Pharmacologic Treatment of Eosinophilic Esophagitis: Efficacious, Likely Efficacious, and Failed Drugs

Eosinophilic esophagitis (EoE) has been independently described by Stephen Attwood (USA) and Alex Straumann (Switzerland) in 1993 and 1994, respectively [1, 2]. EoE is a chronic, local, immune-mediated esophageal disease, characterized, clinically, by symptoms related to esophageal dysfunction and, histologically, by eosinophil-predominant inflammation [3]. Other systemic and local causes of esophageal eosinophilia should be excluded. Over the last two decades, EoE has transformed from a rare condition to a disease that is commonly encountered with current incidence estimates ranging from 5 to 10 cases per 100,000, and current prevalence estimates ranging from 0.5 to 1 case per 1,000 [4, 5]. Concomitant allergies to various food antigens and/or aeroallergens are found in the majority of EoE patients [3]. In affected children, food refusal, gastroesophageal reflux disease (GERD)-like symptoms, vomiting, and abdominal pain are the leading symptoms, while adolescents and adults mostly present with dysphagia for solids and/or food impaction [3, 6]. Adult EoE patients frequently adapt to living with dysphagia by practicing various behaviors, such as food avoidance, food modification, or they take a longer time for ingestion of certain foods compared to other people eating that same food [7]. Histologic diagnosis is based on the presence of ≥15 esophageal eosinophils/high-power field (hpf) and exclusion of other diagnoses potentially associated with esophageal eosinophilia [3]. In the vast majority of patients, untreated, eosinophil-predominant inflammation leads to formation of strictures that are associated with the occurrence of food bolus impactions, which carry the inherent risk of esophageal perforations [5, 8]. In fact, once anti-eosinophil treatments are stopped, histologic or clinical relapse rates exceed 90% over a 1-year period [9]. Treatment options range from pharmacologic and diet therapies to esophageal dilation [10‒12]. The optimal long-term therapeutic approach still needs to be defined. EoE activity is assessed using a combination of patient-reported outcomes (PROs; encompasses EoE-related symptoms and quality of life) as well as histologic and endoscopic activity [13]. In randomized placebo-controlled trials, EoE-related symptoms are measured using an electronic daily diary, such as the Dysphagia Symptom Questionnaire (DSQ) or the symptom-based Eosinophilic Esophagitis Activity Index (EEsAI) PROs (recall period of 7 days), while histologic activity is assessed using the Eosinophilic Esophagitis Histologic Scoring System (EoE-HSS) that describes the grade and stage of eight distinct histologic features [14]. Endoscopic activity should be assessed using the Endoscopic Reference Score (EREFS) [14]. This review focuses on pharmacologic treatment options for EoE and will discuss neither food elimination diets nor esophageal dilation. In clinical practice, the therapy choice is strongly dependent on, among others, the EoE phenotype (purely inflammatory features vs. fibrotic features or a combination of both), presence of atopic comorbidities requiring treatment, the patient-perceived impact of the disease, and patient preferences.

The following section will highlight the current evidence to support the use of the different pharmacologic options for EoE treatment. The different drug classes and their approval status are highlighted in Table 1.

This section highlights the use of swallowed topical corticosteroids as induction and maintenance treatment. Safety aspects are also discussed.

