Eosinophil Knockout Humans: Uncovering the Role of Eosinophils Through Eosinophil-Directed Biological Therapies.

The enigmatic eosinophil has emerged as an exciting component of the immune system, involved in a plethora of homeostatic and inflammatory responses. Substantial progress has been achieved through experimental systems manipulating eosinophils in vivo, initially in mice and more recently in humans. Researchers using eosinophil knockout mice have identified a contributory role for eosinophils in basal and inflammatory processes and protective immunity. Primarily fueled by the purported proinflammatory role of eosinophils in eosinophil-associated diseases, a series of anti-eosinophil therapeutics have emerged as a new class of drugs. These agents, which dramatically deplete eosinophils, provide a valuable opportunity to characterize the consequences of eosinophil knockout humans. Herein, we comparatively describe mouse and human eosinophil knockouts. We put forth the view that human eosinophils negatively contribute to a variety of diseases and, unlike mouse eosinophils, do not yet have an identified role in physiological health; thus, clarifying all roles of eosinophils remains an ongoing pursuit.

Interleukin 23 versus interleukin 12/23 inhibitors on preventing incidental psoriatic arthritis in patients with psoriasis? A real-world comparison from the TriNetX Global Collaborative Network.

BACKGROUND: Managing psoriasis and its comorbidities, particularly psoriatic arthritis, often involves using IL-23 and IL-12/23 inhibitors. However, the comparative risk of these treatments still needs to be explored. OBJECTIVE: This study evaluates the risk of developing psoriatic arthritis in patients treated with IL23 inhibitors compared to IL-12/23 inhibitors. METHODS: This retrospective cohort study utilized data from the TriNetX, including adult patients diagnosed with psoriasis. Patients with IL-23 or IL-12/23 inhibitors treatment were included and propensity score matched. The primary outcome was the incidence of arthropathic psoriasis, analyzed using a Cox regression hazard model and Kaplan-Meier estimates. RESULTS: The study included matched cohorts of patients treated with IL-23 inhibitors (n=2,273) and IL-12/23 inhibitors (n=2,995). Cox regression analysis revealed no significant difference in the cumulative incidence of arthropathic psoriasis between the IL-23i and IL-12/23i cohorts (p = 0.812). Kaplan-Meier estimates confirmed similar cumulative incidences of arthropathic psoriasis in both cohorts over the study period. LIMITATION: Long-term follow-up studies are required to understand more of the effects of these interleukin inhibitors. CONCLUSION: No significant difference but a numerically lower risk of PsA in PsO patients treated with IL-23 inhibitors than with IL-12/23 inhibitors, underscoring their comparable efficacy in PsO management and follow-up.

Posttransplant inflammatory bowel disease after successful solid organ transplantation: Not out of the woods yet.

OBJECTIVES: Gastrointestinal symptoms can occur following pediatric solid organ transplantation (SOT), and a subset of children will develop chronic inflammatory bowel disease (IBD) posttransplant. The goal of this study was to characterize patients who developed IBD following SOT, their treatment modalities, and clinical course. METHODS: A retrospective review was performed of electronic medical records of patients 0-18 years of age who underwent heart, kidney, liver, or intestinal transplantation at our center from January 2009 to April 2019. Patients who developed IBD were included in the final analysis. Demographics, symptoms, and clinical information were recorded. Endoscopic and histologic data and initial and current medications were noted for each patient. Outcomes of interest included phenotype at the time of IBD diagnosis, surgical interventions for IBD, and clinical trajectory at last median follow-up. RESULTS: Eight patients with IBD after heart (n = 3, 37.5%), kidney (n = 2, 25.0%), liver (n = 1, 12.5%), intestinal (n = 1, 12.5%), or multivisceral (heart and kidney, n = 1, 12.5%) transplants were included. Before IBD diagnosis, most patients developed diarrhea (n = 5, 62.5%) and abdominal pain (n = 5, 62.5%). Abnormal endoscopic findings were most common in the colon. Patients were started on medications including 5-aminosalicylates, steroids, and azathioprine. Two patients required biologic therapy and were receiving vedolizumab at last follow-up. Some patients required adjustment of immune suppression. CONCLUSIONS: Posttransplant IBD can occur following SOT. Patients exhibit inflammatory, nonstricturing disease though one patient experienced fistulizing disease. Complications are uncommon and many patients enter remission with 5-aminosalicylates alone, though some require adjustment in primary immune suppression.

Use of biologics in patients with psoriasis - A retrospective analysis based on real-world data.

