterior uveitis without adequate response to steroids and immunosuppressants, biological response modifiers would be viable therapeutic options. Still, evidence is lacking on the safety of the long-term use of these drugs in children. Therefore, this study aimed to evaluate the efficacy and safety of biological therapy to treat noninfectious pediatric uveitis.MethodsA systematic review was performed to identify original studies involving biological therapy for children diagnosed with noninfectious uveitis. Quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) classification system.ResultsNine studies involving 526 children were eligible. Adalimumab was superior to placebo in reducing inflammatory activity (risk ratio (RR) 3.21 [95% confidence interval (CI) 1.65–6.27]; P = 0.0006; I2 = 0%) and steroid use (RR 2.27 [95% CI 1.03–4.99]; P = 0.04; I2 = 0%, low-certainty evidence). There was no difference between adalimumab and placebo in the occurrence of systemic adverse events (RR 2.51 [95% CI 0.74–8.54]; P = 0.14; I2 = 48%) and local events (RR 1.15 [95% CI 0.46–2.88]; P= 0.76; I2 = 1%). There was no difference between adalimumab and infliximab in response to treatment (RR 1.18 [95% CI 0.69–2.03]; P= 0.55; I2 = 91%, very low-certainty evidence) and in the occurrence of adverse effects (RR 0.84 [95% CI 0.41–1.73]; P= 0.64; I2 = 18%, low-certainty evidence).ConclusionThere is low to very-low evidence that biological therapy is effective and safe in managing noninfectious pediatric uveitis. Future large randomized trials may provide more substantial evidence to confirm these results.

New possibilities of therapy of T2-associated diseases

New opportunities for the treatment of T2-associated diseases in recent years, the number of patients with atopic dermatitis (ATD), having a moderate and severe form of course, has been increasing. According to research, 30% of the world's population suffer from allergic diseases, such as bronchial asthma (BA), ATD, food allergies, anaphylaxis, chronic polypous rhinosinusitis. The development of these diseases is based on the pathophysiological mechanism of T2-mediated immune inflammation, where cytokines IL-4 and IL-13 play a key role. Diseases based on this type of inflammation belong to the group of T2-associated diseases. Thanks to targeted therapy with dupilumab, which affects the main links of pathogenesis, it is possible to effectively cope with the main manifestations of severe and moderate ATD and BA.&#x0D; Aim. To evaluate the effectiveness of biological therapy with dupilumab 300 mg subcutaneously for 52 weeks of T2-associated diseases, including a combination of severe ATD and BA, uncontrolled course in a teenager C. (born 2006).&#x0D; Materials and methods. The analysis of the medical history of the patient C., born in 2006, who received therapy with dupilumab 300 mg subcutaneously every 2 weeks for 52 weeks with the diagnosis Main: ATD, common form, severe course. Secondary diagnosis: BA, persistent course, uncontrolled, moderate severity. Dynamic monitoring of the total blood count with the calculation of the absolute number of eosinophils in peripheral blood was performed. The allergological examination included the determination of specific IgE-AT to 300 allergens using ALEX2 technology. Criteria for the effectiveness of ATD therapy were evaluated on the SCORAD scale in dynamics, an AST test was used for BA, as well as a study of the function of external respiration before treatment and during therapy.&#x0D; Results. The study showed high efficacy and safety of biological therapy with dupilumab 300 mg subcutaneously every 2 weeks for 52 weeks of T2-associated diseases, including a combination of severe ATD and BA, uncontrolled course in patient C. (born in 2006). The conducted allergological examination with the help of the ALEX2 Allergochip made it possible to establish the molecular components of the primary causal allergens, predict the course of an allergic disease, and carry out successful elimination measures against food allergens, preserving the maximum set of nutrients in the patient's diet.&#x0D; Conclusion. Therapy with dupilumab 300 mg subcutaneously every 2 weeks for 52 weeks of T2-associated diseases, with manifestations of severe ATD and BA, uncontrolled course leads to clinically significant improvement in the course of diseases, control of symptoms of diseases. ATD shows a decrease in itching of the skin, normalization of sleep, improvement of quality of life. With BA, a significant reduction in exacerbations, normalization of respiratory function indicators, complete control of the disease has been achieved. The targeted biological drug dupilumab has a targeted effect on the key links in the pathogenesis of ATD and BA and reduces the burden of severe diseases. Therefore, the use of dupilumab in ATD and BA contributes to achieving disease control and improving the patient's quality of life.