Swallowed topical corticosteroids are efficacious in inducing histologic and clinical remission in pediatric and adult EoE patients. A meta-analysis of 7 studies with 250 participants found that symptomatic improvement was more frequently achieved in patients taking swallowed topical corticosteroids when compared to the control group (placebo or PPIs) (OR: 3.03, 95% confidence interval [CI]: 1.57–5.87) [18]. Histological remission was more frequently achieved in patients taking swallowed topical corticosteroids when compared to control groups (placebo or PPIs; 330 participants, OR: 13.66, 95% CI: 2.65–70.34) [18]. It should be noted that the comparison of results among different studies is limited by the variability in used agents (budesonide, fluticasone, ciclesonide), delivery systems (suspension, viscous slurry, swallowed puffs from inhalers, effervescent tablets), dosing, treatment periods, and the definition of histologic remission (ranges from <1 up to <20 eosinophils/hpf) and clinical remission (use of several, sometimes unvalidated PRO instruments) [13]. A comparative analysis of different dosages used in the various studies has been carried out in the recently published British EoE guidelines [49]. Dellon et al. [19] showed that, during an 8-week treatment duration, viscous topical budesonide (1 mg twice daily) was more effective than nebulized (and then swallowed) budesonide to reduce peak eosinophil counts per hpf (11 vs. 89, p = 0.02). In addition, authors showed that the medication contact time with the mucosa, as measured by scintigraphy, was higher for the group being treated with oral viscous budesonide (OVB) when compared to the group treated with nebulized budesonide (p < 0.005) [19]. In a double-blind, double-dummy trial lasting 8 weeks, OVB administered at the dose of 1 mg twice daily was equivalent to fluticasone multidose inhaler (MDI) administered at the dose of 880 μg twice daily in inducing histologic (71% OVB vs. 64% MDI, p = 0.38) and clinical response (posttreatment DSQ scores were 5 and 4 in the OVB and MDI groups, p = 0.70) [20]. Similar trends were noted for posttreatment total EREFS (2 vs. 3; p = 0.06) [20]. Esophageal candidiasis developed in 12% of patients receiving OVB and 16% of patients receiving MDI; oral thrush was observed in 3% and 2%, respectively [20]. One trial with 4 children evaluated ciclesonide, a topical glucocorticoid with less systemic absorption than fluticasone, and showed that symptoms as well as eosinophil counts decreased after 2 months of treatment [21]. A randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT, 1 mg twice daily; n = 59) or placebo (n = 29) showed that at 6 weeks, 58% of patients given BOT were in combined clinical and histologic remission compared with 0 patients given placebo (p < 0.0001) [15]. At week 6, histologic remission was achieved by 93% of patients given BOT versus no patients under placebo (p < 0.0001). After 12 weeks, 85% of patients had achieved combined clinical and histological remission [15]. Six-week BOT administration and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent [15]. Based on these results, in November 2017, budesonide in a form of a melting tablet (Jorveza^®) was the first esophagus-specific formulation to be granted approval by the European Medicines Agency as induction treatment for adults with EoE, benefitting from an orphan drug designation [50]. Jorveza^® is currently also available in Great Britain, Canada, and Australia.

The Food and Drug Administration approved in February 2024 EOHILIA^® 2 mg twice daily, an oral budesonide suspension (BOS, 2 mg/10 mL single-dose stick packs), based on efficacy and safety data from two multicenter, randomized, double-blind, parallel-group, placebo-controlled 12-week studies in patients aged 11 to 55 years [16, 51]. In both studies, patients received at least one dose of either BOS 2 mg twice daily or placebo orally twice daily. Efficacy endpoints included histologic remission (peak eosinophil count of ≤6/hpf) and the absolute change from baseline in DSQ combined score after 12 weeks of treatment. Significantly more patients receiving BOS achieved histologic remission versus placebo in study 1 (53.1% vs. 1%). In study 2, 38% of BOS-treated patients achieved histologic remission versus 2.4% of those in the placebo group. Absolute change from baseline in DSQ combined score in the BOS versus placebo groups in study 1 was −10.2 (1.5) versus −6.5 (1.8) and in study 2, −14.5 (1.8) versus −5.9 (2.1). Of note, BOS (EOHILIA^®) is only approved as induction treatment for 12 weeks, not as maintenance treatment.

