ABSTRACT
BACKGROUND/OBJECTIVES: Royal Darwin Hospital (RDH) is the sole public dermatology service in the Northern Territory (NT). Prescription of biologic therapies (BT) in the NT is uniquely challenging, with remote populations carrying a high tropical disease burden. The aim of this audit is to examine the demographics and outcomes of patients on BT for dermatologic conditions. METHODS: Retrospective case note review of patients receiving BT through the RDH Dermatology department between August 2021 and October 2023. Data analysed were demographics, location, dermatological diagnosis and serology status. RESULTS: In this audit, 115 patients were included. Age range of 13-91 years, mean of 51.1 years (±14.7), 52 (45.2%) patients were female and 8 (7.8%) identified as First Nations Australian. A large geographical area was serviced, with a primary address between 1 and 1496 km from RDH. Eighteen patients (15.7%) have discontinued BT completely. There was a statistically significant relationship between cessation of BT and increased distance of primary residence from RDH (p < 0.0007). Eighteen patients (15.7%) required management of infections identified in opportunistic infection screening. These infections were strongyloidiasis, tuberculosis, melioidosis and hepatitis B. CONCLUSIONS: There is significant anxiety surrounding BT and tropical infections, including in returning travellers in southern Australian states. There has been particular interest in strongyloidiasis infection, as dupilumab acts on the Th2 immunity mechanism critical to parasitic infection response. This audit exhibits the unique experience of dermatological care in a tropical setting, demonstrating how BT can be used safely and how, when identified, these tropical infections can be successfully managed.
Subject(s)
Opportunistic Infections , Humans , Female , Middle Aged , Male , Adult , Aged , Retrospective Studies , Northern Territory/epidemiology , Adolescent , Young Adult , Aged, 80 and over , Opportunistic Infections/epidemiology , Skin Diseases , Biological Therapy/adverse effectsSubject(s)
Hepatitis B virus , Hepatitis B , Psoriasis , Virus Activation , Humans , Psoriasis/drug therapy , Psoriasis/immunology , Retrospective Studies , Hepatitis B virus/immunology , Hepatitis B virus/physiology , Virus Activation/drug effects , Virus Activation/immunology , Male , Female , Middle Aged , Hepatitis B/drug therapy , Hepatitis B/immunology , Adult , Aged , Biological Therapy/adverse effects , Biological Therapy/methods , Risk Factors , Biological Products/therapeutic use , Biological Products/adverse effectsABSTRACT
AIM: To assess effectiveness and safety of biological therapy in patients with severe asthma during 5 yr follow-up. MATERIALS AND METHODS: We recruited 129 adult outpatients (29% males) aged 18-81 yrs with severe asthma were followed up during 5 yrs and were examined for every 3-6 months. Eighty five patients were treated by conventional therapy (ICS/LABA ± tiotropium, montelukast, OCS) only and 44 pts additionally received biologicals (оmalizumab - 9 pts, мepolizumab - 8 pts, benralizumab - 11 pts, dupilumab - 16 pts). Pulmonary function tests were measured by dry spirometer (2120, Vitalograph Ltd., UK). Eosinophil count in blood was assessed by automatic haemoanalyser. Fraction of exhaled nitric oxide was measured by a chemiluminescence analyzer (LR4100; Logan Research, UK). Asthma control and quality of life were assessed by using Russian versions of ACQ-5 and SGRQ. RESULTS: The use of biologicals led to a more significant reduction of exacerbations and OCS use, improvement of lung function, asthma control and quality of life, decrease of eosinophil and fraction of exhaled nitric oxide than conventional therapy of severe asthma (p<0.05). Systemic side effects were not registered, frequency of local adverse reactions (edema, hyperemia and itching at injection site) was 14%. CONCLUSION: Long-term use of biologicals added to conventional therapy in patients with severe asthma is characterized by high effectiveness and favorable safety profile.
