Biologics For Psoriasis Research Articles

14391 Emergent melanoma in patients being treated with biologics: Analysis of the Australasian Psoriasis Registry Peter Foley

Background: Psoriasis is a chronic inflammatory disease that is often treated with biologic agents. The association between current biologic agents used for psoriasis and melanoma risk is unclear. Methods We performed a retrospective analyses of the Australasian Psoriasis Registry (APR) dataset and reviewed the published safety data to look for any safety signal when it comes to biologics for psoriasis and melanoma.

Biologics in pediatric psoriasis and atopic dermatitis: revolutionizing the treatment landscape.

Biologics in pediatric psoriasis and atopic dermatitis: revolutionizing the treatment landscape.

Dermatologists on the medical need for therapeutic drug monitoring of biologics in psoriasis: results of a structured survey

Background Therapeutic drug monitoring (TDM) may lead to more rational use of biologics. Still, TDM is largely underexplored in psoriasis. Little is known about the dosing behavior of biologics by dermatologists, and their attitude toward TDM. Objective Exploration of the awareness and need for the concept of TDM in psoriasis amongst (inter)national dermatologists. Method A survey was distributed at the Belgian Dermatology Days 2019 and Skin Inflammation & Psoriasis International Network (SPIN) Congress 2019. Next, an online survey version was launched amongst the SPIN Scientific Committee members. We collected physician’s characteristics, prescription behavior of biologics, data regarding clinical response to biologics and attitude toward TDM. Results A total of 107 surveys were included for analysis. Most dermatologists were Belgium-based (54.2%), others from European (23.4%) or non-European countries (19.6%). Seventy percent performed either dose increase (64.8%), time interval shortening (74.6%), dose lowering (16.9%) or time interval extension (33.8%). The majority who performed dose adaptations acknowledged the need for TDM. Conclusion This study showed most dermatologists perform dose adaptations empirically. The need for TDM was indicated by the majority, implying the need for effective communication regarding availability, utility and implementation of TDM assays in daily dermatology practice.

Adjunctive Use of Calcipotriene/Betamethasone Dipropionate Foam in a Real-World Setting Curtails the Cost of Biologics Without Reducing Efficacy in Psoriasis

IntroductionAlthough the efficacy of monotherapy with biologics for psoriasis is well established, many patients fail to achieve complete plaque clearance from their initial biologic treatment alone. Adjunctive treatment with topical calcipotriene plus betamethasone dipropionate (Cal/BD) foam may offer substantial clinical benefit and potential cost savings.MethodsWe conducted a 16-week, open-label, single-arm study of adjunctive therapy with Cal/BD foam in subjects who had been treated with etanercept or adalimumab for ≥ 24 weeks but had not obtained a satisfactory treatment response. Assessments included affected body surface area (BSA), Physician’s Global Assessment (PGA) of disease severity, BSA × PGA, National Psoriasis Foundation (NPF) Treat to Target status, and likelihood of the physician to switch biologics. In parallel, a cost analysis was performed to compare the cost of switching to a different biologic versus adding Cal/BD foam to the original biologic.ResultsFour weeks of daily adjunctive treatment with Cal/BD foam led to notable reductions in BSA, PGA, and BSA × PGA relative to baseline. Additionally, by week 4, > 75% of subjects achieved NPF Treat to Target status, and the likelihood of the investigator to switch biologics decreased from 90.0% at baseline to 7.1%. The improved efficacy was maintained throughout the additional 12 weeks of maintenance Cal/BD foam application. The pharmacoeconomic evaluation demonstrated that adjuvant use of Cal/BD foam led to cost savings compared with switching biologic treatments.LimitationsDue to the nature of the open-label study lacking a vehicle-treated control, no statistical comparison can be made.ConclusionsThe results of this study demonstrate that the addition of Cal/BD foam to plaque psoriasis patients who still have significant disease activity despite being on stable biologic therapy improves treatment outcomes to the point where switching to a more expensive biologic therapy is a less suitable treatment option.

