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222 Textbook of Diagnostic and Therapeutic Procedures in Allergy
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Safety Data
In a systematic review, there were no significant differences in the frequency of adverse events
(AE) between omalizumab and placebo, with most as mild to moderate in severity (Rodrigo et al.
2011). The most commonly reported AEs included nasopharyngitis, upper respiratory tract infection
(URTI) and headache. Anaphylaxis, although a rare AE, has been reported in premarketing trials as
well as post-marketing reports, with rates of 0.1–0.2% (Lieberman et al. 2017). Initial reports from
RCTs prompted concern for malignancy associated with omalizumab use, the phase 4 EXCELS trial
refuted this claim (Long et al. 2014). However, omalizumab was found to have a higher incidence
rate of cardiovascular (CV)/cerebrovascular (CBV) serious AEs, though authors postulated this may
be due to an imbalance in baseline asthma severity. This requires further investigation (Iribarren
et al. 2017).
Uncontrolled asthma during pregnancy can increase the risk for adverse outcomes, including
perinatal mortality, congenital anomalies, preterm birth as well as adverse maternal outcomes.
Unfortunately, for many asthma medications, particularly biologics, pregnancy safety data is
lacking. The omalizumab pregnancy registry, EXPECT, evaluated maternal, pregnancy and
infant outcomes after exposure to omalizumab (Namazy et al. 2015). When compared to a
disease-matched population of pregnant women not treated with omalizumab, there were similar
rates of live births with no apparent increase in miscarriage or major congenital anomalies among
women in both cohorts (Namazy et al. 2020). There was a slightly increased rate of low birth weight
among infants exposed to omalizumab, although the investigators postulated this may have been
driven by differences in underlying disease severity along with the increased prevalence of baseline
comorbidities, like obesity.
Omalizumab Key Points
• Omalizumab is effective in adults and children with allergic asthma. It reduces seasonal asthma
exacerbations along with respiratory virus exacerbations, particularly rhinovirus.
• Based on available data, there are no reliable biomarkers for predicting the response of
omalizumab.
• Omalizumab has a favorable safety profile with a rare risk of anaphylaxis. There is no increased
risk of malignancy, although there is a higher incidence rate of CV/CBV events in patients
treated with omalizumab compared with the disease-matched cohort.
• Pregnancy safety data for omalizumab demonstrated no maternal deaths and no apparent
increase in miscarriage and/or major congenital malformations, although there was a slight
increased rate of low birthweight among infants exposed to omalizumab. As such, the decision
to continue omalizumab during pregnancy should be individualized and based upon shared
decision-making with the patient after a thorough discussion of risks and benefits.
Anti-Interleukin (IL)-5/5 Receptor (R)
IL-5 is the primary cytokine responsible for eosinophil production, activation and survival. Thus,
disruption of the IL-5 receptor decreases eosinophils throughout the body (Kolbeck et al. 2010).
Reslizumab
Reslizumab is a humanized anti-IL-5 antibody (IgG4 kappa), FDA approved in 2016 for add-on
maintenance therapy of severe eosinophilic asthma (SEA) in patients ages 18 years and older.
Reslizumab is currently the only weight-based and IV anti-IL-5 asthma biologic therapy.
Efficacy Data
In duplicate, multicenter phase 3 RCTs, patients with uncontrolled eosinophilic asthma treated with
reslizumab had significant reductions in the frequency of asthma exacerbations compared to placebo
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(Castro et al. 2015). These findings were accompanied by significant improvements in lung function
(FEV1), BEC and in patient-reported outcomes (PROs), including the asthma control questionnaire
(ACQ) and asthma quality of life questionnaire. In various posthoc analyses, reslizumab also
demonstrated efficacy in specific asthma cohorts; those with chronic rhinosinusitis with nasal
polyps (CRSwNP) with or without aspirin sensitivity (Weinstein et al. 2019), late-onset asthma
(Brusselle et al. 2017), OCS dependency (Nair et al. 2020) as well as multiple prior exacerbations
within the past year (Wechsler et al. 2020). Notably, reslizumab was not found to be effective when
administered to asthma patients unselected for eosinophil count (Corren et al. 2016).