Subject(s)
Asthma , Humans , Asthma/drug therapy , Asthma/physiopathology , Male , Female , Middle Aged , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Anti-Asthmatic Agents/administration & dosage , Anti-Asthmatic Agents/adverse effects , Anti-Asthmatic Agents/therapeutic use , Severity of Illness Index , Quality of Life , Respiratory Function Tests/methods , Treatment Outcome , Aged , Biological Therapy/methods , Biological Therapy/adverse effects , Young Adult , AdolescentABSTRACT
BACKGROUND AND AIMS: Magnetic resonance enterography (MRE) depicts transmural changes in response to biological treatment for Crohn's disease (CD); however, the long-term prognostic significance of these findings is unknown. The primary objective of this study was to identify findings on MRE 46 weeks after initiating biological treatment that predict adverse long-term outcomes. METHODS: Patients with CD underwent MRE 46 weeks after initiating biological treatment and were prospectively followed for 2 years. A logistic regression analysis was performed to assess the prognostic value of different radiologic findings for various predefined adverse outcomes. RESULTS: Of the 89 patients included, 46 (51.7%) had ≥1 adverse outcome during follow-up: 40 (44.9%) had clinical recurrence; 18 (20.2%) required surgery, 8 (9%) endoscopic balloon dilation, 12 (13.5%) hospitalization and 7 (7.8%) required corticosteroids. In the multivariate analysis, persistence of severe lesions (MaRIA ≥11) in any intestinal segment was associated with an increased risk of surgery [OR 11.6 (1.5-92.4)], of surgery and/or endoscopic balloon dilation [OR 6.3 (1.3-30.2)], and of clinical relapse [OR 4.6 (1.6-13.9)]. Penetrating lesions were associated with surgery [OR 3.4 (1.2-9.9)]. Creeping fat with hospitalization [OR 5.1 (1.1-25.0)] and corticosteroids requirement [OR 16.0 (1.2-210.0)]. The presence of complications (stricturing and/or penetrating lesions) was associated with having ≥1 adverse outcome [OR 3.35 (1.3-8.5)]. CONCLUSION: MRE findings at week-46 after initiating biological therapy can predict long-term adverse outcomes in CD. Therapeutic intervention may be required in patients with persistence of severe inflammatory lesions, CD-associated complications, or creeping fat.
Subject(s)
Crohn Disease , Magnetic Resonance Imaging , Humans , Crohn Disease/diagnostic imaging , Crohn Disease/drug therapy , Female , Male , Adult , Magnetic Resonance Imaging/methods , Prospective Studies , Middle Aged , Prognosis , Treatment Outcome , Young Adult , Recurrence , Biological Therapy/adverse effects , Biological Therapy/methods , Follow-Up StudiesABSTRACT
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a type2 inflammatory disease of the upper airways, with severe impairment of quality of life. Persons affected by NSAID-exacerbated respiratory disease (NERD) usually present with highly dynamic recurrence of polyps and disease despite prior treatment with sinus surgeries, oral corticosteroids, and aspirin desensitization (ATAD). Biologic therapy has fundamentally changed the choice of therapeutic concept; however, limited data exist on subgroups such as NERD patients. The aim of the current article is to report on a multicenter retrospective study on add-on therapy with dupilumab, omalizumab, and mepolizumab in patients with NERD. METHODS: This is a retrospective cohort study of patients (NERD+, status after ATAD) in three reference centers in Germany (Munich, Mainz, Berlin). Subjective and objective parameters were collected at 4, 8, and 12 months after biologic therapy initiation in accordance with current EPOS/EUFOREA (European Position Paper on Rhinosinusitis and Nasal Polyps/European Forum for Research and Education in Allergy and Airway Diseases) guidelines. Biologic agents were chosen depending on availability and patient characteristics. RESULTS: Treatment was commenced in 122 patients meeting the criteria for CRSwNP and NERD. The endoscopic polyp score, SNOT-22 questionnaire score, visual analogue scoring of total symptoms/severity of disease, and sense of smell (psychophysical testing with Sniffin'Sticks/Brief Smell Identification Test, BSIT; Sensonics, Inc., Haddon Heights, NJ, USA) improved significantly after 4 and 12 months of add-on therapy (pâ¯< 0.0001). All three biologic agents significantly improved one or more disease parameter. Adverse events were not life threatening but led to change of biologic agent in 4 cases. Patients rated biologic therapy significantly better than ATAD, with improved long-term disease control. CONCLUSION: Add-on biologic therapy is effective, safe, and widely accepted among CRSwNPâ¯+ NERD patients. Future studies might allow for personalized algorithms with sequential surgery, ATAD, and/or biologic therapy.