Comparing the efficacy and tolerability of biologic therapies in psoriasis: an updated network meta‐analysis

The rapid expansion of psoriasis biologics has led to an urgent need to understand their relative efficacy and tolerability to inform treatment decisions better and, specifically, to inform guideline development. To update a 2017 meta-analysis on the comparative efficacy and tolerability of biologic treatments for psoriasis. We searched the MEDLINE, PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs), published up to 7 September 2018, of 11 licensed, NICE-approved biologics targeting tumour necrosis factor (adalimumab, etanercept, infliximab, certolizumab pegol), interleukin (IL)-12/IL-23p40 (ustekinumab), IL-17A (secukinumab, ixekizumab), IL-17RA (brodalumab) and IL-23p19 (guselkumab, tildrakizumab, risankizumab). A frequentist network meta-analysis ascertained direct or indirect evidence comparing biologics with one another, methotrexate or placebo. This was combined with hierarchical cluster analyses to consider efficacy (≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) or Physician's Global Assessment 0 or 1; PASI 75; Dermatology Life Quality Index improvement) and tolerability (drug withdrawal due to adverse events) outcomes at 10-16 weeks, followed by assessments of study quality, heterogeneity and inconsistency. We identified 62 RCTs presenting data on direct comparisons (31 899 participants). All biologics were efficacious compared with placebo or methotrexate at 10-16 weeks. Hierarchical cluster analyses revealed that adalimumab, brodalumab, certolizumab pegol, guselkumab, risankizumab, secukinumab, tildrakizumab and ustekinumab were comparable with respect to high short-term efficacy and tolerability. Infliximab and ixekizumab clustered together, with high short-term efficacy but relatively lower tolerability than the other agents, although the number of drug withdrawal events across the network was low, so these findings should be treated with caution. Using our methodology we found that most biologics cluster together with respect to short-term efficacy and tolerability, and we did not identify any single agent as 'best'. These data need to be interpreted in the context of longer-term efficacy, effectiveness data, safety, posology and drug acquisition costs when making treatment decisions.

Meta-analysis results do not reflect the real safety of biologics in psoriasis.

In reported systematic reviews and meta-analyses of randomized controlled trials (RCTs) assessing treatments for psoriasis, the proportion of serious adverse events (SAEs) did not differ between treatments and placebo. Including cases of psoriasis worsening as SAEs may explain the lack of difference. This systematic review and meta-analysis aimed to explore this possibility. Among the 140 RCTs included in the Living Network Cochrane Review (last search on 8 May 2019), we selected those comparing a biologic treatment against placebo. The primary outcome was the numbers of SAEs in the treatment and placebo arms after excluding cases of psoriasis worsening. Secondary outcomes were the number of adverse events (AEs) of special interest. The trial was registered on PROSPERO (CRD42019124495). We analysed 51 RCTs. Of these, 21 included at least one anti-tumour necrosis factor (TNF)-α arm, 15 one anti-interleukin (IL)-17 arm, 11 one anti-IL-23 arm and nine one anti-IL-12/23 arm. With cases of psoriasis worsening included, the risk of occurrence of SAEs between biologic treatments and placebo did not differ: risk ratio (RR) 1·09, 95% confidence interval (CI) 0·88-1·36. After excluding cases of psoriasis worsening, the RR became significant (RR 1·30, 95% CI 1·02-1·65). By drug class, the RRs were for anti-TNF-α, 1·68 (95% CI 1·11-2·54; no missing data); anti-IL-17, 1·28 (95% CI 0·88-1·85; no missing data); anti-IL-23, 0·95 (95% CI 0·59-1·52; no missing data) and anti-IL-12/23, 1·18 (95% CI 0·72-1·94; no missing data). We were unable to examine potential differences in AEs of special interest between biologic treatments and placebo arms because of the small number of events. On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biologic than in the placebo arm. Given the rare events, we could not highlight whether this higher risk of SAEs was related to AEs of special interest. Reporting of SAEs in clinical trials has to be changed to provide more transparency through the separate reporting of disease flares leading to hospital admission and other SAEs.

Risk of COVID-19 in dermatologic patients receiving long-term immunomodulatory therapy

Risk of COVID-19 in dermatologic patients receiving long-term immunomodulatory therapy

Costs lower with apremilast than biologics for psoriasis

Costs lower with apremilast than biologics for psoriasis

Real-World Experience With Apremilast in the Treatment of Adults With Moderate to Severe Plaque Psoriasis in Québec: A Claims-Based Analysis of Drug Utilization and Healthcare Resource Utilization.