OBJECTIVE: To summarize and analysis the application of biologic agents in patients with psoriasis in the real world. METHODS: Relying on collected data from June 2020 to September 2021 in the database of China Psoriasis Standardized Diagnosis and Treatment Center, 2529 cases of psoriasis patients treated with biologic agents in 188 different tertiary hospitals across China were retrospective analyzed. The collected information mainly includes demographic data (age, gender, psoriasis history), curative effectiveness of used biologics drug withdrawal and its reason. According to the collected information, condition of the usage for each category of biologics and influencing factor of biologics replacement were analyzed. RESULT: A total of 2529 patients were analyzed, which included 1626 male (64.29%) and 903 female (35.71%) with an average age of 42.12 ± 14.70 (17 âˆ¼ 85) years old; 2336 (92.37%) patients were aged from 19 to 60 years old. Within these patients, 2362 of them (93.40%) had a psoriasis area and severity index (PASI) score, and 1776 of these patients had moderate to severe cases (75.19%). According to the patient's self-evaluation of the past efficacy of biological agents, secukinumab was chosen by the most people to have the highest efficacy (1140 cases, 93.60%). The main reason for the withdrawal of secukinumab is that the disease is already well controlled at the time of withdrawal (67 cases, 38.95%); for TNF- α inhibitor is the poor curative effect; for ustekinumab and ixekizumab were the non-affordable price. CONCLUSIONS: In the current biotherapy of psoriasis in China, the efficacy of secukinumab is thought by most people to be the highest. Secukinumab is the first choice when the needs of changing biologics appear.

Treat-to-target vs fixed interval retreatment strategy with rituximab in rheumatoid arthritis: a retrospective cohort study.

To compare the effectiveness of retreatment of rheumatoid arthritis (RA) patients with rituximab (RTX) following the treat-to-target retreatment (TTr) or fixed interval retreatment (FIr) strategy. RA patients starting RTX treatment between January 2008 and June 2016, and receiving at least three infusion cycles were grouped by strategy (TTr, FIr or both). Primary outcome (between strategy difference in DAS28-CRP (Disease Activity Score in 28 joints calculated with C-reactive protein)) and secondary outcomes (flares, use of co-medication and mean yearly dose of RTX) were analyzed by group using linear mixed models to account for different strategies within patients. A total of 213 patients, 59 TTr (of whom 32 switched from TTr to FIr) and 186 FIr were included. No between-group difference in mean DAS28-CRP was found (0.10 DAS28-CRP point (95% CI - 0.07 to 0.26)). The TTr strategy did not result in more flares (IRR 1.13, 95%CI 0.87 to 1.47), conventional synthetic disease-modifying antirheumatic drug use (difference - 11.7%, 95%CI - 26.3% to 2.9%), or lower mean yearly RTX dose (difference 172 mg/yr, 95%CI - 355 to 11.7 mg/yr). RTX retreatment with either a TTr or FIr strategy does not seem to lead to better disease control and/or less drug use when used in a DAS28-CRP treat-to-target context. Choice of either strategy can, therefore, be made based on patient and physician preferences and logistical context.

Systemic Biologic Management of Atopic Dermatitis.

Dupilumab and tralokinumab are currently the only FDA-approved biologic therapies for the treatment of moderate-to-severe atopic dermatitis. Tralokinumab is approved for patients greater than 18 years old, and dupilumab is approved for patients as young as 6 months old. Both medications are effective in clinical trials at improving atopic dermatitis. With a good safety profile and low-risk adverse events, dupilumab and tralokinumab are generally excellent treatment options for patients with severe or refractory atopic dermatitis.

Safety and efficacy of biologic drugs in children or adolescents with atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials.

Children and adolescents suffering from moderate-to-severe atopic dermatitis (AD) face a significant disease burden that greatly impacts their quality of life. Treatment options for AD are currently limited. To assess the safety and efficacy of biologic drugs, dupilumab, lebrikizumab, or tralokinumab, in improving outcomes in patients with moderate to severe inadequately controlled AD. We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) comparing dupilumab, lebrikizumab or tralokinumab to placebo in patients with AD. We computed odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs), random effects model was used and a p-value <0.05 was considered as statistically significant. We analysed data into Review Manager 5.4. A total of five RCTs and 973 patients were included, of whom 592 were prescribed a biologic drug. Compared with placebo, patients receiving a biologic drug had a greater improvement, achieved an Investigator Global Assessment (IGA) score of 0 or 1 (OR 5.05; 95% CI 3.08-8.29), Eczema Area and Severity Index (EASI) 75 (OR 6.87; 95% CI 4.71-10.02), EASI 50 (OR 8.89; 95% CI 6.18-12.78) and EASI 90 (8.30; 95% CI 4.81-14.31). The proportion of patients with 3 points or more (OR 6.56; 95% CI 4.34-9.90) or 4 points or more (OR 8.09; 95% CI 5.19-12.59) improvement from baseline in peak pruritus NRS was significantly higher with biologic drugs than placebo. There were no significant differences between groups regarding adverse events (OR 0.79; 95% CI 0.58-1.07), and conjunctivitis (OR 2.08; 95% CI 1.00-4.33). In this meta-analysis, dupilumab, lebrikizumab, and tralokinumab have shown significant improvements in signs, symptoms and quality of life in children or adolescents with moderate to severe AD. Larger studies may be needed to continue evaluating the safety and efficacy of these biologic drugs in this patient population.