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Aspirin , Humans , Female , Male , Middle Aged , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Germany , Retrospective Studies , Aspirin/adverse effects , Treatment Outcome , Desensitization, Immunologic/methods , Sinusitis/chemically induced , Sinusitis/drug therapy , Sinusitis/therapy , Adult , Nasal Polyps/drug therapy , Asthma, Aspirin-Induced/therapy , Asthma, Aspirin-Induced/diagnosis , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Biological Therapy/methods , Biological Therapy/adverse effects , Rhinitis/chemically induced , Rhinitis/therapy , Omalizumab/therapeutic use , Omalizumab/adverse effects , Cohort Studies , Aged , Chronic DiseaseABSTRACT
BACKGROUND: The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for the type 2 asthma phenotype: anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4 (dupilumab) monoclonal antibodies. These drugs are usually well tolerated, although long-term safety information is limited, and some adverse events have not yet been fully characterized. Spontaneous reporting systems represent the cornerstone for the detection of potential signals and evaluation of the real-world safety of all marketed drugs. OBJECTIVE: The aim of this study was to provide an overview of safety data of biologics for severe asthma using VigiBase, the World Health Organization global pharmacovigilance database. METHODS: We selected all de-duplicated individual case safety reports (ICSRs) attributed to five approved biologics for severe asthma in VigiBase, up to 31st August 2022 (omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab). Descriptive frequency analyses of ICSRs were carried out both as a whole class and as individual products. Reporting odds ratios (ROR) with 95% confidence intervals (CIs) were used as the measure of disproportionality for suspected adverse drug reactions (ADRs) associated with the study drugs compared with either all other suspected drugs (Reference Group 1, RG1) or inhaled corticosteroids plus long-acting ß-agonists (ICSs/LABAs) (Reference Group 2, RG2) or with oral corticosteroids (OCSs) (Reference Group 3, RG3). RESULTS: Overall, 31,724,381 ICSRs were identified in VigiBase and 167,282 (0.5%) were related to study drugs; the remaining reports were considered as RG1. Stratifying all biologic-related ICSRs by therapeutic indication, around 29.4% (n = 48,440) concerned asthma use; omalizumab was mainly indicated as the suspected drug (n = 20,501), followed by dupilumab, mepolizumab, benralizumab and reslizumab. Most asthma ICSRs concerned adults (57%) and women (64.1%). Asthma biologics showed a higher frequency of serious suspected ADR reporting than RG1 (41.3% vs 32.3%). The most reported suspected ADRs included asthma, dyspnea, product use issue, drug ineffective, cough, headache, fatigue and wheezing. Asthma biologics were disproportionally associated with several unknown or less documented adverse events, such as malignancies, pulmonary embolism and deep vein thrombosis with omalizumab; alopecia and lichen planus with dupilumab; alopecia and herpes infections with mepolizumab; alopecia, herpes zoster and eosinophilic granulomatosis with polyangiitis related to benralizumab; and alopecia with reslizumab. CONCLUSIONS: The most frequently reported suspected ADRs of asthma biologics in VigiBase confirmed the presence of well-known adverse effects such as general disorders, injection-site reactions, nasopharyngitis, headache and hypersensitivity, while some others (e.g. asthma reactivation or therapeutic failure) could be ascribed to the indication of use. Moreover, the analysis of signals of disproportionate reporting suggests the presence of malignancies, effects on the cardiovascular system, alopecia and autoimmune conditions, requiring further assessment and investigation.