EoE is a chronic progressive disorder with a high recurrence rate in the absence of anti-eosinophil treatment [22]. As such, the vast majority of patients need a long-term maintenance treatment. There is a paucity of studies evaluating the long-term efficacy (LTE) of swallowed topical steroids in pediatric and adult EoE patients. In a 50-week randomized, double-blind, placebo-controlled trial, Straumann et al. [23] evaluated the efficacy of swallowed topical budesonide suspension given at the dose of 0.5 mg/day versus placebo. Histologic remission, defined as <5 eosinophils/hpf, was found in 36% of patients in the budesonide group, while no patient in the placebo group remained in remission [23]. One important learning point from this landmark study was that the daily dosage of budesonide was too low to maintain EoE in histologic remission in the majority of patients. An open-label, prospective, single-center study in children examined age-dependent dosages of swallowed topical fluticasone from a metered dose inhaler. Patients enrolled in the study showed an improvement with respect to histology, endoscopy, and symptoms over a mean follow-up time of 24 months [24]. A recently published double-blind trial by Straumann et al. [9] compared the efficacy and safety of 2 dosages of BOT versus placebo in maintaining remission defined as absence of clinical and histologic relapse and no premature withdrawal for any reason in adults with EoE. Two hundred and four adults with EoE in clinical and histologic remission were randomly assigned to groups given BOT 0.5 mg twice daily (n = 68), BOT 1.0 mg twice daily (n = 68), or placebo twice daily (n = 68) for up to 48 weeks. After 48 weeks, 73.5% of patients receiving BOT 0.5 mg twice daily and 75% receiving BOT 1.0 mg twice daily were in persistent remission compared with 4.4% of patients in the placebo group (p < 0.001 for both comparisons of BOT with placebo) [9]. Median time to relapse in the placebo group was 87 days. This landmark study paved the way for the approval of BOT (Jorveza^®) as a maintenance therapy.

With respect to safety aspects, the use of swallowed topical corticosteroids in the short term and long term seems to be characterized by a favorable safety profile with no serious side effects. In the BOT (Jorveza^®) maintenance trial over 48 weeks, the frequency of adverse events was similar in the BOT and placebo groups. Of note, morning serum levels of cortisol were in the normal range at baseline and did not significantly change during treatment. Four patients receiving BOT developed asymptomatic, low serum levels of cortisol. Clinically manifested candidiasis was suspected in 16.2% of patients in the BOT 0.5 mg group and in 11.8% of patients in the BOT 1.0 mg group; all infections resolved with treatment. There are conflicting results regarding the long-term use of swallowed topical steroids and their impact on adrenal suppression, particularly in children. Philla et al. [52] observed no differences in serum cortisol levels in 14 children treated with either swallowed fluticasone propionate (range 220–880 µg/day) or budesonide (range 0.5–1 mg/day) for a duration of 8–43 weeks. However, Golekoh et al. [53] documented adrenal suppression in 10% of children (n = 58) treated with swallowed topical steroids for ≥6 months. No symptoms of adrenal insufficiency or impaired growth were reported so far. Inhaled topical steroids for asthma treatment are associated with an increased risk for osteoporosis [54]. Such an association has not yet been described for swallowed topical corticosteroids in EoE.

In conclusion, swallowed topical steroids appear to be efficacious/effective in inducing clinical and histologic remission in pediatric and adult EoE patients. This class of medications appears to have a favorable safety profile. The oral budesonide tablet (BOT, Jorveza^®) has been approved for induction and maintenance treatment of adults with EoE in several countries outside the USA, while the oral budesonide suspension (BOS, EOHILIA^®) has been approved as induction treatment only for adolescents and adults with EoE in the USA. Given that no swallowed topical corticosteroid-based product has been approved yet for treatment of pediatric EoE patients under age of 11 years, several extemporaneous preparations of swallowed topical corticosteroids will continue to be used in this population. Long-term follow-up of EoE patients in prospective cohort studies will be best suited to systematically document long-term side effects associated with this class of medication [55].

GERD may mimic, coexist with, or exacerbate EoE [56]. On the other hand, EoE can also contribute to GERD activity by impacting esophageal clearance [57]. EoE patients may profit from PPI therapy, as it reduces acid production in patients with coexistent GERD and inhibits homing of eosinophils to the esophageal mucosa [58]. PPIs may also be used in patients with established EoE, as the altered esophagus may be more sensitive to physiologic acid exposure [59]. While in mechanistic terms PPIs may be useful as single or add-on therapy, it is important to remember that as of today no placebo-controlled trial has been conducted to evaluate PPI efficacy in EoE.