The efficacy of reslizumab for the treatment of uncontrolled SEA has been confirmed in an
open-label extension (OLE) and several real-world studies following FDA approval. In an OLE
study of several phase 3 trials, reslizumab maintained improved lung function and asthma control
in patients with moderate-to-SEA throughout the follow-up period of up to 3 years (Murphy
et al. 2017). In a real-world study, patients sustained similar improvements along with a decreased
frequency of asthma exacerbations throughout their treatment with reslizumab (Wechsler
et al. 2021a).
Safety Data
In a pooled safety analysis, reslizumab demonstrated a favorable safety profile of long-term
treatment, which was similar to the placebo. The most common AEs were asthma, nasopharyngitis
and URTIs. There were three cases of anaphylaxis due to reslizumab infusion (Virchow et al. 2020).
Mepolizumab
Mepolizumab is an IL-5 receptor alpha monoclonal antibody (IgG1; kappa) FDA approved in 2015
for add-on maintenance therapy for patients 6 years of age or older with SEA.
Efficacy Data
In the MENSA phase 3 RCT, treatment with mepolizumab led to a significant reduction in
exacerbations compared with placebo as well as significant improvements in lung function (FEV1),
asthma symptoms and QoL (Ortega 2014). In the SIRIUS phase 3 RCT (Bel 2014), treatment with
mepolizumab led to a significantly higher likelihood of OCS reduction as well as a reduction in
asthma exacerbations despite OCS reduction. Mepolizumab’s efficacy was sustained for up to
152 weeks, with improvements in exacerbations, asthma symptoms, lung function and OCS dose in
the COSMEX OLE study (Khurana et al. 2019).
Real-World Studies
Various real-world studies further reinforce the efficacy of mepolizumab as an effective therapeutic
agent in the treatment of SEA, which concluded that mepolizumab was associated with reduced
exacerbations, including those requiring hospitalizations or ER presentations, decreased median
daily OCS doses and improvement in lung function and QoL (Harrison et al. 2020).
Other Disease Considerations
In addition to various FDA-approved indications, mepolizumab is also being investigated as a
treatment option for COPD, with promising results thus far although further studies are warranted to
confirm its efficacy (Isoyama et al. 2021). Smaller case reports have been reported on the potential
efficacy of mepolizumab, via off-label use, in the treatment of ABPA (Schleich et al. 2020) as well
as Chronic Eosinophilic Pneumonia (CEP) (Bernard et al. 2020).
Safety Data
Mepolizumab demonstrated a favorable safety profile with the most frequently observed AEs reported
as URTI, headache, worsening asthma and bronchitis. Serious AEs attributed to mepolizumab were
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rare with no episodes of anaphylaxis noted (Khatri et al. 2019). Rarely, mepolizumab therapy has
been linked to opportunistic infections, including herpes zoster and helminth infections.
Benralizumab
Benralizumab is an anti-IL-5 receptor alpha monoclonal antibody (IgG1; kappa); FDA approved in
2017 for add-on maintenance therapy for patients 12 years or older with SEA.
Efficacy Data
In the CALIMA and SIROCCO phase 3 RCTs, benralizumab was associated with significantly lower
annual exacerbation rates as well as improved lung function (pre-bronchodilator FEV1) (FitzGerald
et al. 2016; Bleecker et al. 2016). In addition, treatment with benralizumab had significant
improvement in all PROs, including rescue medication use, activity limitation and nighttime
awakenings, with effects as early as day 1 (O’Quinn et al. 2019). Of importance, benralizumab’s
efficacy was maintained irrespective of baseline serum IgE level or atopy status (Chipps et al.
2018). Treatment with benralizumab led to a higher median reduction of OCS from baseline with
higher odds of discontinuation as compared to placebo in the ZONDA trial (Nair et al. 2017). In a
preliminary press release, treatment with benralizumab enabled 91% of patients to eliminate OCS or
reduce their dose to ≤ 5 mg per day, with responses sustained for at least six months (“AstraZeneca,
unpublished data”). The benefits of benralizumab were maintained throughout long-term use
over 2 years with 50% of patients experiencing zero exacerbations during this period (FitzGerald
et al. 2019).