Biologic Therapy and Severe Asthma in Children.

Severe asthma is a heterogeneous, complex and chronic disease widespread in the pediatric population. According to the recent findings about the different endotypes of asthma in children, each one characterized by specific intracellular molecular pathways, several innovative biologic therapies have been developed. Due to their precise ability to target specific inflammatory type 2 mediators, biologics have revolutionized the care of chronic allergic diseases in the pediatric and adult population. In this review, we aim to provide the latest evidence about the use, indications, efficacy and safety of biologic therapies to treat severe asthma in children and adolescents.

Safety and Efficacy of Biological Therapy in Chronic Antibiotic Refractory Pouchitis: A Systematic Review With Meta-analysis.

Pouchitis is the most common long-term complication after ileal pouch-anal anastomosis in patients with ulcerative colitis. Those with ≥3 episodes of pouchitis/year and symptoms despite antibiotics are considered to have chronic antibiotic refractory pouchitis (CARP). While several agents including probiotics, steroids and immunomodulators have been used, treatment of CARP remains challenging. We conducted a systematic review and meta-analysis evaluating the safety and efficacy of various biological agents in treatment of CARP. Multiple databases were searched through June 2020 for studies that reported the efficacy and safety of biological therapy including antitumor necrosis factor-alpha agents [infliximab (IFX) and adalimumab (ADA)], vedolizumab (VDZ), and ustekinumab in CARP. We excluded studies on Crohn's like and/or other inflammatory complications of the pouch. Meta-analysis was performed to calculate pooled rates of clinical as well as endoscopic improvement and remission. We included 15 studies with 311 patients in our final analysis. Ninety-two patients were treated with IFX, 42 with ADA, 144 with VDZ and 33 with ustekinumab. Pooled rate of clinical improvement was 71.4%, 58.2%, 47.9% and clinical remission was 65.7%, 31%, 47.4% with IFX, ADA, and VDZ, respectively. Pooled rate of endoscopic improvement was achieved in 61.2% patients treated with VDZ while endoscopic remission was achieved in 70.3% patients treated with IFX. Adverse events were reported in 3.9% patients. Biologic therapy is safe and effective in the treatment of CARP.

P338 effectiveness and safety of biological therapies in elderly inflammatory bowel diseases patients results from a multi center study of Geteccu

Abstract Background Biological drugs are being increasingly used for the treatment of inflammatory bowel diseases (IBD) in elderly patients. Despite the particular characteristics of this population subgroup, the efficacy and safety of these treatments in real clinical practice is poorly evaluated. Methods Retrospective and multicenter study of GETECCU, carried out in 28 Spanish hospitals. Patients with IBD who started biological treatment (Infliximab, Adalimumab, Golimumab, Ustekinumab or Vedolizumab) aged 65 years or older were included. Efficacy (clinical- at the criteria of the responsible physician-, biochemical and endoscopic) was assessed at 12-14 weeks and at 52 weeks of treatment. Adverse effects such as tumors or serious infections were also recorded. Results A total of 570 patients were included, baseline characteristics are shown in Table 1. Biologics used were: Infliximab (214, 37.5%), Adalimumab (167, 29.3%), Golimumab (16, 2.8%), Ustekinumab (73, 12.8%) and Vedolizumab (100, 17.5%). After 12-14 weeks of treatment, in 38.7% (220) of the cases clinical remission had been achieved and in 47.7% (270) there was clinical response without remission. However, 80 patients (13.9%) had no response, resulting in treatment discontinuation due to primary failure. At week 52, only 379 patients (66.5%) continued on biological treatment: 216 (57%) were in clinical remission (216, 57.0%) while 129 (34%) had response without remission and 34 (9%)had no response. In addition, 119 patients (21%) had an endoscopic study performed: 47 (39,5%) presented with endoscopic remission, 38 (31,9%) with mild activity, 28 (23,5%) with moderate activity and 6, (5.1%) with severe activity. At the end of the follow-up, only 60% of the patients continued on biological treatment, being the reason for withdraw lack of efficacy or due to the report of adverse side effects. Regarding treatment safety in this population, 12.1% (68 patients) suffered an infectious complication with a microbiological diagnosis, requiring hospitalization in 62.1% of the cases. In addition, 39 patients (6.9%) were diagnosed with a tumor until the end of the follow-up, noting that 34.2% of the cases continued on biological therapy after the diagnosis. Likewise, in 25 patients (36.8%) this infection forced discontinuation of biological treatment. Finally, 10 patients stopped biological treatment due to a serious adverse reaction to it Conclusion Response rates to biological treatment in elderly patients are similar to those described in the general population, with approximately one third of failures happening during the first year. However, a remarkable proportion of patients developed a serious adverse effect that could be related to treatment