A recently published systematic review and meta-analysis, guided by the AGA Institute and the Joint Task Force on Allergy-Immunology Practice Parameters, evaluated the efficacy of PPIs for the endpoint “not achieving histologic remission” (defined as <15 eosinophils/hpf) for a treatment duration of 8 weeks in 23 studies with a total of 1,051 participants [25]. Authors found that 58.3% (unweighted) of subjects on PPIs failed to achieve histopathologic remission compared to 86.7% (unweighted) of a placebo control group [58]. As such, the relative effect of PPIs for not achieving histologic remission was 0.66 (95% CI: 0.61–0.72). When assessing the quality of evidence, the certainty in the effect estimate was considered to be very low and the certainty in the estimate was downgraded given very inconsistent results in absolute terms [25]. Of note, the authors did not evaluate the relative effect of PPIs on symptom improvement in EoE [25]. A systematic review and meta-analysis published in 2016 that included 33 studies with 619 patients showed that PPIs led to histological remission (defined as <15 eosinophils/hpf) in 50.5% (95% CI 42.2–58.7%) and symptomatic improvement in 60.8% (95% CI 48.4–72.2%) of patients [26]. The authors detected no significant differences in patients’ age, study design, and type of PPIs used [26]. They observed a trend for increased clinical and histologic efficacy when PPIs were given twice daily when compared to an administration once daily and also in patients with a pathological pH monitoring [26]. Furthermore, the authors provided a word of caution regarding the interpretation of their findings due to poor-quality evidence, heterogeneity in results, and publication bias in favor of studies reporting histological responses to PPIs. PPIs may also be effective in maintaining clinical and histologic remission. A prospective study in a pediatric cohort showed that most patients (78%) remained in clinico-pathologic remission at the 1-year follow-up on maintenance PPI therapy [27]. The first long-term follow-up multicenter study in 75 adult patients revealed that all patients who temporarily discontinued PPI therapy had a symptomatic and/or histologic relapse [28]. A total of 73% of patients maintained histological remission after at least 1 year when PPI dosages were tapered to the minimum effective clinical dose. Most patients who relapsed regained histological remission after dose escalation, which suggests that some patients might require high-dose PPI therapy in the long-term run [28]. PPIs are prescribed off-label for treatment of pediatric and adult EoE patients. It is very unlikely that PPIs will be granted official approval by regulatory authorities in the near future given the low interest of pharmaceutical companies to invest in clinical trials in EoE.

Systemic steroids are not recommended for use in EoE given their side-effect profile and the generally high efficacy of topical swallowed steroids [3, 49]. One randomized trial evaluated oral prednisone (n = 40) versus swallowed topical fluticasone (n = 40) in pediatric EoE patients [31]. At week four, almost all patients, irrespective of the treatment group, were free of symptoms, whereas histologic improvement was noted to be greater in the prednisone group. As expected, glucocorticoid side effects were more frequently observed in the prednisone group when compared to the fluticasone group [31].

One case series with 3 patients documented a clinical and histologic response on azathioprine or 6-mercaptopurine in EoE patients dependent on prednisone [32]. One factor limiting the use of these drugs is their side-effect profile [33].

Several anti-allergic drugs were evaluated for EoE treatment but failed to show a clinically relevant benefit regarding histologic activity or EoE-related symptoms. A 4-week trial of the mast cell stabilizer sodium cromoglycate failed to show either symptomatic or histologic improvement in 14 children with EoE [34]. Montelukast is a leukotriene D4 receptor antagonist. In open-label trials, montelukast use in high doses in adults and standard doses in children led to a symptomatic improvement but failed to demonstrate a histologic response [35, 36]. In a randomized controlled trial, Alexander and coworkers found that montelukast (20 mg per day) was not superior to placebo in maintaining remission induced by swallowed topical steroids [37]. Similarly, montelukast failed to maintain remission induced by swallowed topical steroids in a prospective study in adult EoE patients with reappearance of symptoms and histologic inflammation within a period of 3 months [38].