Subject(s)
Anti-Asthmatic Agents , Asthma , Pharmacovigilance , World Health Organization , Humans , Asthma/drug therapy , Anti-Asthmatic Agents/adverse effects , Anti-Asthmatic Agents/therapeutic use , Female , Male , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Databases, Factual , Adult , Biological Therapy/adverse effects , Biological Therapy/methods , Middle Aged , Aged , Omalizumab/therapeutic use , Omalizumab/adverse effects , Biological Products/adverse effects , Biological Products/therapeutic useABSTRACT
BACKGROUND: Optimizing second-line biologic therapies for adult ulcerative colitis (UC) post first-line failure is essential. OBJECTIVE: Compare second-line biologic therapy efficacy in adult UC patients with prior treatment failure. METHODS: A comprehensive search of electronic databases up to May 2023 was conducted to assess second-line biologic therapy efficacy using a random effects model. Parameters analyzed included clinical remission rate, clinical response rate, mucosal healing rate, annual discontinuation rate, and colectomy rates. RESULTS: Forty-three research papers were analyzed. Clinical remission rates for second-line biologics were ranked at 6-14 weeks: Infliximab (30%) was followed by Vedolizumab (29%), Ustekinumab (27%), and Adalimumab (19%). At 52-54 weeks, the order shifted, with Vedolizumab (35%) followed by Infliximab (32%), Ustekinumab (31%), and Adalimumab (26%). The mucosal healing rate was 21%, ranked as: Infliximab (31%), Vedolizumab (21%), Adalimumab (21%), and Ustekinumab (14%). The annual discontinuation rate stood at 20%, with Adalimumab (25%), Vedolizumab (18%), Infliximab (17%), and Ustekinumab (16%). Discontinuation rates due to primary failure (PF), secondary failure (SF), and adverse events (AE) were 6%, 12%, and 3%, respectively. The annual colectomy rate was 9%, with Adalimumab (15%) followed by Vedolizumab (10%), Ustekinumab (9%), and Infliximab (5%), and colectomy rates of 10% due to PF, 12% due to SF, and 4% due to AE. CONCLUSION: For UC patients with first-line treatment failure, it is recommended to prioritize infliximab or vedolizumab as second-line biologic therapies, while avoiding adalimumab as the primary choice. Further clinical trials are necessary to assess ustekinumab efficacy accurately.
Subject(s)
Colitis, Ulcerative , Treatment Failure , Humans , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/surgery , Biological Therapy/methods , Biological Therapy/adverse effects , Adult , Biological Products/therapeutic use , Biological Products/adverse effects , Gastrointestinal Agents/therapeutic use , Gastrointestinal Agents/adverse effects , Infliximab/therapeutic use , Antibodies, Monoclonal, HumanizedABSTRACT
OBJECTIVE: Evaluate spondyloarthritis (SpA) incidence in inflammatory bowel diseases (IBD) between patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) and conventional DMARDs (cDMARDs) and define risk factors associated with SpA development. METHODS: Retrospective cohort study was conducted on patients with Crohn's disease (CD) or ulcerative colitis (UC) and divided into two cohorts: cDMARDs or bDMARDs/targeted synthetic (ts) DMARDs treated patients. Rheumatological assessment was performed in patients presenting musculoskeletal symptoms. Multivariate analysis and Kaplan-Meier curves were used to evaluate the adjusted SpA risk development. RESULTS: 507 patients were included in the study. 176 patients with CD received bDMARDs, 112 cDMARDs and 106 new SpA diagnosies were formulated. Females (OR 1.7 (95% CI 1.1 to 3), adjusted p=0.04), non-stricturing/non-penetrating phenotype (OR 2 (95% CI 1.1 to 3.4), adjusted p=0.01), psoriasis (OR 2.1 (95% CI 1 to 4.6), adjusted p=0.04) and non-infectious uveitis (OR 6.8 (95% CI 1.4 to 33.4), adjusted p=0.01) were associated with increased SpA risk development, while bDMARDs usage was protective (OR 0.4 (95% CI 0.2 to 0.8), adjusted p=0.01), statistically higher than cDMARDs throughout the entire follow-up (effect size 0.47). 98 patients with UC received b-tsDMARDs, 121 cDMARDs and 56 new SpA diagnoses were formulated. Females (OR 2.1 (95% CI 1 to 4.3), adjusted p=0.02) and psoriasis (OR 2.7 (95% CI 1 to 6.8), adjusted p=0.03) were associated with increased SpA risk development, while bDMARDs were protective for SpA development for up to 12 months of treatment compared with cDMARDs (p=0.03). CONCLUSIONS: bDMARDs treatment had an impact in reducing SpA development and clinical associated risk factors to transition from IBD to IBD-SpA emerged.