Real-World Studies
Many real-world studies further demonstrate the efficacy and safety of benralizumab as an add-on
therapy in SEA. In one study, benralizumab was associated with a significant depletion of BEC,
reduction of asthma exacerbations, lung function (FEV1), improvement in asthma symptoms and
decrease in prednisone dose (from 25 to 0 mg) (Pelaia et al. 2020). These results were corroborated
in a retrospective observational study with 95% of patients being able to suspend OCS use (Menzella
et al. 2020).
Other Disease Considerations
Several case reports have reported the potential efficacy of off-label use of benralizumab in ABPA
(Tomomatsu et al. 2020) and CEP (Isomoto et al. 2020).
Safety Data
Benralizumb has a favorable safety profile, with similar rates of AEs between treatment and placebo
groups. Common AEs associated with benralizumab use include viral URTIs and worsening asthma,
with rare reports of serious AEs (worsening asthma; pneumonia) (Busse et al. 2019).
Anti-IL5/5R Key Points
• There are currently three anti-IL5/5R biologics indicated for the treatment of SEA, reslizumab,
mepolizumab and benralizumab. Mepolizumab is also FDA-approved for the treatment of
CRSwNP, hypereosinophilic syndrome (HES) and eosinophilic granulomatosis polyangiitis
(EGPA).
• The anti-IL5/5R biologics are efficacious, in terms of exacerbation reduction, FEV1
improvement, and OCS reduction with an acceptable safety profile in the treatment of SEA in
children and adults.
• Long-term safety data for these medications are reassuring. While rare, there were reports of
herpes zoster infections with mepolizumab and therefore if indicated, based upon risk factors
and age, consider vaccination for herpes zoster prior to initiation of mepolizumab treatment.
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Anti-IL-4/13
The IL-4 receptor axis interacts with IL-4 and IL-13 to promote T helper 2 (Th2) differentiation and
inflammation, ultimately leading to downstream effects in various end organs and the pathogenesis
of various allergic disorders (Harb and Chatila 2020).
Dupilumab
Dupilumab is a fully human monoclonal antibody to the IL-4 receptor alpha (α) subunit, which
inhibits both IL-4 and IL-13 signaling. It is indicated as an add-on maintenance treatment for ages
6 years and older with moderate-to-severe eosinophilic or OCS-dependent asthma.
Efficacy Data
In phase 3, LIBERTY ASTHMA QUEST RCT (Castro et al. 2018), dupilumab led to a significant
reduction in the rate of asthma exacerbations in adolescents and adults with uncontrolled asthma
along with significant and rapid improvement in lung function (FEV1) with its greatest benefit
among patients with baseline BEC of 300 cells/µL and FeNO 25 ppb.
In the LIBERTY ASTHMA VENTURE phase 3 RCT, dupilumab was found to be effective in
children and adults with OCS-dependent severe asthma, leading to a significant decrease in OCS
dose as well as increased likelihood of OCS discontinuation (Rabe et al. 2018), more pronounced in
patients with baseline BEC 300 cells/µL. Dupilumab treatment also led to lower annualized rates of
severe asthma exacerbations and higher FEV1 than placebo, both of which were more pronounced
in patients with higher baseline BEC and FeNO levels. Similar to prior studies, dupilumab treatment
led to a reduction in FeNO, as soon as by week two in this trial, which was sustained throughout
treatment.
Real-World Studies
RCT findings have been corroborated with real-world evidence. In a retrospective, real-world cohort
(Dupin et al. 2020), treatment of severe asthmatics with dupilumab led to significant improvement in
clinical outcomes, including asthma symptoms and lung function. Notably, the daily prednisone dose
significantly decreased from 20 to 5 mg and annual asthma exacerbations decreased from 4 to 1.
