Pooled safety analysis of baricitinib in adult patients with atopic dermatitis from 8 randomized clinical trials. [(accessed on 17 November 2021)]. Ruxolitinib is an oral JAK inhibitor selective for JAK1 and JAK2 that is currently approved for myelofibrosis, polycythemia vera, and acute graft-versus-host disease.18 Like baricitinib, it can modulate downstream inflammatory responses via JAK1/JAK2 inhibition and has exhibited dose-dependent inhibition of IL-6-induced STAT3 phosphorylation.13 Ruxolitinib also has postulated antiviral effects by blocking SARS-CoV-2 from entering and infecting lung cells.14. conducted an extended safety analysis of baricitinib 2 mg by integrating results from phase II and phase III RCTs. 3401 Civic Center Blvd. Available at: Treon SP, Castillo JJ, Skarbnik AP, et al. Janus kinase inhibitors have been approved for use in or are currently under investigation for the treatment of: Atopic dermatitis. This research was supported by the Intramural Research Program of the NIH, NIAID, and NIAMS. Atopic dermatitis is the most prevalent chronic inflammatory skin condition in the word. For additional details on clinical trial data for baricitinib, see Table 6d. The .gov means its official.Federal government websites often end in .gov or .mil. [43], including 4-mg-treated arms in addition to the analysis of King et al. Abbreviations: PBO, placebo; IGA, investigator global assessment; W16, week 16; EoW, every other week; Dupi, dupilumab; bari, baricitinib. -, Arima K, et al. Monitoring safety and efficacy is important in benefit-risk assessment. JAKs are tyrosine protein kinases that play an important role in pro-inflammatory signaling pathways. Finally, the impact on therapeutic and economic management for the treatment of atopic dermatitis, following the approval of the new molecule, is discussed. The results showed a statistically significative difference between 4-mg therapeutic dosage regime and placebo in terms of efficacy, measured by two main primary endpoints among all of these trials: the percentage of patients achieving an IGA score 01 (with a 2-point or greater improvement from baseline) or an improvement of 75% of EASI score from baseline (EASI 75) [34,35,36,37]. Janus kinasis, by the Jak/STAT signaling, plays an important role in the immune and hematopoietic function, but it is also involved in the pathogenetic pathway of inflammatory diseases. Food and Drug Administration. Comprehensive review of JAK inhibitors in myeloproliferative neoplasms. Among the 33 cases reported, pregnancy outcomes were similar to those among the general population.21-23. Tofacitinib is a cytochrome P450 (CYP) 3A4 substrate. Patients who received 4 mg baricitinib achieved a significant improvement of at least 50% in EASI compared to patients who had received placebo (61% vs. 37%, respectively) at 16 weeks [34]. Baricitinib plus remdesivir for hospitalized adults with COVID-19. 2020 Oct;29(10):1089-1098. doi: 10.1080/13543784.2020.1800639. The primary endpoint Investigator global assessment (IGA) 01 was achieved by a significantly higher proportion of patients in the 4-mg and also in the 2-mg group compared to placebo (respectively, 16.4% (p < 0.001), 11.4% (p < 0.05), and 4.8% for AD1 and 13.8% (p = 0.001), 10.6% (p < 0.05), and 4.5% for AD2). Tofacitinib has less clinical data support than baricitinib, but tofacitinib can be used as an alternative if baricitinib is not available. This is particularly the case in patients who are current or past smokers, those with other cardiovascular risk factors, those who develop a malignancy, and those with a known malignancy other than a successfully treated nonmelanoma skin cancer. A search was conducted using PubMed/MEDLINE, Embase, Cochrane Skin databases, and Clinicaltrials.gov with the search terms atopic dermatitis or atopic eczema and baricitinib. Baricitinib is an oral JAK inhibitor discovered by Incyte and licensed to Lilly. Acalabrutinib (Calquence) [package insert]. Reich K., Kabashima K., Peris K., Silverberg J.I., Eichenfield L.F., Bieber T., Kaszuba A., Kolodsick J., Yang F.E., Gamalo M., et al. (b) Primary efficacy endpoint from