Subject(s)
Antirheumatic Agents , Inflammatory Bowel Diseases , Psoriasis , Spondylarthritis , Female , Humans , Retrospective Studies , Antirheumatic Agents/adverse effects , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Spondylarthritis/complications , Spondylarthritis/drug therapy , Spondylarthritis/epidemiology , Psoriasis/epidemiology , Biological Therapy/adverse effectsABSTRACT
BACKGROUND & AIMS: Comparative effectiveness of biologics in preventing penetrating disease (PD) in Crohn's disease (CD) is not well established. We compared the risk of developing luminal and perianal PD (LPD and PPD) between biologics used as first-line therapies. METHODS: Adults (>17 years) with CD who initiated their first biologic (anti-tumor necrosis factor [anti-TNF], ustekinumab [UST], or vedolizumab [VDZ]) were identified from Merative Commercial Database (2006 and 2020). We excluded preexisting PD using a minimum look-back period of 1 year. Cohorts were balanced by inverse probability of treatment weighting based on age, sex, comorbidities, prior CD surgery, and CD severity. Pairwise comparisons were performed by Cox proportional hazards models, adjusted for immunomodulator exposure, and with biologic exposure treated as a time-dependent variable based on a medication possession ratio of 0.8. RESULTS: Our analysis included 40,693 patients: 93% anti-TNF, 3% UST, and 4% VDZ. After inverse probability of treatment weighting all comparisons were well balanced. Anti-TNF was protective against LPD (hazard ratio, 0.66; 95% confidence interval, 0.55-0.78; P < .0001) and PPD (hazard ratio, 0.88; 95% confidence interval, 0.80-0.96; P = .0045) compared with VDZ and LPD (hazard ratio, 0.37; 95% confidence interval, 0.30-0.46; P < .0001) compared with UST. There were no significant differences in the risk of LPD and PPD between VDZ and UST. These results were similar after limiting the study period to after 2016. CONCLUSIONS: Anti-TNF therapy was associated with a lower risk of LPD and PPD compared with VDZ, and lower risk of LPD compared with UST. Further studies are needed to validate these findings and to determine potential reasons for these differences.
Subject(s)
Biological Products , Crohn Disease , Adult , Humans , Crohn Disease/drug therapy , Crohn Disease/complications , Tumor Necrosis Factor Inhibitors/therapeutic use , Ustekinumab/therapeutic use , Tumor Necrosis Factor-alpha/therapeutic use , Biological Therapy/adverse effects , Biological Products/adverse effects , Retrospective Studies , Treatment OutcomeABSTRACT
In recent years, identifying the pathophysiologic mechanisms underlying autoimmune arthritides and systematic diseases has led to the use of biological drugs. The primary targets of those biological therapies are cytokines, B cells, and co-stimulation molecules. So far, these targeted therapies have shown good clinical improvement and an acceptable toxicity profile. However, by blocking components of an intact immune system, autoimmune phenomena and paradoxical inflammation have emerged, and among them many cutaneous immune-related adverse events (irAEs). In this article, we review the current state of knowledge on the clinical features and mechanisms of specific cutaneous irAEs observed during treatment with biological therapies. Among those, psoriatic skin lesions are the most commonly observed. Herein, we also report new cases of cutaneous irAEs recently seen in our clinic to help physicians treating inflammatory arthritides recognize cutaneous irAEs early and better manage patients receiving biologic therapies.