One randomized, double-blind, placebo-controlled study evaluated the efficacy of the oral prostaglandin D2 receptor antagonist OC000459 [60]. A total of 26 adult patients with steroid-dependent or steroid-refractory EoE were randomized to either receive OC000459 or placebo. At week 8, OC000459 but not placebo was associated with a significant reduction in esophageal eosinophil counts and an improvement in symptoms; however, no normalization of esophageal biopsies was documented [60].

Dupilumab (Dupixent^®), a monoclonal antibody targeted against IL-4 and IL-13, was approved by the US Food and Drug Administration in May 2022 for treatment of adolescent (≥12 years) and adult patients with EoE. Dupilumab is also approved by regulatory authorities in Europe and Canada. In Europe, including Switzerland, Dupixent^® is approved for treatment of EoE patients of at least 12 years of age with at least 40 kg body weight if these patients are either unresponsive or intolerant to or not candidates for conventional EoE therapies. The approval was based on the positive results of a three-part, phase 3 trial, in which patients 12 years of age or older underwent randomization in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo (part A) or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every 2 weeks or weekly placebo (part B) up to week 24 [17]. Eligible patients who completed part A or part B continued the trial in part C. The two primary endpoints at week 24 were histologic remission (≤6 eosinophils per hpf) and the change from baseline in the DSQ score. In part A, histologic remission occurred in 25 of 42 patients (60%) who received weekly dupilumab and in 2 of 39 patients (5%) who received placebo (difference, 55 percentage points; 95% CI: 40–71; p < 0.001). In part B, histologic remission occurred in 47 of 80 patients (59%) with weekly dupilumab, in 49 of 81 patients (60%) with dupilumab every 2 weeks, and in 5 of 79 patients (6%) with placebo (difference between weekly dupilumab and placebo, 54 percentage points; 95% CI: 41–66 [p < 0.001]; difference between dupilumab every 2 weeks and placebo, 56 percentage points; 95% CI: 43–69 [not significant per hierarchical testing]). The mean (±SD) DSQ scores at baseline were 33.6 ± 12.41 in part A and 36.7 ± 11.22 in part B; the scores improved with weekly dupilumab as compared with placebo, with differences of −12.32 (95% CI: −19.11 to −5.54) in part A and −9.92 (95% CI: −14.81 to −5.02) in part B (both p < 0.001) but not with dupilumab every 2 weeks (difference in part B, −0.51; 95% CI: −5.42 to 4.41). There was a favorable side-effect profile in patients under dupilumab. Given that dupilumab is also approved by European and the US regulators for treatment of moderate-to-severe atopic dermatitis, moderate-to-severe asthma, and chronic rhinosinusitis with nasal polyposis, this medication may be particularly useful in EoE patients with these atopic comorbidities requiring treatment.

Cendakimab is a monoclonal antibody against IL-13. In a placebo-controlled double-blind phase II trial during 16 weeks in 99 patients, cendakimab 360 mg sc once weekly showed significant reductions of peak eosinophil counts, endoscopic severity, and EoE-related symptoms (measured by the dysphagia symptom diary, DSD) as compared to placebo-treated patients [29]. Cendakimab showed a favorable safety profile. The most common adverse events were headache and upper respiratory tract infection. The LTE and safety of cendakimab were evaluated in the open-label extension study in 66 patients who completed the 16-week induction portion of the abovementioned phase 2 study [30]. Patients received 360 mg cendakimab sc once a week for 52 weeks. By week 12 of the LTE, esophageal eosinophil mean and peak counts, total EREFS, and EoE-HSS grade and stage scores did not differ considerably between patients who originally received placebo versus cendakimab. Most patients maintained responses through week 52. The rates of patients in symptomatic remission as measured by the EEsAI PRO instrument (score ≤20) increased from 14% at LTE entry to 67% at LTE week 52 in placebo-treated patients switched to cendakimab and from 30% at LTE entry to 54% at LTE week 52 in patients treated with cendakimab during both double-blind and open-label extension phases of the program [7]. Of the 28 patients who did not have a histologic response to cendakimab during the double-blind induction phase, 10 patients (36%) achieved response during the LTE. The most common adverse events were upper respiratory tract infection (21%) and nasopharyngitis (14%). A large phase III study evaluating cendakimab has completed recruitment, and first results are to be expected in 2024.