BREEZE-AD1, AD2, AD4, AD5, and AD7: Proportion of patients treated with baricitinib 2 mg achieving IGA 01 at W16 compared to placebo. Further data are needed to evaluate long-term efficacy and safety in a real-life setting. Abbreviations: PBO, placebo; IGA, investigator global assessment; W16, week 16; Weidinger S., Beck L.A., Bieber T., Kabashima K., Irvine A.D. Atopic dermatitis. It is a type of leukodystrophy, a group of conditions that affect the white matter of the brain. From data available about safety, treatment-emergent Adverse Events (TEAEs) were reported in 54, 54, 58 and 58% of patients and in 56, 53, 58, and 54% of patients on placebo and baricitinib 1, 2, and 4 mg in BREEZE-AD1 and BREEZE-AD2, respectively. In preclinical studies of these treatments, preferential inhibition of specific JAKs (JAK1, JAK2, or JAK3) or the related tyrosine kinase 2 (TYK2) has been . {"type":"clinical-trial","attrs":{"text":"NCT03334422","term_id":"NCT03334422"}}NCT03334422, {"type":"clinical-trial","attrs":{"text":"NCT03334435","term_id":"NCT03334435"}}NCT03334435, {"type":"clinical-trial","attrs":{"text":"NCT03428100","term_id":"NCT03428100"}}NCT03428100, {"type":"clinical-trial","attrs":{"text":"NCT03435081","term_id":"NCT03435081"}}NCT03435081, {"type":"clinical-trial","attrs":{"text":"NCT03559270","term_id":"NCT03559270"}}NCT03559270, {"type":"clinical-trial","attrs":{"text":"NCT03733301","term_id":"NCT03733301"}}NCT03733301, {"type":"clinical-trial","attrs":{"text":"NCT03952559","term_id":"NCT03952559"}}NCT03952559. The frequency of SAE was low and similar to placebo. Data regarding ibrutinib are limited to those from an uncontrolled, retrospective case series of 6 patients with COVID-19 who received the drug for a condition other than COVID-19.28 The small sample size and lack of a control group limit evaluation of the data to discern any clinical benefit. The most common adverse events were upper respiratory infections, gastroenteritis, and BK viruria and viremia. In BREEZE-AD4, the primary endpoint was the percentage of participants achieving an EASI75 response at W16 from baseline. Healthcare (Basel). Ely EW, Ramanan AV, Kartman CE, et al. FDA expands ibrutinib indications to chronic GVHD. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE). JAK-STAT is also the intracellular signaling in Th2 cells that sustain the inflammatory loop by the activation and differentiation of the same Th2 and the innate immune cells and by the synthesis of pro-inflammatory cytokines IL-4 and IL-13, directed to keratinocytes, eosinophils, fibroblasts, and B lymphocytes. In particular, from AD studies the serum levels of IL-19, a pro-proliferative marker of keratinocytes, during treatment with baricitinib resulted to be closely related to EASI improvement [55,56]. the display of certain parts of an article in other eReaders. Abbreviations: PBO, placebo; IGA, investigator global assessment; W16. Cornez I., Yajnanarayana S.P., Wolf A.M., Wolf D. JAK/STAT disruption induces immuno-deficiency: Rationale for the development of JAK inhibitors as immunosuppressive drugs. Baricitinib in patients with moderate-to-severe atopic dermatitis: Results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5). Data from clinical trials are available about patients who tested positive for hepatitis C antibodies but negative for hepatitis C virus RNA and patients with surface antibodies and core hepatitis B antibodies, without hepatitis B surface antigen, who were allowed to receive the treatment [53]. For additional details on clinical trial data for tofacitinib, see Table 6d. Finally, baricitinib is currently under development to gain indication as treatment for alopecia areata in adult patients [49,50]. Currently, data available have shown the superiority of baricitinib in monotherapy (BREEZE-AD1, AD2, and AD5) or in association with TCS (Phase II, BREEZE-AD7, AD4) compared to placebo at week 16 of treatment. Several JAK inhibitors are under study for the approval on the treatment of atopic dermatitis, and baricitinib is the first to be approved [14]. Several articles have been published in the literature on efficacy and safety data obtained from the