In another real-world, retrospective analysis (Mummler et al. 2021), switching to dupilumab in
patients with prior insufficient response to anti-IL-5/5R or anti-IgE therapies was found to benefit
most patients, with a significant increase in FEV1 and in Asthma Control Test (ACT) score. Half
of the OCS-dependent patients were able to taper their OCS dose by more than 50%. Those with
FeNO ≥ 25 ppb under prior therapy were more likely to be responders, although there were no
other characteristics that differentiated responders. In another real-world, retrospective analysis
(Bavaro et al. 2021), patients with aspirin-exacerbated respiratory disease (AERD) who previously
received anti-IL-5/5R therapy were treated with dupilumab, after which sinonasal PROs (Sinonasal
outcome test-22 (SNOT-22), smell/taste and congestion scores) significantly improved compared to
baseline and after anti-IL-5/5R treatment. Although there were no differences in FEV1, annualized
asthma exacerbation rate was significantly higher during treatment with anti-IL-5/5R compared
with dupilumab treatment.
Other Disease Considerations
In addition to FDA-approved indications, case reports have demonstrated dupilumab’s potential
efficacy, via off-label use, in the treatment of refractory ABPA (Mikura et al. 2021).
Safety Data
Dupilumab’s safety profile has been reported as acceptable and well-tolerated, with similar rates
of AEs in both the dupilumab and placebo groups (Rabe et al. 2018). The most frequent AEs were
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URTIs, bronchitis, sinusitis and influenza. Injection-site reactions were observed more frequently in
the dupilumab group compared with the placebo. Notably, no AEs of conjunctivitis were observed.
During a phase 2b trial (Wenzel et al. 2016) transient elevation of BECs in patients treated with
dupilumab was noted, particularly in those with higher baseline BECs. There was one report of
the development of HES in a patient with a known high baseline BEC. This phenomenon has been
repeatedly substantiated and has been attributed to dupilumab’s inhibition of eosinophil migration
into tissues via its interaction with IL-4 and IL-13. Fortunately, most cases are asymptomatic without
clinical consequences (Rabe et al. 2018; Castro et al. 2018).
Dupilumab Key Points
• Dupilumab is currently indicated as an add-on maintenance treatment for adult and pediatric
patients with moderate-to-severe eosinophilic or OCS-dependent asthma. It is currently only
asthma biologic approved for an indication of OCS-dependent asthma.
• Dupilumab has proven efficacious in the treatment of asthma, which is based upon clinical
trials and real-world studies, including in patients previously unresponsive to anti-IgE or
anti-IL-5/5R biologics.
• With regards to biomarkers, the benefit of dupilumab is found to be greater among patients with
baseline BEC of ≥ 300 cells/µL and FeNO ≥ 25 ppb as demonstrated in clinical trials.
• Dupilumab has an overall acceptable safety profile in the treatment of asthma. The increase in
BEC has shown to often be transient and asymptomatic.
Tralokinumab and Lebrikizumab
Given dupilumab’s efficacy in the treatment of asthma as well as IL-13’s prominent role within
the T2 pathway, anti-IL-13 monoclonal antibodies were of clinical interest in the treatment of
uncontrolled asthma. However, RCTs did not demonstrate significant clinical benefits of these
therapeutics, including tralokinumab (Panettieri et al. 2018) or lebrikizumab (Hanania et al. 2016).
Anti-Epithelial Cytokines
Tezepelumab
Thymic stromal lymphopoietin (TSLP) is a pleiotropic, epithelial cell-derived cytokine that is
involved in the initiation of several inflammatory cascades. TSLP has been implicated in a variety
of disorders, including allergic, autoimmune and chronic inflammatory disorders as well as several
malignancies (Varricchi et al. 2018). Levels of human TSLP are increased in the airways of patients
with asthma and correlate with disease severity (Li et al. 2018). Tezepelumab is an anti-TSLP human
IgG2 monoclonal antibody, FDA-approved in December 2021 for add-on maintenance treatment of
patients with severe asthma aged 12 years and older.