Subject(s)
Arthritis , Neoplasms , Humans , Biological Therapy/adverse effects , Skin , Cytokines , Neoplasms/drug therapyABSTRACT
BACKGROUND: Despite major advances in the clinical treatment of inflammatory bowel disease, some patients still present with acute colitis and require emergency surgery. AIMS: To evaluate the risk factors for early postoperative complications in patients undergoing surgery for acute colitis in the era of biologic therapy. METHODS: Patients with inflammatory bowel disease admitted for acute colitis who underwent total colectomy at a single tertiary hospital from 2012 to 2022 were evaluated. Postoperative complications were graded according to Clavien-Dindo classification (CDC). Patients with more severe complications (CDC≥2) were compared with those with less severe complications (CDC<2). RESULTS: A total of 46 patients underwent surgery. The indications were: failure of clinical treatment (n=34), patients' or surgeon's preference (n=5), hemorrhage (n=3), toxic megacolon (n=2), and bowel perforation (n=2). There were eight reoperations, 60.9% of postoperative complications classified as CDC≥2, and three deaths. In univariate analyses, preoperative antibiotics use, ulcerative colitis diagnosis, lower albumin levels at admission, and preoperative hospital stay longer than seven days were associated with more severe postoperative complications. CONCLUSIONS: Emergency surgery for acute colitis was associated with a high incidence of postoperative complications. Preoperative use of antibiotics, ulcerative colitis, lower albumin levels at admission, and delaying surgery for more than seven days were associated with more severe early postoperative complications. The use of biologics was not associated with worse outcomes.
Subject(s)
Colitis, Ulcerative , Colitis , Inflammatory Bowel Diseases , Humans , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/surgery , Colitis, Ulcerative/complications , Retrospective Studies , Colitis/surgery , Inflammatory Bowel Diseases/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Colectomy/adverse effects , Risk Factors , Biological Therapy/adverse effects , Anti-Bacterial Agents , AlbuminsABSTRACT
INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome with a dismal prognosis. The underlying causes of HLH are diverse. However, the overabundance of cytokines was shared by all forms of HLH. Cytokine-targeted biotherapies have been increasingly used in HLH treatment. AREAS COVERED: In this review, we aim to provide an overview of biological treatment options for HLH. EXPERT OPINION: Biological therapies offer alternative treatment options for patients with refractory/relapsed HLH or who are intolerant to conventional chemotherapies. As a complement to traditional treatment, biological agents improve response rates, maintain more protracted periods of remission, and reduce treatment related toxicity. A combination of biological agents may be a promising direction for HLH treatment. However, they may induce HLH to deteriorate and even trigger HLH.