results of RCTs: the results are described below and summarized in Table 2. Baricitinib (LY3009104, INCB028050) is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays, ~70 and ~10-fold selective versus JAK3 and Tyk2, no inhibition to c-Met and Chk2. According to efficacy and safety results, the recommended dose of baricitinb in the treatment of AD is 4 mg once a day. Itch and Sleep Improvements with Baricitinib in Patients with Atopic Dermatitis: A Post-Hoc Analysis of 3 Phase 3 Studies. Oetjen L.K., Mack M.R., Feng J., Whelan T.M., Niu H., Guo C.J., Chen S., Trier A.M., Xu A.Z., Tripathi S.V., et al. A closer look at JAK/STAT signaling pathway. The burden of atopic dermatitis is extensive and reflects on quality of sleep, work productivity, emotional and mental health, physical activity, and social functioning of patients suffering from AD [45]. Baricitinib (Oliumiant) (Lilly) is a Janus Kinase inhibitor (JAK), specifically a JAK-1 and JAK-2 inhibitor. Persistence of atopic dermatitis(AD): A systematic review and meta-analysis. Janus kinase (JAK) inhibitors may be effective in blocking interferon activation in patients with the Aicardi-Goutires syndrome. doi: 10.1084/jem.20220759. ClinicalTrials.gov A Study of Baricitinib (LY3009104) in Adults with Severe or Very Severe Alopecia Areata (BRAVE-AA2). sharing sensitive information, make sure youre on a federal There are no clinical data on the use of zanubrutinib to treat COVID-19. Just as the growing knowledge of the multiple aspects of the pathogenesis of AD led to recognize new target molecules, future data could lead to a clinical laboratory correlation with the identification of specific biomarkers disease. However, since they share mechanisms of action with Xeljanz, FDA considers that these medicines may have similar risks as seen in the Xeljanz safety trial. Accessibility Darker shades indicate pretreatment, and lighter shades indicate the last included visit on baricitinib treatment. ( A ) Clinically significant improvement, Figure 5. A recent analysis of BREEZE-AD1, AD2, and AD7 focused on skin pain and quality of life improvement in patients treated with baricitinib. Epub 2022 Aug 23. A Janus kinase inhibitor, also known as JAK inhibitor or jakinib, [1] is a type of immune modulating medication, which inhibits the activity of one or more of the Janus kinase family of enzymes ( JAK1, JAK2, JAK3, TYK2 ), thereby interfering with the JAK-STAT signaling pathway in lymphocytes. 2018 Jul 21;392(10143):222-231. doi: 10.1016/S0140-6736(18)31363-1. Funding: Patients should seek emergency help right away if theyhave any symptoms that may signal a heart attack, stroke, or blood clot. American Society for Clinical Investigation. In BREEZE-AD7, among the 329 patients enrolled, the overall percentage of TEAEs was higher in the 4-mg (57.7%) and in the 2-mg baricitinib (56%) groups than placebo (38%). A small, single-blind, Phase 2 randomized controlled trial in patients with COVID-19 in China compared ruxolitinib 5 mg orally twice daily (n = 20) with placebo (administered as vitamin C 100 mg; n = 21), both given in combination with standard of care. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. [40]. Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial. doi: 10.1111/j.1749-6632.2011.06220.x. Results: Available at: McInnes IB, Byers NL, Higgs RE, et al. INDIANAPOLIS, Aug. 23, 2019 /PRNewswire/ -- Eli Lilly and Company (NYSE:LLY) and Incyte Corporation (NASDAQ:INCY) announced today that baricitinib met the primary endpoint in BREEZE-AD7, the third pivotal Phase 3 trial in the BREEZE-AD program to be completed in 2019.. BREEZE-AD7, an investigational study evaluating the efficacy and safety of baricitinib, an oral JAK inhibitor, to treat . Epub 2022 Sep 5. We are requiring new and updated warnings for two other. Moreover, JAK activation induces cell migration, differentiation, cell proliferation, and apoptosis. Boothe W.D., Tarbox J.A., Tarbox M.B. Background: In detail, grade 3 or 4 CPK elevations were seen in 1.6, 2.4, 3.3, and 2.4% of patients and in 2.1, 1.7, 1.7, and 4.9% of patients on placebo and baricitinib 1, 2, and 4 mg in BREEZE-AD1 and