Efficacy Data
In the PATHWAY phase 2b trial, patients with severe, uncontrolled asthma treated with Tezepelumab
had 71% lower rates of asthma exacerbations when compared with placebo, independent of baseline
BEC. Additionally, Tezepelumab-reduced BEC, FeNO and total serum IgE levels across all groups
(Corren et al. 2017). Treatment with Tezepelumab led to clinically meaningful improvements in
asthma control, QoL and daily asthma symptoms (Corren et al. 2021b). Tezepelumb consistently
reduced exacerbation rates irrespective of perennial allergy status (Corren et al. 2021a). Additionally,
Tezepelumab reduced the rate of asthma exacerbations that required hospitalizations or ED
visits. Of those who did require hospital admission, they spent fewer mean days in the hospital
and/or ICU compared with those who received a placebo (Corren et al. 2020b). In the CASCADE
exploratory phase 2 trial, (Emson et al. 2020) treatment with Tezepelumab resulted in a significantly
greater reduction of airway submucosal eosinophils compared with placebo in patients with severe,
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uncontrolled asthma, irrespective of baseline BEC, with a corresponding reduction in T2 biomarkers
such as BEC, serum T2 cytokines and FeNO.
In the NAVIGATOR phase 3 trial, adolescent and adult patients with severe, uncontrolled
asthma treated with Tezepelumab experienced fewer exacerbations and had significantly improved
lung function, asthma control, and health-related QoL than those who received a placebo
(Menzies-Gow et al. 2021). Preliminary data from the ongoing SOURCE phase 3 trial, Tezepelumab
did not significantly reduce OCS dose compared with placebo in adults with OCS-dependent asthma;
however, full data has not yet been made publicly available (“AstraZeneca, unpublished data”).
Other Disease Considerations
Given its promising role in multiple inflammatory disorders, Tezepelumab is currently under
investigation for other disease considerations including severe CRSwNP, CSU, COPD as well as
eosinophilic esophagitis (EoE) (Kemp 2021). However, Tezepelumab was not found to be efficacious
in patients with severe atopic dermatitis (AD) (Simpson et al. 2019).
Safety Data
In phase 2 and phase 3 trials, the frequencies and types of AEs were similar between Tezepelumab
and placebo groups (Corren et al. 2017; Menzies-Gow et al. 2021). The most commonly reported
AEs were nasopharyngitis, URTI, headache, bronchitis and asthma.
Tezepelumab Key Points
• Tezepelumab is the most recently approved biologic for severe asthma and the only biologic
approved for asthma without phenotype or biomarker limitations.
• Tezepelumab has an overall favorable safety profile.
Anti-IL-33 and Anti-ST2
IL-33 is an epithelial-derived alarmin released in response to tissue injury. When IL-33 binds to
its receptor (ST2; IL-1 receptor-like 1), it initiates a downstream signaling cascade leading to T2
and non-T2 inflammation, which can contribute to airway disease. As such, it provides a potential
therapeutic option in the management of airway disease and recent phase 3 studies have shown
promising results.
Itepekimab is a new human IgG4P monoclonal antibody against IL-33. In a recent phase 2
trial, adults with moderate-to-severe asthma were randomized to receive SC itepekimab 300 mg,
itepekimab plus dupilumab (referred to as combination therapy), dupilumab or placebo (Wechsler
et al. 2021b). At the end of the trial, significantly fewer patients in the itepekimab and combination
groups experienced an event indicating loss of asthma control. Lung function (FEV1) increased with
itepekimab and dupilumab monotherapies but not with combination therapy. Although dupilumab
efficacy was generally greater than that observed with itepekimab, the trial was not powered to
compare these differences. The frequency of AEs was similar across treatment groups.
Astegolimab is a human IgG2 monoclonal antibody that blocks IL-33 signaling by selectively
inhibiting ST2, the IL-33 receptor. In the ZENYATTA Phase 2b trial (Kelsen et al. 2021), asthma
exacerbation rates were significantly improved relative to placebo in the astegolimab 70 mg and
490 mg groups, although not significant at the 210 mg dose. When adjusted for BEC < 300 cells/μL,
results were comparable to the overall population. AEs were similar in astegolimab and
placebo groups.