Pityriasis Rubra Pilaris: A Multicentric Case Series of 65 Spanish Patients. / [Artículo traducido] Pitiriasis rubra pilaris: serie de casos multicéntrica de 65 pacientes españoles.

INTRODUCTION: PRP is a rare entity of unknown etiopathogenesis. Lack of management guidelines makes it a challenge for clinicians. OBJECTIVE: To add our experience to increase evidence about PRP. METHODS: We performed a retrospective, descriptive and multicentric study of 65 patients with PRP, being the largest European case series of patients with PRP. RESULTS: PRP was more frequent in male patients with an average age of 51 years, but erythrodermic forms presented in older patients (average age 61 years). Six (75%) paediatric patients and ten (60%) non-erythrodermic adults controlled their disease with topical corticosteroids. On the contrary, 26 (68%) erythrodermic patients required biologic therapy as last and effective therapy line requiring an average of 6.5 months to achieve complete response. CONCLUSION: Our study showed a statistical difference in terms of outcome and response to treatment between children or patients with limited disease and patients who develop erythroderma.

Pityriasis Rubra Pilaris: A Multicentric Case Series of 65 Spanish Patients.

INTRODUCTION: PRP is a rare entity of unknown etiopathogenesis. Lack of management guidelines makes it a challenge for clinicians. OBJECTIVE: To add our experience to increase evidence about PRP. METHODS: We performed a retrospective, descriptive and multicentric study of 65 patients with PRP, being the largest European case series of patients with PRP. RESULTS: PRP was more frequent in male patients with an average age of 51 years, but erythrodermic forms presented in older patients (average age 61 years). Six (75%) paediatric patients and ten (60%) non-erythrodermic adults controlled their disease with topical corticosteroids. On the contrary, 26 (68%) erythrodermic patients required biologic therapy as last and effective therapy line requiring an average of 6.5 months to achieve complete response. CONCLUSION: Our study showed a statistical difference in terms of outcome and response to treatment between children or patients with limited disease and patients who develop erythroderma.

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.

An overview on the treatments and prevention against COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to plague the world. While COVID-19 is asymptomatic in most individuals, it can cause symptoms like pneumonia, ARDS (acute respiratory distress syndrome), and death in others. Although humans are currently being vaccinated with several COVID-19 candidate vaccines in many countries, however, the world still is relying on hygiene measures, social distancing, and approved drugs. RESULT: There are many potential therapeutic agents to pharmacologically fight COVID-19: antiviral molecules, recombinant soluble angiotensin-converting enzyme 2 (ACE2), monoclonal antibodies, vaccines, corticosteroids, interferon therapies, and herbal agents. By an understanding of the SARS-CoV-2 structure and its infection mechanisms, several vaccine candidates are under development and some are currently in various phases of clinical trials. CONCLUSION: This review describes potential therapeutic agents, including antiviral agents, biologic agents, anti-inflammatory agents, and herbal agents in the treatment of COVID-19 patients. In addition to reviewing the vaccine candidates that entered phases 4, 3, and 2/3 clinical trials, this review also discusses the various platforms that are used to develop the vaccine COVID-19.

Wound healing dynamics, morbidity, and complications of palatal soft-tissue harvesting.

Palatal-tissue harvesting is a routinely performed procedure in periodontal and peri-implant plastic surgery. Over the years, several surgical approaches have been attempted with the aim of obtaining autogenous soft-tissue grafts while minimizing patient morbidity, which is considered the most common drawback of palatal harvesting. At the same time, treatment errors during the procedure may increase not only postoperative discomfort or pain but also the risk of developing other complications, such as injury to the greater palatine artery, prolonged bleeding, wound/flap sloughing, necrosis, infection, and inadequate graft size or quality. This chapter described treatment errors and complications of palatal harvesting techniques, together with approaches for reducing patient morbidity and accelerating donor site wound healing. The role of biologic agents, photobiomodulation therapy, local and systemic factors, and genes implicated in palatal wound healing are also discussed.