BREEZE-AD2, respectively. The second dataset included an additional two extension studies and examined the safety of baricitinib in all patients receiving at least one dose of baricitinib 2 mg: 1598 patients received once-daily baricitinib 2 mg for 1434.2 patient-years of exposure, for a maximum of 2.4 years, with a median time of 330 days. Improvement in longitudinal growth and hematologic parameters. Bieber T., Thyssen J.P., Reich K., Simpson E.L., Katoh N., Torrelo A., De Bruin-Weller M., Thaci D., Bissonnette R., Gooderham M., et al. Expanded access program overview and. Screening for viral hepatitis should be done in accordance with clinical guidelines prior to initiate therapy. JAK inhibitors have been proposed as a treatment option for COVID 19 because they can decrease the degree of immune activation and overall inflammation. The experimental program of baricitinb involved the identification of biomarkers for the evaluation of the therapeutic response, which are difficult to identify as per clinical practice. Epub 2021 Apr 15. The authors reported statistically significant improvements in itching and its impact on quality of life, sleep, and work activity in subjects treated with 4 mg + TCS compared with placebo + TCS starting at W1 and W2 of treatment. Sammaritano LR, Bermas BL, Chakravarty EE, et al. This study aims to investigate the clinical efficacy of baricitinib in patients with adult idiopathic inflammatory myositis (IIM). Conclusions: Following the efficacy and safety data on W 16 from the phase III BREEZE-AD studies, baricitinib has recently been approved in Europe for the treatment of moderate to severe AD in adult patients. 13 February 2017. Zhang W, Zhao Y, Zhang F, et al. [(accessed on 31 October 2021)]. The most frequently reported (2% in any treatment group) TEAEs for both baricitinib doses compared with placebo were nasopharyngitis, folliculitis, oral herpes, upper respiratory tract infection, acne, diarrhea, and back pain. Study duration, primary end-point, different dosage evaluated, and other main characteristics of the BREEZE AD program phase III studies are summarized in Table 1. 2015. Kim J.P., Chao L.X., Simpson E.L., Silverberg J.I. Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): a multicenter, single-blind, randomized controlled trial. A Review of Safety Outcomes from Clinical Trials of Baricitinib in Rheumatology, Dermatology and COVID-19. Investigating International Time Trends in the Incidence and Prevalence of Atopic Eczema 19902010: A Systematic Review of Epidemiological Studies. Topical delgocitinib, ruxolitinib, tofacitinib. Brutons tyrosine kinase (BTK) is a signaling molecule of the B-cell antigen receptor and cytokine receptor pathways. Oral tofacitinib, ruxolitinib, baricitinib. 2022. Acalabrutinib is a second-generation, oral BTK inhibitor that is FDA approved to treat B-cell malignancies (i.e., chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma). Previously, safety results from baricitinib in the treatment of AR [46] had raised the alert level for the occurrence serious of adverse events (malignancies, thrombosis, and serious infections) that did not occur in studies for AD, maybe due to the different disease-specific characteristics of study populations more than to the treatment with baricitinib. Authors reported that a greater proportion of patients treated with baricitinib reached at least a 4-point reduction in Skin Pain NRS score at week 16 in BREEZE-AD1 (baricitinib 4 mg 25.3%, p < 0.001), -AD2 (baricitinib 4 mg 20.0%, p < 0.001; baricitinib 2 mg 19.0%, p < 0.001), and -AD7 (baricitinib 4 mg 48.8%, p < 0.001; baricitinib 2 mg 45.2%, p = 0.004) compared to placebo. Several cases of creatinine phosphokinases elevation occurred according the CTCAE as grade 1 (14 and 23%) or grade 2 (7 and 6%) and few grade 3 (3 and 4%) and grade 4 (1 and 1%) of the 2- and 4-mg + TCS arms, respectively. Assessment of conventional inflammatory parameters (CRP) and IFN biomarkers (serum IP-10 levels and, MeSH This is a brief, descriptive literature review that describes the mechanism of action of the JAK inhibitors and their potential role in the treatment