In Québec, targeted biologic therapies for moderate to severe plaque psoriasis are restricted to patients who have not responded to phototherapy or conventional systemic treatment, primarily due to high drug costs. Apremilast, an oral treatment for plaque psoriasis, was added to the Québec provincial health insurance plan (Régie de l'assurance maladie du Québec; RAMQ) formulary in 2015, making this the only province in Canada with public drug plan reimbursement for apremilast. The aim of this study is to describe patients' characteristics, treatment patterns, healthcare resource utilization (HCRU), and associated costs and to measure real-world budget impact of using apremilast before biologics in plaque psoriasis. This study was performed using RAMQ drug claims and medical services data. Patients diagnosed with psoriasis between January 2015 and December 2017 were identified. Medical services and prescription claims were categorized as all-cause and psoriasis-related. Using RAMQ database estimates, a 3-year budget impact analysis was developed comparing treatment cost with and without the addition of apremilast to the formulary. In all, 540 patients were identified (apremilast: n = 92; biologics: n = 448). Comorbidity burden and treatment persistence and adherence were comparable between apremilast and biologic users. The year following the index date, all-cause HCRU was lower for apremilast versus biologic users (CAN$19 763 vs CAN$28 025; P < .01), mainly driven by drug cost. Using apremilast before biologics resulted in an estimated RAMQ net savings of CAN$49 290 (2015), CAN$746 856 (2016), and CAN$1 216 512 (2017), and a total savings of CAN$2 012 658 since apremilast's addition to the formulary. Adding apremilast to the drug formulary of other Canadian provinces could result in significant healthcare savings.

Considerations for safety in the use of systemic medications for psoriasis and atopic dermatitis during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID‐19) is responsible for at least 2 546 527 cases and 175 812 deaths as of April 21, 2020. Psoriasis and atopic dermatitis (AD) are common, chronic, inflammatory skin conditions, with immune dysregulation as a shared mechanism; therefore, mainstays of treatment include systemic immunomodulating therapies. It is unknown whether these therapies are associated with increased COVID‐19 susceptibility or worse outcomes in infected patients. In this review, we discuss overall infection risks of nonbiologic and biologic systemic medications for psoriasis and AD and provide therapeutic recommendations. In summary, in patients with active infection, systemic conventional medications, the Janus kinase inhibitor tofacitinib, and biologics for psoriasis should be temporarily held until there is more data; in uninfected patients switching to safer alternatives should be considered. Interleukin (IL)‐17, IL‐12/23, and IL‐23 inhibitors are associated with low infection risk, with IL‐17 and IL‐23 favored over IL‐12/23 inhibitors. Pivotal trials and postmarketing data also suggest that IL‐17 and IL‐23 blockers are safer than tumor necrosis factor alpha blockers. Apremilast, acitretin, and dupilumab have favorable safety data and may be safely initiated and continued in uninfected patients. Without definitive COVID‐19 data, these recommendations may be useful in guiding treatment of psoriasis and AD patients during the COVID‐19 pandemic.

Biologics for psoriasis: what does drug survival tell us?

Linked Article:Yiu et al. Br J Dermatol 2020; 183:294–302.

The risk of respiratory tract infections and symptoms in psoriasis patients treated with interleukin 17 pathway–inhibiting biologics: A meta-estimate of pivotal trials relevant to decision making during the COVID-19 pandemic