Flares in Lupus Nephritis: Risk Factors and Strategies for Their Prevention.

PURPOSE OF REVIEW: Discuss the prognostic significance of kidney flares in patients with lupus nephritis, associated risk factors, and possible preventative strategies. RECENT FINDINGS: Recently performed clinical trials and observational cohort studies underscore the high frequency of relapses of kidney disease, following initial response, in patients with proliferative and/or membranous lupus nephritis. Analysis of hard disease outcomes such as progression to chronic kidney disease or end-stage kidney disease, coupled with histological findings from repeat kidney biopsy studies, have drawn attention to the importance of renal function preservation that should be pursued as early as lupus nephritis is diagnosed. In this respect, non-randomized and randomized evidence have suggested a number of factors associated with reduced risk of renal flares such as attaining a very low level of proteinuria (< 700-800 mg/24 h by 12 months), using mycophenolate over azathioprine, adding belimumab to standard therapy, maintaining immunosuppressive/biological treatment for at least 3 to 5 years, and using hydroxychloroquine. Other factors that warrant further clarification include serological activity and the use of repeat kidney biopsy to guide the intensity and duration of treatment in selected cases. The results from ongoing innovative studies integrating kidney histological and clinical outcomes, together with an expanding spectrum of therapies in lupus nephritis, are expected to facilitate individual medical care and long-term disease and patient prognosis.

Evaluation of hepatitis serology and frequency of viral reactivation in patients with inflammatory arthritis receiving biologic agents: a multicenter observational study.

To evaluate of hepatitis serology and reactivation frequency in patients with rheumatic disease receiving biologic agents. Our study included patients with inflammatory rheumatic diseases from 23 centers, who were followed up with biological therapy. Demographic and clinical characteristics of the patients, duration of drug use and hepatitis serology and the state of viral reactivation were analyzed. A total of 4060 patients, 2095 being males, were included in our study. Of the patients, 2463 had Ankylosing Spondylitis (AS), 1154 had Rheumatoid Arthritis (RA), 325 had Psoriatic Arthritis (PsA), and 118 had other inflammatory rheumatic diseases. When the viral serology of the patients was evaluated, 79 patients (2%) who were identified as HBs Ag positive, 486 (12%) patients who were HBs Ag negative and anti-HBc IgG positive and 20 patients (0.5%) who were anti-HCV positive. When evaluated on a disease-by-disease basis, the rate of HBsAg was found to be 2.5% in RA, 2% in AS and 0.9% in PsA. Viral reactivation was detected in 13 patients while receiving biologic agents. HBs Ag was positive in nine patients with reactivation and negative in four patients. Anti-HBc IgG, however, was positive. Six of these patients had AS, four had RA, and three had PsA. The development of hepatitis reactivation in 11.4% of HBs Ag positive patients and 0.82% of anti-HBc IgG positive patients due to the use of biologic agents is an important problem for this group of patients. Antiviral prophylaxis is recommended to be started especially in patients who are HBs Ag positive and who are using biologic agents due to viral reactivation. Therefore, it is important to carry out hepatitis screenings before biologic agent treatment and to carefully evaluate the vaccination and prophylaxis requirements.

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.

Incidence, Risk Factors, and Consequences of Human Alphaherpesvirus Infections in Patients With Psoriasis Who Initiate Methotrexate or Biologic Agents.

BACKGROUND: Immunosuppressive agents may increase the risk of infections with human alphaherpesviruses. METHODS: We included all adult patients with moderate to severe psoriasis who initiated methotrexate (MTX) or biologic agents in a retrospective cohort study. An episode of alphaherpesviruses infection was defined as filling a prescription for systemic acyclovir, valacyclovir, or famciclovir. Using nationwide registries, we determined the incidence, risk factors, 180-day hospital contacts, and 30-day mortality following infection. RESULTS: We included 7294 patients; 4978 (68%) received MTX, and 2316 (32%) biologic agents. The incidence rates (95% confidence intervals) of alphaherpesviruses were 23 (20-27), 26 (19-35), 17 (11-27), and 6.7 (1.3-21) per 1000 person-years of follow-up in patients on MTX, tumor necrosis factor alpha (TNF-α) inhibitors, interleukin 12/23 (IL-12/23) inhibitors, and interleukin 17 (IL-17) inhibitors, respectively. Males had an unadjusted hazard ratio (HR) of 0.47 (P < .001) for alphaherpesvirus infection. Patients on IL-17 inhibitors had an adjusted HR of 0.24 (P = .048) compared to TNF-α inhibitors. Within 180 days after infection, 13%, 7.5%, and <0.5% of patients on MTX, TNF-α inhibitors, and IL-12/23 or IL-17 inhibitors, respectively, had hospital contacts, and the 30-day mortality for all groups was <0.5%. CONCLUSIONS: The incidence and risk of alphaherpesvirus infections were comparable between patients on MTX and TNF-α inhibitors, whereas use of IL-17 inhibitors was associated with a lower risk.