Mepolizumab and reslizumab are both anti-IL-5 monoclonal antibodies that have been evaluated nearly a decade ago in three randomized, double-blind, placebo-controlled trials in children, adolescents, and adults with EoE [39‒41]. All three trials showed a significant reduction of esophageal eosinophilic infiltrations; however, histologic remission was not observed. An improvement in EoE-related symptoms was found in two studies [40, 41].

Benralizumab is a monoclonal antibody against the IL-5 receptor. The drug is already on the market for severe eosinophilic asthma that is insufficiently controlled using standard therapy. Benralizumab is capable of killing eosinophils via a dual mechanism: the blockade of IL-5-mediated survival of these cells and the enhancement of eosinophil apoptosis induced by activation of the FcγRIIIa receptor of NK cells. The double-blind placebo-controlled MESSINA trial evaluated the efficacy and safety of benralizumab in adolescent and adult patients with active EoE and assessed at week 24 the proportion of patients with a histologic response, defined as a peak esophageal eosinophil count ≤6/hpf, and mean changes from baseline in DSQ [42]. According to a press release from AstraZeneca end of 2022, the endpoint of histologic remission at week 24 was achieved, but there was no difference in DSQ when compared to placebo. The study results are not yet published in a form of a peer-reviewed paper. The results of this study indicate that drugs that selectively deplete eosinophils are not sufficient to improve EoE-related symptoms, as other cells of the Th2 cascade likely play a role in promoting and maintaining inflammation of the esophagus [61]. Drugs, such as dupilumab or cendakimab, with a more upstream mechanism of action, are likely better suited to treat EoE.

Sialic acid-binding immunoglobulin-like lectin 8 (Siglec-8) is an inhibitory receptor expressed on eosinophils and mast cells. Lirentelimab is a humanized, anti-Siglec-8 monoclonal antibody that is capable of depleting tissue and blood eosinophils [44]. Lirentelimab has proven efficacy in Th2 diseases, such as conjunctivitis (NCT03379311) and urticaria (NCT03436797). Lirentelimab was the first biologic to be investigated for its efficacy in a randomized placebo-controlled trial in 65 adults with eosinophilic gastritis or eosinophilic duodenitis [45]. Assessment of eosinophil counts in the gastric and duodenal tissues was performed before and following 12-week treatment; assessment of esophageal eosinophilia was carried out in those patients, who had a prior diagnosis of EoE. Mean decrease in gastric/duodenal eosinophils was 86% in lirentelimab-treated patients compared to 9% in placebo [45]. Total symptom score decreased by 48% in the lirentelimab arm and only by 22% in the placebo arm. Sustained tissue eosinophil suppression was seen in patients participating in the open-label extension part of the study. Twenty patients with concomitant esophageal eosinophilia were analyzed in this study. Of the 14 patients treated with lirentelimab, 13 patients demonstrated resolution of esophageal eosinophilia. Of the 9 patients treated with placebo, only 1 patient reached that outcome. Although reduction in symptoms following treatment with lirentelimab was observed, complete symptom response was not reported. Lirentelimab was further evaluated in the phase III KRYPTOS study (clinicaltrials.gov NCT04322708) [46]. Group 1 (n = 93) was treated with a monthly injection of 1 mg/kg of lirentelimab for 6 months, group 2 (n = 91) received a monthly injection of 3 mg/kg of lirentelimab, and group 3 (n = 92) was treated with placebo. After 24 weeks, a histologic remission (≤6 eosinophils/hpf) was achieved in 92.5% (group 1), 87.9% (group 2), and 10.9% (placebo), respectively. However, change in DSQ was not different in lirentelimab-treated patients when compared to placebo. This trial shows that selective depletion of eosinophils and mast cells is not sufficient to provide symptomatic improvement. In addition, this study questions the utility of assessing eosinophil counts alone as an endpoint in randomized controlled clinical trials in EoE. Results of the KRYPTOS study have not been published yet as a peer-reviewed paper.