Subject(s)
Lymphohistiocytosis, Hemophagocytic , Humans , Lymphohistiocytosis, Hemophagocytic/drug therapy , Lymphohistiocytosis, Hemophagocytic/etiology , Cytokines/therapeutic use , Biological Therapy/adverse effectsABSTRACT
OBJECTIVES: The objectives of this study were to assess the clinical characteristics, predictive factors, and practical algorithms of paradoxical reactions (PRs), specifically paradoxical psoriasis (PP). METHODS: The TReasure database is a web-based prospective observational cohort comprised of patients with RA and SpA from 17 centres around Turkey since 2017. A cohort study and a case-control study nestled within the cohort were identified. RESULTS: In total, 2867 RA and 5316 SpA patients were evaluated. The first biologic agent was found to have caused PRs in 60% of the 136 patients (1.66%) who developed the PRs. The median time interval between the PRs and biological onset was 12 months (range 1-132 months, mean 21 months). The most common types of PP, constituting 92.6% of PRs, were pustular (60.3%) and palmoplantar (30.9%). Adalimumab (30.9%), infliximab (19%) and etanercept (17.4%) were the most common agents causing the PP. In the treatment of most PP patients (73.2%), switching biologic agents was favoured, with TNF inhibitor (TNFi) chosen in 46.03% and non-TNFi in 26.9% of cases. The three most frequently selected drugs were etanercept (24.6%), secukinumab (9.5%) and adalimumab (8.7%). Only 5.17% of patients who switched to another TNFi showed progression. The odds ratios (s) for SSZ, HCQ, and LEF use were significantly higher in RA controls than in PP patients (P = 0.033, OR = 0.15; P = 0.012, OR = 0.15; and P = 0.015, OR = 0.13, respectively). In the PP group with SpA, the number of smokers was significantly higher (P = 0.003, OR: 2.0, 95% CI: 1.05, 3.81). CONCLUSION: Contrary to expectations based on earlier research suggesting that paradoxical reactions develop with the class effect of biological agents, the response of patients who were shifted to another TNFi was favourable.
Subject(s)
Antirheumatic Agents , Psoriasis , Humans , Adalimumab/adverse effects , Antirheumatic Agents/adverse effects , Biological Factors/adverse effects , Biological Therapy/adverse effects , Case-Control Studies , Cohort Studies , Etanercept/adverse effects , Follow-Up Studies , Infliximab/adverse effects , Psoriasis/drug therapy , Psoriasis/chemically induced , Tumor Necrosis Factor Inhibitors , Tumor Necrosis Factor-alphaABSTRACT
Acute kidney injury (AKI) is a complex and heterogeneous disease with high incidence and mortality, posing a serious threat to human life and health. Usually, in clinical practice, AKI is caused by crush injury, nephrotoxin exposure, ischemia-reperfusion injury, or sepsis. Therefore, most AKI models for pharmacological experimentation are based on this. The current research promises to develop new biological therapies, including antibody therapy, non-antibody protein therapy, cell therapy, and RNA therapy, that could help mitigate the development of AKI. These approaches can promote renal repair and improve systemic hemodynamics after renal injury by reducing oxidative stress, inflammatory response, organelles damage, and cell death, or activating cytoprotective mechanisms. However, no candidate drugs for AKI prevention or treatment have been successfully translated from bench to bedside. This article summarizes the latest progress in AKI biotherapy, focusing on potential clinical targets and novel treatment strategies that merit further investigation in future pre-clinical and clinical studies.
Subject(s)
Acute Kidney Injury , Reperfusion Injury , Sepsis , Humans , Acute Kidney Injury/therapy , Kidney/metabolism , Cell Death , Sepsis/therapy , Biological Therapy/adverse effectsABSTRACT
The field of asthma has undergone a dramatic change in recent years. Advances in our understanding of type 2 airway inflammation have driven the discovery of monoclonal antibodies targeting specific aspects of the immune pathway. In landmark trials, these drugs have shown efficacy in reducing asthma attacks and exposure to oral corticosteroids, important causes of morbidity in people with asthma. Our review explores the key features of type 2 inflammation in asthma and summarizes the clinical trial evidence of the novel monoclonal antibody treatments and future avenues for treatment.