of atopic dermatitis, with a particular attention to baricitinib. doi: 10.1007/s00109-016-1465-5. Other competitors belonging to JAK inhibitors family (such as upadacitinib or abrocitinib) and monoclonal antibodies (anti IL-13 and anti IL-31) will be soon available. Improvement in longitudinal growth and. Baricitinib plus . (c) PROs endpoints from the BREEZE-AD1, AD2, AD4, and AD7: Change from Baseline to W16 in the in ADSS Item 2 in patients treated with baricitinib 4 mg compared to placebo. Zanubrutinib is a second-generation, oral BTK inhibitor that is FDA approved to treat mantle cell lymphoma.29 It has been shown to have fewer toxicities than first-generation BTK inhibitors (e.g., ibrutinib) because it has less off-target activity for other kinases.30 Zanubrutinib is proposed to benefit patients with COVID-19 by modulating signaling that promotes inflammation. Review of Bruton tyrosine kinase inhibitors for the treatment of relapsed or refractory mantle cell lymphoma. The proportion of patients who gained an EASI75 response at week 16 was significant in both 4-mg and 2-mg groups (48 and 43%, respectively) compared to placebo group (23%) [36]. (b) PROs endpoints from the BREEZE-AD1, AD2, AD4, and AD7: Change from Baseline to W16 in the Dermatology Life Quality Index (DLQI) in patients treated with baricitinib 4 mg compared to placebo. At week 16, the proportion of patients achieving the primary endpoint EASI75 was 8, 13, and 30% (p < 0.001, 2 mg vs. placebo), and those with a vIGA 01 were 5, 13, and 24% (p < 0.001, 2 mg vs. placebo) for placebo, baricitinib 1 mg, and baricitinib 2 mg, respectively [37]. Clinically important medical product safety alerts and timely information about the products you use, prescribe, or dispense every day. Based on the review of a large randomized safety clinical trial, theFDAhasconcluded there is an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with the arthritis and ulcerative colitis medicines Xeljanz and Xeljanz XR. Share sensitive information only on official, secure websites. Federal government websites often end in .gov or .mil. (a) Primary efficacy endpoint from BREEZE-AD1, AD2, AD4, and AD7: Proportion of patients treated with baricitinib 4 mg achieving IGA 01 at W16 compared to placebo. King et al. Tofacitinib (Xeljanz) [package insert]. doi: 10.1172/jci.insight.155250. But drug did not reduce disease progression in COV-BARRIER trial Treatment of hospitalized Covid-19 patients with the selective Janus kinase (JAK) inhibitor baricitinib, along with standard of care including dexamethasone, was associated with reduced mortality but not reduction in disease progression in the international, multicenter, phase III COV-BARRIER randomized trial. ClinicalTrials.gov NCT01724580 and NCT02974595. Calabrese L., Malvaso D., Chiricozzi A., Tambone S., DUrso D.F., Guerriero C., Peris K. Baricitinib: Therapeutic potential for moderate to severe atopic dermatitis. We conducted an open-label study of a single-center . Reich et al. It can modulate downstream inflammatory responses via JAK1/JAK2 inhibition and has exhibited dose-dependent inhibition of IL-6-induced STAT3 phosphorylation.13 Baricitinib has postulated antiviral effects by blocking SARS-CoV-2 from entering and infecting lung cells.14 In macaques infected with SARS-CoV-2, baricitinib reduced inflammation and lung pathology, but an antiviral effect was not confirmed.15. More delayed statistically significative improvements in patients treated with baricitinb 2 mg + TCS were observed starting from W4. Both treatment arms resulted in early benefits in HRQoL, symptom impact, and patient function across life domains that were sustained to week 16 and resulted in overall treatment benefit [39]. Publishers Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Finally, another phase III multicenter, randomized, double-blind, placebo-controlled, parallel-group, outpatient trial evaluating the pharmacokinetics, efficacy, and safety of baricitinib in pediatric patients with moderate to severe atopic dermatitis is now ongoing. J Clin Invest. However, the results of the indirect treatment comparison suggest that baricitinib