To the Editor: Biologic agents have revolutionized psoriasis treatment.1Menter A. Strober B.E. Kaplan D.H. et al.Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.J Am Acad Dermatol. 2019; 80: 1029-1072Abstract Full Text Full Text PDF PubMed Scopus (364) Google Scholar However, they are considered “immunosuppressive,” and thus, safety assessments focus on infection, particularly those that are serious or opportunistic, or both. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has focused attention on respiratory track infections (RTIs).2Lebwohl M. Rivera-Oyola R. Murrell D.F. Should biologics for psoriasis be interrupted in the era of COVID-19?.J Am Acad Dermatol. 2020; 82: 1217-1218Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar The conceptual model of COVID-19 is that immunosuppression early in disease may be harmful, yet may be helpful in “late” severe COVID-19 illness; which may be mediated by a dysregulated hyperimmune response characterized by proinflammatory cytokines including interleukin 17 (IL-17).3Schett G. Sticherling M. Neurath M.F. COVID-19: risk for cytokine targeting in chronic inflammatory diseases?.Nat Rev Immunol. 2020; 20: 271-272Crossref PubMed Scopus (233) Google Scholar The effect of IL-17 inhibitors on COVID-19 is unknown, neither the risk of initial infection nor the risk of progression to worse disease. Current understanding of viral immunology suggests that IL-17 is not a dominant cytokine in viral immunity; however, IL-17 is important to mucosal immunity, raising the hypothesis that biologics targeting IL-17 could potentially increase RTI risk.4Das S. Khader S. Yin and yang of interleukin-17 in host immunity to infection.F1000Res. 2017; 6: 741Crossref PubMed Scopus (53) Google Scholar To test this hypothesis, we calculated a meta-estimate from the placebo-controlled period of phase 3 pivotal IL-17 trials of terms consistent with RTI of secukinumab, ixekizumab, and brodalumab abstracted from United States Food and Drug Administration prescribing information. RTI is a broad term classified by clinical judgment. The Medical Dictionary for Regulatory Activities (MedDRA), used to classify adverse events (AEs), has multiple terms for RTIs. To assess for RTIs, we summed the number of AEs that are associated with RTIs, divided by the total number of subjects in each study, and then calculated a meta-estimate. We found an increased risk of RTIs in the groups receiving IL-17 inhibitors compared with placebo (odds ratio, 1.56; 95% confidence interval, 1.04-2.33; Fig 1). Because prescribing information is not inclusive of all respiratory AEs from the pivotal trials that supported approval of IL-17 inhibitors, we conducted a summary risk estimate using data from the placebo-controlled period of these studies obtained from clinicaltrials.gov. This more detailed analysis yielded similar findings to our meta-estimate of prescribing information data (odds ratio, 1.31; 95% confidence interval, 1.05-1.62; Fig 2). Sensitivity analyses varying the terms analyzed yielded similar findings but with loss of statistical significance. Evaluating the risk of RTI in clinical trials is difficult because the diagnosis is made clinically without objective testing, and therefore, the etiology of these symptoms, be they viral, bacterial, fungal, or allergic, is unknown. Furthermore, there is substantial variation in the rates of RTIs in the placebo groups across the trials, demonstrating a lack of precision in measuring this outcome. For example, rates of “upper RTI” ranged from 0.0% to 7.44% in the placebo groups evaluated. In addition, owing to variation in reporting of MedDRA terms, the events were unevenly pooled because terms are reported inconsistently. It is also possible that patients may have had more than one RTI event, which could impact our estimates. These findings highlight the need for more meticulous evaluation of the impact of IL-17 inhibitors on RTIs in the setting of the novel coronavirus pandemic. Nevertheless, our meta-estimate demonstrates a potential safety signal for RTI associated with IL-17 inhibition and supports guidance issued by American Academy of Dermatology that clinicians should use their clinical judgment to continue or discontinue patients on these drugs in patients who have not tested positive or exhibited symptoms of COVID-19 and to discontinue these agents in patients who test positive for COVID-19 symptoms.5American Academy of Dermatology AssociationGuidance on the use of immunosuppressive agents.https://www.aad.org/member/practice/coronavirus/clinical-guidance/biologicsDate accessed: April 24, 2020Google Scholar Reply to research letterJournal of the American Academy of DermatologyVol. 83Issue 6PreviewTo the Editor: In light of the current coronavirus disease 2019 (COVID-19) pandemic, scientists have debated the safety of immunosuppressive biologic therapies. We read with interest the letter by Wan et al,1 “The risk of respiratory tract infections and symptoms in psoriasis patients treated with interleukin 17-pathway inhibiting biologics: A meta-estimate of pivotal trials relevant to decision-making during the COVID-19 pandemic.” We agree that caution should be used when exposing patients to systemic biologic agents in the setting of not only COVID-19 but also any acute or chronic infection, as Kaushik and Lebwohl2 have previously emphasized. Full-Text PDF