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Asthma Key Points
• Although there are several biologics approved for the treatment of asthma, head-to-head
comparator trials are lacking. See Table 1 for a comparison between available trial data.
• The decision to prescribe a biologic should be individualized with consideration of clinical
characteristics and comorbidities, biomarkers, potential adverse effects as well as patient
preferences.
Atopic Dermatitis
Atopic dermatitis (AD) is an inflammatory skin disease affecting both children and adults and is
characterized by recurrent pruritus and eczematous lesions (Ratchataswan et al. 2021). Its treatment
can often be challenging, although the recent development of various biologics as well as Janus
Kinase (JAK) inhibitors has provided significant benefit in this population as seen in Tables 2 and 3.
Anti-IL 4/13 Therapeutics
Dupilumab
Dupilumab is indicated for the treatment of adult and pediatric patients ages 6 years and older with
moderate-to-severe AD that is inadequately controlled with topical prescription therapies or when
those therapies are not advisable.
Efficacy Data
In dual-phase 3 RCTs, SOLO 1 and SOLO 2, significantly more patients with moderate-tosevere AD treated with dupilumab monotherapy achieved an Investigator’s Global Assessment
score of 0/1 (IGA 0/1) and EASI75 (Eczema Area and Severity Index with > 75% improvement)
compared with placebo (Simpson et al. 2016). Dupilumab also significantly improved pruritus and
QoL. These results were corroborated in the adolescent population in the LIBERTY AD ADOL
phase 3 RCT (Simpson et al. 2020a). Additionally, dupilumab therapy with concomitant topical
corticosteroids (TCS) was proven to be efficacious in the adult and pediatric populations in the
phase 3 LIBERTY AD CHRONOS (Blauvelt et al. 2017) and LIBERTY AD PEDS RCTs (Paller
et al. 2020), respectively, as well as in adults with inadequate response to, intolerance of, or for
whom cyclosporine A (CsA) treatment was medically inadvisable in the LIBERTY AD CAFÉ
RCT (de Bruin-Weller et al. 2018). Dupilumab’s efficacy was sustained up to 76 weeks in adults
(Deleuran et al. 2020) and 52 weeks in adolescents and children in various OLE studies (Cork et al.
2020; Cork et al. 2021).
Dupilumab leads to significant and rapid improvements in daily peak pruritus Numerical
Rating scale (NRS) by day 2 in adults and day 5 in adolescents (Silverberg et al. 2020a). Dupilumab
treatment showed rapid and sustained improvements in the magnitude of itch, starting with the first
dose; responses progressively increased and were sustained through to the end of treatment up to 1
year. In addition to improving signs and symptoms of AD, dupilumab led to clinically significant
improvement in comorbid asthma and/or sinonasal disease, if present (Boguniewicz et al. 2021).
Real-World Studies
Real-world studies, including a meta-analysis (Halling et al. 2021), supported dupilumab’s efficacy
in the treatment of AD, producing similar results to preceding clinical trials. In one particular
real-world study (Ariens et al. 2020), dupilumab was efficacious in the treatment of
difficult-to-treat AD, with over half of patients previously failing treatment on ≥ 2 immunosuppressive
drugs, as evidenced by improvement in EASI score and PROs, such as pain, itch, anxiety/depression
and QoL.
Table 2. Biologics for treatment in AD.
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Biologic Target FDA Approval
for AD
Dupilumab
Tralokinumab
Lebrikizumab
Nemolizumab
IL-4Rα (impacts
IL-4 and IL-13)
IL-13
IL-13 Not determined Not determined SC
IL-31 60 mg Q4W SC
ü
ü
Age Approved
for AD
> 6 years Adults:
> 18 years 300 mg (after 600 mg
Dosing and Frequency for AD Route Phase 3 Clinical Trial results
300 mg (after 600 mg
LD)
Pediatrics (Weight
based)
15 to < 30 kg:
300 mg (600 mg LD)
30 to < 60 kg:
200 mg (400 mg LD)
> 60 kg:
300 (600 mg LD)
LD)
Q2W
Q4W
Q2W
Q2W
Q2W
* Can increase to
Q4W if disease well
controlled after 16
weeks
SC
SC
AD Severity
(EASI; IGA)
ü ü ü
ü ü ü
ü
* DoseDependent
* Only phase 2 Data available for lebrikizumab
ü ü
Pruritus S. Aureus
Colonization
* Phase 2 results
(Not evaluated)
ü
(Not evaluated)
Targeted and Biologic Therapeutics for Allergic and Immunologic Diseases 229
Table 3. Janus Kinase (JAK) inhibitors being investigated in AD.