Subject(s)
Asthma , Humans , Antibodies, Monoclonal/therapeutic use , Inflammation/complications , Biological Therapy/adverse effectsABSTRACT
BACKGROUND: Recent evidence highlights increased mortality and morbidity due to cardiovascular disease (CVD), especially within the two major forms of Spondyloarthropathies (SpAs), Ankylosing Spondylitis (AS) and Psoriatic Arthritis (PsA). Healthcare professionals and patients in these populations should be alerted regarding the high risk of cardiovascular (CV) events and thus, customize the treatment strategy accordingly. OBJECTIVE: This systematic literature review aimed to determine the effects of biological therapies on serious CV events in AS and PsA. METHODS: Screening for the study was carried out using PubMed and Scopus databases from the database's inception to the 17th of July 2021. The literature search strategy for this review is based on the Population, Intervention, Comparator, Outcomes (PICOs) framework. Randomized controlled trials (RCTs) of biologic therapies for the treatment of AS and/or PsA were included. The primary outcome measure was the number of serious CV events reported during the placebo-controlled phase. RESULTS: 4,422 articles were generated from keywords, eligibility criteria, and databases. Following the screening, we retained 13 studies for analysis: 3 in AS and 10 in PsA. Meta-analysis of results was not feasible due to the small number of the identified studies, the heterogeneity of the biologic treatment and the included populations, as well as the infrequently reported requested endpoint. According to our review, biologic treatments are safe options as for CV risk in patients with PsA or AS. CONCLUSION: Further and more extensive trials in AS/PsA patients at high risk of CV events are needed before firm conclusions can be drawn.
Subject(s)
Arthritis, Psoriatic , Biological Products , Cardiovascular Diseases , Spondylitis, Ankylosing , Humans , Arthritis, Psoriatic/complications , Biological Products/adverse effects , Biological Therapy/adverse effects , Cardiovascular Diseases/epidemiology , Spondylitis, Ankylosing/complicationsABSTRACT
Atopic dermatitis (AD) is a common inflammatory skin disease characterized by scaly, oozing skin and itch. In moderate-to-severe AD, treatment options have been historically very limited and off-label use has been a common method for disease management. For decades, ciclosporin A was the only systemic immunosuppressive drug approved in most European countries to address this major unmet medical need. However, increased understanding of the pathophysiology of AD has led to a revolution in the treatment of this potentially debilitating disease. Following the approval of the first biological therapy for AD in 2017, there has been a rapid expansion of compounds under development and four additional systemic therapies have been approved in Europe and the USA within the past 3 years alone. In this review, we underscore how key breakthroughs have transformed the therapeutic landscape of AD, leading to a major expansion of type 2 immunity-targeted biological therapies, exploration of neuroimmune modulatory agents, and interest in Janus kinase inhibition.
Subject(s)
Dermatitis, Atopic , Humans , Immunosuppressive Agents/therapeutic use , Cyclosporine/therapeutic use , Biological Therapy/adverse effects , EuropeABSTRACT
BACKGROUND: The risk of hepatitis B reactivation in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients exposed to biologic agents is not clear. We aimed to investigate the reactivation rate in hepatitis B surface antigen-negative phase of hepatitis B virus-infected patients after biologic therapy. METHODS: Patients followed at gastroenterology, rheumatology, and dermatology clinics with a diagnosis of immune-mediated inflam matory diseases were screened. Immune-mediated inflammatory diseases patients exposed to biologic agents with a negative hepatitis B surface antigen and positive hepatitis B core immunoglobulin G antibody were included in the study. RESULTS: We screened 8266 immune-mediated inflammatory disease patients, and 2484 patients were identified as exposed to biologic agents. Two hundred twenty-one patients were included in the study. The mean age was 54.08 ± 11.69 years, and 115 (52.0%) patients were female. The median number of different biologic subtype use was 1 (range: 1-6). The mean biologic agent exposure time was 55 (range: 2-179) months. One hundred and fifty-two (68.8%) patients used a concomitant immunomodulatory agent, and 84 (38.0%) patients were exposed to corticosteroids during biologic use. No hepatitis B reactivation with a reverse seroconversion of hepatitis B surface antigen positivity was seen. Antiviral prophylaxis for hepatitis B was applied to 48 (21.7%) patients. Hepatitis B virus-DNA was screened in 56 (25.3%) patients prior to the biologic exposure. Two patients without antiviral prophylaxis had hepatitis B virus-DNA reactivation with a negative hepatitis B surface antigen during exposure to the biologic agent. CONCLUSION: We found 2 reactivations and no hepatitis B surface antigen seroconversion in our cohort. Antiviral prophylaxis for patients exposed to biologic agents may need to be discussed in more detail.