COVID-19 and biologics for psoriasis: A high-epidemic area experience—Bergamo, Lombardy, Italy

To the Editor: A severe outbreak of coronavirus disease 2019 (COVID-19) emerged in China in December 2019 and has rapidly spread worldwide. A large number of people in Italy have been infected with COVID-19, and it has become a serious public health emergency.1 The first case in our hospital was identified on February 21, 2020.2

Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biologic treatment and renal transplant recipients in maintenance immunosuppressive treatment

Risk of hospitalization and death from COVID-19 infection in patients with chronic plaque psoriasis receiving a biologic treatment and renal transplant recipients in maintenance immunosuppressive treatment

Sustainability and switching of biologics for psoriasis

&lt;p class="abstract"&gt;&lt;strong&gt;Background:&lt;/strong&gt; The optimal treatment guidelines for psoriasis using biologics are limited. In addition to this, the administration of the original biologic may be terminated or switched to another biologic due to inefficacy, adverse effects, and economic burden. Our objective is to compare demographic characteristics between switched and non-switched groups and to identify the reason for switching among various original biologics in our setup.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Methods:&lt;/strong&gt; We performed a retrospective cohort analysis of psoriatic patients on biologic treatment. Our analysis involved 42 patients, of which 19 were switched to the second biologic. The demographic characteristics and reason for biologic switching were noted and data analyzed between switched and non-switched groups.&lt;strong&gt;&lt;/strong&gt;&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Results:&lt;/strong&gt; First line therapies were infliximab (IFX, n=10), etanercept (ETN, n=21), secukinumab (SEC, n=11) and switching required in 3 (30%), 11 (52%), 5 (45%) patients respectively. The reason for switching, in general, in our setup is inefficacy (n=10; 53%), non-availability (n=8; 42%) and adverse event (n=1; 5%). Small number of patients, single-centre study and retrospective design were the limitations.&lt;/p&gt;&lt;p class="abstract"&gt;&lt;strong&gt;Conclusions:&lt;/strong&gt; Infliximab showed the least tendency to switch to the second biologic, however, it had adverse reactions. Inefficacy is the primary cause of switching. To the best of our knowledge, our study on Biologics switching is the first of its kind in the Indian scenario.&lt;/p&gt;

Novel Coronavirus Disease (COVID-19) and Biologic Therapy in Psoriasis: Infection Risk and Patient Counseling in Uncertain Times.

With the emergence of the novel coronavirus disease (COVID-19) viral pandemic, there is uncertainty whether biologic agents for psoriasis may place patients at a higher risk for infection or more severe disease course. This commentary offers patient counseling recommendations based on the current available evidence. While there are currently no specific data for psoriasis biologics and COVID-19, data are presented here from phase III clinical trials of psoriasis biologics on rates of upper respiratory infection, influenza, and serious infection. Overall these data reveal that on the whole, psoriasis biologics do not show major increases in infection risk compared to placebo during the course of these trials. However, as the COVID-19 virus is a novel pathogen that is associated with mortality in a subset of patients, a cautious approach is warranted. We discuss factors that may alter the benefit–risk ratio of biologic use during this time of COVID-19 outbreak. Ultimately, treatment decisions should be made on the basis of dialogue between patient and provider, considering each patient’s individualized situation. Once this pandemic has passed, it is only a matter of time before a new viral disease reignites the same issues discussed here.

Efficacy and safety of TNF blockers and of ustekinumab in palmoplantar pustulosis and in acrodermatitis continua of Hallopeau.

Palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH) are rare variants of psoriasis. Knowledge of the efficacy of biologics is scarce. To evaluate the real-life efficacy of tumour necrosis factor blockers and ustekinumab in PPP and in ACH. A multicentre retrospective descriptive study was conducted in 19 dermatology departments, including all patients with PPP or ACH seen from 2014 to 2016 who received one of the studied biologics. The data were collected by a standardized document. Factors associated with complete clearance (CC) were analysed by multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Among 92 patients included, 50 received adalimumab, 44 ustekinumab, 36 etanercept and 31 infliximab. Improvement and CC were observed in 83.9% and 20.0% patients receiving infliximab, 75.0% and 38.6% ustekinumab, 57.1% and 20.0% etanercept and 60.4% and 29.2% adalimumab. We found no significant difference in CC rates or duration of treatment among the biological treatments (P=0.18 and P=0.10, respectively). On multivariate analysis, CC with etanercept was associated with the ACH form and not smoking [OR=9.5 (95% CI 1.1-82.7), P=0.04 and 0.1 (0.01-0.9), P=0.04]; with ustekinumab, male sex and absence of obesity [6.0 (1.3-28.6), P=0.02 and 4.7 (1.0-22.7), P=0.05]; with adalimumab, the ACH form [11.9 (2.7-52.3), P=0.001]; and with infliximab, obesity [5.6 (1.1-29.4), P=0.04]. We found no difference in efficacy between TNF blockers and ustekinumab and among the three different TNF blockers in real life for PPP or ACH, which reveals the heterogeneity of clinical response to biologics in pustular psoriasis as compared with plaque psoriasis.

Should biologics for psoriasis be interrupted in the era of COVID-19?

To the Editor: With daily media warnings of a looming pandemic, physicians are understandably concerned about immunosuppressive or immunomodulating effects that might render patients receiving biologic therapies more susceptible to COVID-19 infection. At this early stage, we do not have specific data about susceptibility to the virus, but we have data on infectious complications for biologic therapies from their pivotal trials for psoriasis.

Efficacy and Safety of Biologics for Psoriasis and Psoriatic Arthritis and Their Impact on Comorbidities: A Literature Review

Psoriasis is a chronic inflammatory skin disease characterized by scaly indurated erythema. It impairs patients’ quality of life enormously. It has been recognized not only as a skin disease but as a systemic disease, since it also causes arthritis (psoriatic arthritis) and mental disorders. Furthermore, an association with cardiovascular events is indicated. With the advent of biologics, treatment of psoriasis dramatically changed due to its high efficacy and tolerable safety. A variety of biologic agents are available for the treatment of psoriasis nowadays. However, characteristics such as rapidity of onset, long-term efficacy, safety profile, and effects on comorbidities are different. Better understanding of those characteristic leads to the right choice for individual patients, resulting in higher persistence, longer drug survival, higher patient satisfaction, and minimizing the disease impact of psoriasis. In this paper, we focus on the efficacy and safety profile of biologics in psoriasis patients, including plaque psoriasis and psoriatic arthritis. In addition, we discuss the impact of biologics on comorbidities caused by psoriasis.

Phenotypic switch to eczema in patients receiving biologics for plaque psoriasis: a systematic review.

The use of biologic therapies for the treatment of chronic plaque psoriasis has been linked to the development of atopic eczema, amongst other cutaneous adverse events. This can cause diagnostic confusion and create difficulty in the management of patients with plaque psoriasis. The main objective of this systematic review was to review all cases of eczema, including atopic eczema, reported in patients treated with biologics for chronic plaque psoriasis. PubMed, Medline and Embase databases were used to identify studies reporting eczema in patients treated with biologic therapy for chronic plaque psoriasis. A total of 92 patients were identified from 24 studies, with patients treated with either: adalimumab; etanercept; infliximab; ixekizumab; secukinumab; or ustekinumab. Factors common to some reported cases include: a prior history of atopy; eosinophilia; raised serum immunoglobulin E. Twenty-three had documented treatment outcomes; 14 had biologic therapy discontinued or switched. Management strategies included topical or oral corticosteroids, and treatment with alternative systemic agents such as ciclosporin or apremilast. This adverse event occurred in 1.0-12.1% of patients within trial data and observational studies. This review demonstrates that there are consistent reports of a switch to an atopic eczema phenotype from psoriasis in patients taking biologics inhibiting tumour necrosis factor alpha and the interleukin (IL)-17/IL-23 axis. The majority stopped the implicated biologic, but conservative management was successful in some cases. Those with an atopic diathesis may be more at risk. Elucidation of mechanisms and risk factors would contribute to optimal therapy selection for individual patients.