is less effective than dupilumab. The STOP-COVID study examined the use of tofacitinib in people with COVID-19 pneumonia who were not receiving mechanical ventilation at the time of enrollment.11 The study demonstrated a survival benefit in patients who received tofacitinib, nearly all of whom also received corticosteroids. Abbreviations; PBO, placebo; TCS, topical corticosteroid; TEAE, treatment emergent adverse event; URIs, upper respiratory infections; CPK, creatine phosphokinase; SAE, serious adverse event; MACE, major adverse cardiovascular events; nr, not reported. Only the 2 patients who stayed in the study are shown. Hu X, Zhang H, Zhang Q, Yao X, Ni W, Zhou K. J Neuroinflammation. A growing body of literature has demonstrated that JAK inhibitors are safe and effective in multiple inflammatory skin conditions, extending the investigation of JAK inhibitors as a treatment for AD [23]. Monogenic IFN-mediated autoinflammatory diseases present in infancy with systemic inflammation, an IFN response gene signature, inflammatory organ damage, and high mortality. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: Results from two randomized monotherapy phaseIIItrials. If you are interested in learning more about the study, you may either submit our referral survey or contact the study team at agsclinicaltrials@email.chop.edu. J Am Acad Dermatol. King B., Maari C., Lain E., Silverberg J.I., Issa M., Holzwarth K., Brinker D., Cardillo T., Nunes F.P., Simpson E.L. Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from Eight Randomized Clinical Trials. You may notice problems with The https:// ensures that you are connecting to the Children and adolescents with atopic dermatitis (AD) were treated at different dosages of the JAK inhibitor and the high-dose group met the primary endpoint at week 16. Epub 2018 Feb 2. Clinical trial data on the use of JAK inhibitors, including baricitinib and tofacitinib, in patients with COVID-19 are summarized below and in Table 6d. Ali F., Vyas J., Finlay A. In animal studies, acalabrutinib and ibrutinib in doses exceeding the therapeutic human dose were associated with interference with embryofetal development.26,31 Based on these data, use of BTK inhibitors that occurs during organogenesis may be associated with fetal malformations. Further data to evaluate long-term efficacy and safety in a real-life setting are needed. JAK inhibitors in dermatology: The promise of a new drug class. 2-4. Baricitinib is an an oral JAK inhibitor first discovered by Incyte and licensed to Lilly. Abbreviations: PBO, placebo; DLQI, Dermatology Life Quality Index; W16, week 16; bari, baricitinib. The authors declare no conflict of interest. There were five reports of cancer other than non-melanoma skin cancer, two major adverse cardiovascular events, one peripheral venous thrombosis, one arterial thrombosis, and no pulmonary embolisms, deep vein thrombosis, or deaths [42]. Available at: RECOVERY Collaborative Group. Mahadevan U, Dubinsky MC, Su C, et al. (accessed on 2 November 2021). The efficacy of baricitinib 4 mg administered in monotherapy has been confirmed in both phase III trials BREEZE-AD1 and AD2 [35]. There is a paucity of data on human pregnancy and BTK inhibitor use. See this image and copyright information in PMC. Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from Eight Randomized Clinical Trials. Conclusion: 2018. [(accessed on 30 October 2021)]. -, Crow YJ. JAK-inhibitors are small-molecule inhibitors which may be manufactured in bulk quantity and administered orally. Encouraging results from the phase II randomized, double-blinded, placebo-controlled study have been reported about the efficacy of baricitinib in combination with topical corticosteroids in adult patients with moderate to severe AD at W16 [34]. Tofacitinib in patients hospitalized with COVID-19 pneumonia. Naldi L., Parazzini F., Gallus S. Prevalence of atopic dermatitis in Italian schoolchildren: Factors affecting its variation. Wollenberg A., Howell M.D., Guttman-Yassky E., Silverberg J.I., Kell C., Ranade K., Moate R., van der Merwe R. Treatment of atopic dermatitis with tralokinumab, an antiIL-13 mAb.