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230 Textbook of Diagnostic and Therapeutic Procedures in Allergy
JAK
inhibitor
Ruxolitinib
Delgocitinib
Tofacitinib
Abrocitinib
JAK
Selectivity
JAK 1
JAK 2
JAK1
JAK2,
JAK3
TYK 2
JAK 1
JAK3
JAK 1
FDA Indications Age
Approved
for AD
Mild-moderate
AD (2021)
Oral:
Myelobrosis
PV
GVHD
-*Approved in
Japan for AD
RA
UC
pcJIA
PsA
Moderate-severe
AD (2022)
> 12 years 1.5%
--- --- --- Topical
--- 2%
> 18 years 100–200 mgOnce
Dosing and
Frequency for
AD
Twice
cream
ointment
daily
(up to
20%
BSA)
Twice
daily
daily
Route of
Administration
Topical
Topical
Oral
Phase 2 and 3 RCT
results
AD Severity
(EASI/IGA)
ü ü
ü ü
ü
*Only phase
2 RCT
ü ü
Pruritus Common AEs
* As
early as
the rst
12 hours
* As
early as
the rst
night
* As
early as
day 2 of
treatment
* As
early as
day 2 of
treatment
Adverse Eects
Reported in RCTs
Nasopharyngitis
URTI
Headache
Application site
reactions
AD
Nasopharyngitis
Contact dermatitis
Acne
Application site
folliculitis
Nasopharyngitis
ü
Contact dermatitis
Headache
Nausea
Headache
Acne
Change in Lab
Parameters in
RCTs
Transient platelet
increase (~week 2)
--- ---
CPK elevation
increased LDL,
HDL
decreased platelets
Black Box
Warning
ü
Serious
infections,
mortality,
malignancy,
MACE and
thrombosis
ü
Serious
infections,
mortality,
malignancy,
MACE and
thrombosis
ü
Serious
infections,
mortality,
malignancy,
MACE and
thrombosis
Updacitinib
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Baricitinib
Key: PV: Polycythemia Vera; GVHD: Graft versus Host Disease; BSA: body surface area; RA: Rheumatoid Arthritis; UC: Ulcerative Colitis; pcJIA: polyarticular course juvenile idiopathic
arthritis; PsA: psoriatic arthritis; CPK: creatine phosphokinase; LDL: Low-density lipoprotein; HDL: high-density lipoprotein
JAK 1
JAK 1
JAK 2
Moderate-severe
AD (2022)
RA
PsA
RA
*Approved in the
EU and Japan
for AD
> 12 years*
and Less
than 65
years
* Must
weigh at
least 40 kg
--- 1, 2 or 4
15–30 mgOnce
mg
*Doses
used in
phase 3
RCTs
daily
Once
daily
Oral
Oral
ü ü
* As
early
as day
2-3 of
treatment
ü ü
Acne
URTI
Nasopharyngitis
AD
Headache
Nasopharyngitis,
Headache
Diarrhea
CPK elevation
increased LDL,
HDL
Transaminitis
Cytopenia (anemia;
neutropenia)
CPK elevation
Increased LDL,
HDL
Creatinine elevation
Hematologic
changes (anemia,
lymphopenia,
neutropenia and
thrombocytosis)
ü
Serious
infections,
mortality,
malignancy,
MACE and
thrombosis
ü
Serious
infections,
malignancy
and
thrombosis
Targeted and Biologic Therapeutics for Allergic and Immunologic Diseases 231
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