[Effectiveness and safety of biological therapy in patients with severe asthma in a real clinical practice].

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.

Magnetic resonance enterography findings 46 weeks after initiation of biological therapy predict long-term adverse outcomes in Crohn's disease.

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.

Safety of Biological Therapies for Severe Asthma: An Analysis of Suspected Adverse Reactions Reported in the WHO Pharmacovigilance Database.

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.

Impact of biological therapy in reducing the risk of arthritis development in inflammatory bowel diseases.

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.

Comparative Effectiveness of Biologic Therapies in Preventing Penetrating Complications in Patients With Crohn's Disease.

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.

RISK FACTORS FOR EARLY POSTOPERATIVE COMPLICATIONS IN ACUTE COLITIS IN THE ERA OF BIOLOGIC THERAPY.

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.

Cutaneous immune-related phenomena in patients with inflammatory arthritides treated with biological therapies: Clinical and pathophysiological considerations.

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.

Biological therapies for hemophagocytic lymphohistiocytosis: current knowledge and future perspectives.

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.

Type 2 inflammation and biological therapies in asthma: Targeted medicine taking flight.

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.

The predictors of paradoxical reactions, especially psoriasis, to biologic therapy-findings from the TReasure database: a 5-year follow-up study.

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.

Biotherapy of experimental acute kidney injury: emerging novel therapeutic strategies.

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.

Impact of biologic therapies on risk of adverse cardiovascular events in patients with Ankylosing Spondylitis or Psoriatic Arthritis: A systematic literature review.

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.

Insights into atopic dermatitis pathogenesis lead to newly approved systemic therapies.

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.

Cardiotoxicity of Biological Therapies in Cancer Patients: An In-depth Review.

Cardiotoxicity from chemotherapy regimens has been long reported. However, the understanding of cardiac side effects of biological therapies is rapidly evolving. With cancer patients achieving higher life expectancy due to the use of personalized medicine and novel targeted anticancer agents, the occurrence of cardiotoxicity is becoming more significant. Novel biological therapies include anti-HER2 antibodies, tyrosine kinase inhibitors, bruton kinase inhibitors, antivascular endothelial growth factors, proteasome inhibitors, immunomodulator drugs, and immune checkpoint inhibitors. Potential cardiovascular toxicities linked to these anticancer agents include hypertension, arrhythmias, QT prolongation, myocardial ischemia and infarction, left ventricular dysfunction, congestive heart failure, and thromboembolism. Cardiac biomarkers, electrocardiography, echocardiography and magnetic resonance imaging are common diagnostic modalities used for early detection of these complications and timely intervention. This review discusses the various types of cardiotoxicities caused by novel anticancer biologic agents, their molecular and pathophysiological mechanisms, risk factors, and diagnostic and management strategies that can be used to prevent, minimize, and treat them.

Influence of biologic therapy on cardiovascular risk factors in patients with inflammatory bowel disease. / Influencia del tratamiento biológico en los factores de riesgo cardiovascular de los pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Chronic immune-mediated diseases, including inflammatory bowel disease (IBD), present an increased risk of developing early atherosclerosis and cardiovascular events (CVE) at early age. OBJECTIVE: To describe the baseline and 1-year cardiovascular profile of patients with IBD according to the biologic treatment received, taking into account the inflammatory activity. PATIENTS AND METHODS: It is a retrospective, observational study that included 374 patients. Cardiovascular risk factors (CVRF) and CVE were collected at the baseline visit and at one-year follow-up to describe the cardiovascular risk according to the biological treatment received, also assessing clinical and biological remission. RESULTS: A total of 374 patients were included: 146 (38.73%) were treated with Infliximab, 128 (33.95%) with adalimumab, 61 (16.18%) with ustekinumab and 42 (11.14%) with vedolizumab. The changes in blood glucose levels are [86.31mg/dL (84.57-88.06) vs. 89.25mg/dL (87.54-90.96), P=.001] for those treated with antiTNFα and [86.52mg/dL (83.48-89.55) vs. 89.44mg/dL (85.77-93.11), P=.11] in the other group. In the group treated with antiTNFα total cholesterol values at baseline visit are [169.40mg/dL (164.97-173.83) vs. 177.40mg/dL (172.75-182.05) at one year of treatment, P=<.001], those of HDL [50.22mg/dL (48.39-52.04) vs. 54.26mg/dL (52.46-56.07), P=<.001] and those of triglycerides [114.77mg/dL (106.36-123.18) vs. 121.83mg/dL (112.11-131.54), P=.054]. Regarding weight, an increase was observed, both in those patients treated with antiTNFα [71.39kg (69.53-73.25) vs. 72.87kg (71.05-74.70), P<.001], and in the group treated with ustekinumab and vedolizumab [67.59kg (64.10-71.08) vs. 69.43kg (65.65-73.04), P=.003]. Concerning CVE, no significant differences were observed neither according to the drug used (p=0.36), nor according to personal history of CVE (P=.23) nor according to inflammatory activity (P=.46). CONCLUSIONS: Our results on a real cohort of patients with IBD treated with biologic drugs show a better control of certain cardiovascular parameters such as CRP or HDL, but a worsening of others such as total cholesterol or triglycerides, regardless of the treatment. Therefore, it is possibly the disease control and not the therapeutic target used, the one that affect the cardiovascular risk of these patients.

COVID-19 vaccination rate and willingness of an additional dose among inflammatory bowel disease patients receiving biologic therapy: Fearless and with desire.

Effective vaccines against the SARS-CoV-2 are already available and offer a promising action to control the COVID-19 pandemic. IBD patients on biological agents accept the vaccine as well as an additional dose if recommended. BACKGROUND: Vaccination against COVID-19 prevents its severe forms and associated mortality and offers a promising action to control this pandemic. In September 2021, an additional dose of vaccine was approved in patients with immunosuppression including IBD patients on biologic agents. We evaluated the vaccination rate and additional dose willingness in this group of at risk patients. METHODS: A single-center, cross-sectional study was performed among IBD patients on biologic agents and eligible for an additional dose of the COVID-19 vaccine. IBD clinical characteristics and type of vaccine and date of administration were checked in medical records. Acceptance was evaluated after telephone or face-to-face surveys in IBD patients. RESULTS: Out of a total of 344 patients, 269 patients (46.1% male; mean age 47±16 years; Crohn's disease 73.6%) were included. Only 15 (5.6%) patients refused the COVID-19 vaccine mainly (40%) for conviction (COVID-19 pandemic denial). 33.3% would re-consider after discussing with their doctor and/or receiving information on the adverse effects of the vaccine. Previous to the additional dose, the COVID-19 vaccination was present in 94.4% of patients (n=254). Adverse effects occurred in 53.9% of the cases, mainly pain in the arm (40%). Up to 94.1% of the patients agreed to an additional dose and 79.4% had already received the additional dose at the final time of the assessment. CONCLUSIONS: IBD patients on biological agents accept the vaccine as well as an additional dose if recommended. Physicians in charge of IBD units should provide information and confidence in the use of the vaccine in these IBD patients.

Biologic Therapy Carries a Very Low Risk of Reactivation in Hepatitis B Surface Antigen-Negative Phase of Hepatitis B.

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.