COMPARATIVE EFFECTIVENESS AND SAFETY OF VEDOLIZUMAB AND ANTI-TUMOR NECROSIS FACTOR AGENTS IN OLDER ADULTS WITH INFLAMMATORY BOWEL DISEASES IN MEDICARE ADMINISTRATIVE CLAIMS DATABASE

The number of older adults with inflammatory bowel diseases (IBD) is increasing. Older adults with IBD are less likely to receive effective immunosuppression. We aimed to determine efficacy and safety of biologic therapies in older adults with IBD.

COMPARATIVE EFFECTIVENESS AND SAFETY OF VEDOLIZUMAB AND ANTI-TUMOR NECROSIS FACTOR AGENTS IN OLDER ADULTS WITH INFLAMMATORY BOWEL DISEASES IN MEDICARE ADMINISTRATIVE CLAIMS DATABASE

Abstract Background The number of older adults with inflammatory bowel diseases (IBD) is increasing. Older adults with IBD are less likely to receive effective immunosuppression. We aimed to determine efficacy and safety of biologic therapies in older adults with IBD. Methods We conducted a retrospective cohort study using an active comparator, new user design in a 20% random sample from the 50 state Medicare claims database between May 2014 and December 2018. We included patients who initiated vedolizumab or an anti-tumor necrosis factor (TNF)-α agent (infliximab, adalimumab, golimumab or certolizumab) following 12-months of continuous enrollment in Medicare fee-for-service Parts A/B/D without either study drug. Patients were required to be ≥65 years old and have ≥2 international classification of disease (ICD) codes of Crohn’s disease (CD) or ulcerative colitis (UC). We excluded patients who received other biologic therapies and/or those who had ≥2 codes for other immunologic conditions. Pertinent co-variates included were age, sex, race Charlson Co-morbidity Index (CCI), predicted probability of frailty, healthcare utilization and baseline IBD medications. The outcomes of interest were hospitalizations, IBD-related surgery and new corticosteroid use ≥ 60 days after drug initiation. We described the study population, assessed health care utilization and use of other IBD medications. We estimated crude incidence rates and hazard ratios (HR) adjusted for the covariates using standardized mortality ratio (SMR) weights. Results We identified 488 vedolizumab users and 2,213 anti-TNF users. The median age was 72 years in the vedolizumab cohort and 71 years in the anti-TNF cohort; 12% of both cohorts were aged ≥80 years. Differences in the two cohorts existed with regards to sex, race, baseline healthcare utilization and IBD-related medications, but all the baseline differences were balanced by weighting measured by a standardized mean difference (SMD) &amp;lt;0.1 (Table 1). After weighting, vedolizumab users were less likely to be hospitalized in the 12 months after biologic initiation (HR: 0.81, 95% CI: 0.68 – 0.96). While there was no significant difference in IBD related hospitalizations, older adults with IBD were less likely to have an infection-related hospitalization (HR: 0.39, 95% CI: 0.23 – 0.65). There were no significant differences in IBD related surgery and steroid use after induction (Table 2). Conclusions In this large, retrospective cohort study of older IBD patients who were new users of vedolizumab and anti-TNF agents, we found that older patients initiated on vedolizumab were significantly less likely to have an infection-related hospitalization. However, there were no significant differences in IBD-related hospitalizations, IBD-related surgery or corticosteroid use after biologic induction.

Safety of Biological Therapy in Children With Inflammatory Bowel Disease.