New opportunities with biologic treatments in pediatric allergic and respiratory diseases.

In the last 20 years, the introduction of monoclonal antibodies has dramatically changed allergic diseases. At present, several monoclonal antibodies are approved for treating asthma, atopic dermatitis, chronic spontaneous urticaria, and chronic sinusitis with nasal polyps in children. Biologics have also changed the management of these diseases in the pediatric population, tending toward personalized medicine based on the type-2 inflammatory pattern.

Non-immune functions of inflammatory cytokines targeted by anti-psoriatic biologics: a review.

PURPOSE: Psoriasis is an inflammatory disease characterized by skin thickening with silvery white desquamation due to dysregulated inflammatory pathways and elevated levels of inflammatory cytokines. Biologic agents targeting these inflammatory cytokines have brought about significant improvement in clearing psoriatic lesions in patients with moderate-to-severe psoriasis. Moreover, biologics exert both beneficial and detrimental effects on comorbidities in psoriasis, which include increased risk of cardiovascular events, metabolic syndrome, among other conditions. However, non-immune functions of cytokines targeted by biologics, and, hence, the potential risks and benefits of biologics for psoriasis to different organs/systems and comorbidities, have not been well elucidated. RESULTS: This review summarizes current understanding of the pathogenesis of psoriasis-related comorbidities and emerging discoveries of roles of cytokines targeted in psoriasis treatment, including tumor necrosis factor α and interleukins 12, 23, and 17, aiming to complete the safety profile of each biologics and provide therapeutic implications on psoriasis-related comorbidities, and on diseases involving other organs or systems.

Severe asthma and COVID-19: lessons from the first wave.

OBJECTIVE: Severe asthma is considered a risk factor for SARS-Coronavirus 2 (SARS-CoV-2) infection but scientific evidences are lacking. METHODS: we performed a literature search and review based on PubMed database national, international recommendations as well as papers on severe asthmatic patients and their management during SARS-CoV-2 pandemic. RESULTS: the majority of international recommendations, expert panels and editorials provide indications about management of severe asthmatic patients. No published studies evaluated the effects of biologic agents on severe asthmatic patients during SARS-CoV-2 pandemic. CONCLUSIONS: the relationship between SARS-CoV-2 and asthma is variable worldwide and severe asthmatic patients were seldom reported in published cohorts. International recommendations suggest maintaining asthma under control to limit exacerbations occurrence, by using all available treatment. The minimum steroid dosage effective to control symptoms should be maintained to avoid exacerbations; biologic agents administration should be regularly scheduled encouraging patient support programmes.

Advancing Biologic Therapy for Refractory Autoimmune Hepatitis.

Biologic agents may satisfy an unmet clinical need for treatment of refractory autoimmune hepatitis. The goals of this review are to present the types and results of biologic therapy for refractory autoimmune hepatitis, indicate opportunities to improve and expand biologic treatment, and encourage comparative clinical trials. English abstracts were identified in PubMed by multiple search terms. Full-length articles were selected for review, and secondary and tertiary bibliographies were developed. Rituximab (monoclonal antibodies against CD20 on B cells), infliximab (monoclonal antibodies against tumor necrosis factor-alpha), low-dose recombinant interleukin 2 (regulatory T cell promoter), and belimumab (monoclonal antibodies against B cell activating factor) have induced laboratory improvement in small cohorts with refractory autoimmune hepatitis. Ianalumab (monoclonal antibodies against the receptor for B cell activating factor) is in clinical trial. These agents target critical pathogenic pathways, but they may also have serious side effects. Blockade of the B cell activating factor or its receptors may disrupt pivotal B and T cell responses, and recombinant interleukin 2 complexed with certain interleukin 2 antibodies may selectively expand the regulatory T cell population. A proliferation-inducing ligand that enhances T cell proliferation and survival is an unevaluated, potentially pivotal, therapeutic target. Fully human antibodies, expanded target options, improved targeting precision, more effective delivery systems, and biosimilar agents promise to improve efficacy, safety, and accessibility. In conclusion, biologic agents target key pathogenic pathways in autoimmune hepatitis, and early experiences in refractory disease encourage clarification of the preferred target, rigorous clinical trial, and comparative evaluations.