Retrospective, observational, single-center, cohort study investigating the safety profile of biological therapy in children with inflammatory bowel disease (IBD). Retrospective, observational, cohort study of pediatric patients with IBD, receiving infliximab, adalimumab, vedolizumab, or ustekinumab for at least 2 months. Data related to the immediate and delayed adverse events (AEs) were collected, focusing on the reaction type and severity, the time of onset, the outcome and the temporary or definitive therapy discontinuation secondary to the AE. Number of suspected and confirmed coronavirus disease-209 (COVID-19) cases and their outcomes, as well as flu vaccination coverage were collected. One hundred eighty-five children were included (101 [55%] CD, 82 [44%] UC, and 2 [1%] IBDU): 149 received infliximab (IFX) (81%), 88 (48%) adalimumab (ADA), 18 (21%) vedolizumab, and 4 (2%) ustekinumab. The overall AE rates were 49%, 67% of whom likely medication-related. Eleven (6%) patients experienced more than 1 AE, 18 patients (10%) presented an immediate reaction, and 82 (45%) a delayed AE. Among the 90 patients experiencing at least 1 AE, 97% had mild-to-moderate AEs. Only 4 SAEs were reported (4%). Treatment discontinuation because of AE occurred in 25 patients (14%). Four COVID-19 cases were reported, all with a mild course. Our findings confirm a good safety profile of biologics. Infusion reactions to IFX administration remain one of the main issues, significantly linked to its immunogenicity and consequently with an impact on its efficacy and durability.

Medication adherence and persistence of psoriatic arthritis patients treated with biological therapy in a specialty pharmacy in Brazil: a prospective observational study

Background:Pharmaceutical services in Brazil provide access, supply, and rational use of drugs for all population and an effort has been made to improve the quality of these services. Biological drugs are high-cost drugs supplied in Brazil that can inhibit disease progression and improve the quality of life of psoriatic arthritis (PsA) patients. However, some patients did not achieve therapeutic goals.Objective:To evaluate the medication adherence and persistence of PsA patients treated with tumor necrosis factor inhibitors (anti-TNF) drugs and their associated factors.Methods:A prospective observational study was performed at a single-specialty pharmacy in Belo Horizonte, Brazil. Medication adherence, persistence, and clinical outcomes were evaluated at 12 months of follow-up. Medication persistence was historically compared to overall PsA patients treated in Brazil. Associated factors were identified through log-binomial regression.Results:One hundred ninety-seven PsA patients were included in the study, of whom 147 (74.6%) and 142 (72.1%) had medication adherence and persistence, respectively. Patients treated with infliximab presented the highest adherence (90.5%) and persistence rate (95.2%) in comparison to patients treated with other drugs, except for adalimumab versus infliximab for adherence outcome. All clinical measures significantly improved in patients with medication adherence and persistence. Medication persistence was higher for patients attended by specialty pharmacy than other PsA patients in Brazil. The associated factors to higher medication adherence were lower disease activity by BASDAI, being non-white race, and intravenous drug use. The associated factors to higher medication persistence were lower disease activity by Bath Ankylosing Spondylitis Activity Index (BASDAI), intravenous drug use, non-use of corticoids and non-steroidal anti-inflammatory drugs, and comorbidity.Conclusions:Patients with medication adherence and persistence had significant improvements in clinical measures, functionality, and quality of life. High medication adherence and persistence to biological therapy were observed and associated with lesser disease activity at baseline. Also, medication persistence to PsA patients attended in specialty pharmacy was higher than the overall PsA population in Brazil, which indicates the importance of pharmaceutical services to provide health care and promote the effectiveness and safety of biological therapies.

Biothérapies dans l’asthme sévère de l’enfant et de l’adolescent: Biotherapies in severe asthma in children and adolescents

Thanks to a better understanding of the role of type 2 inflammation in allergic asthma, progress has been made in the development of new biologic therapies targeting these specific pathways. After adults, these treatments are now available for children. However, with the exception of Omalizumab, an anti-IgE immunoglobulin, very few studies have been published on the efficacy and safety of biologic therapies in children, in particular anti-interleukin-5 (IL5) and anti-IL4/IL13 therapies. After exclusion of differential diagnoses, exclusion if difficult to treat asthma and phenotyping, a personalized biologic therapy could be proposed with specificities in children regarding the initiation, follow-up and duration of treatment.© 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.