Omalizumab is a monoclonal anti-IgE antibody. A randomized, double-blind, placebo-controlled trial in adult EoE patients showed no benefits of omalizumab over placebo with respect to improvement in esophageal eosinophil counts and EoE-related symptoms [43].

Infliximab is a monoclonal antibody against tumor necrosis factor. Infliximab at a dosage of 5 mg/kg body weight was evaluated in 3 adult EoE patients. An induction treatment at weeks 0, 2, and 6 did not lead to an improvement of EoE-related symptoms and esophageal eosinophilia [47]. Other monoclonal antibodies against tumor necrosis factor, such as adalimumab or golimumab, have not been evaluated in EoE patients.

Vedolizumab is a monoclonal antibody against α4β7 that is expressed on T-lymphocytes and also eosinophils. Blockade of α4β7 inhibits the interaction with MAdCAM-1 expressed by endothelial cells of the gastrointestinal tract. The drug is marketed for treatment of patients with moderate-to-severe ulcerative colitis and Crohn’s disease. One case report of a patient suffering from Crohn’s disease and concomitant EoE described resolution of EoE, when the patient was switched from infliximab to vedolizumab [48].

A recently published systematic review and meta-analysis in 15 studies containing 1,813 patients evaluated the efficacy of the following drugs to induce histologic remission as well as clinical and endoscopic response: lirentelimab, budesonide orodispersible tablet (BOT, Jorveza^®), benralizumab, fluticasone orodispersible tablet, dupilumab (Dupixent^®), esomeprazole, budesonide oral suspension (BOS), fluticasone (aerosolized and then swallowed), cendakimab, mepolizumab, and budesonide (aerosolized and then swallowed) [62]. For histological remission defined as ≤15 eosinophils/HPF, BOT 1 mg two times per day ranked first. For failure to achieve symptom improvement, BOT 1 mg two times per day and budesonide oral suspension (BOS) 2 mg two times per day were significantly more efficacious than placebo. For failure to achieve endoscopic improvement based on the EoE EREFS, BOT 1 mg two times per day and BOS 1 mg two times per day or 2 mg two times per day were significantly more efficacious than placebo. The authors also mention that an important heterogeneity in eligibility criteria and outcome measures among available trials hampers the establishment of a solid therapeutic hierarchy.

Despite the fact that the first EoE patients have been described only 30 years ago, considerable progress has been made in evaluating different treatment options as well as in understanding the pathophysiology and the natural history of this condition. Therapeutic options in EoE include drugs, elimination diets, and esophageal dilation. Orodispersible budesonide tablets (Jorveza^®) have been approved by regulatory authorities for EoE treatment of adults in Europe, Canada, and Australia, but not in the USA. Jorveza^® is efficacious in inducing and maintaining histologic and clinical remission compared to placebo. An orodispersible budesonide suspension (BOS, Eohilia^®) was approved in February 2024 as induction treatment for adolescents of at least 11 years and adults with EoE in the USA only. Before the approval of Jorveza^® and Eohilia^®, several investigator-initiated clinical studies evaluated esophagus-targeted formulations of either budesonide or fluticasone to treat pediatric and adult EoE patients. These studies have generally shown that these medications are effective in inducing histological and clinical remission. Given the fact that PPIs are able to induce histologic and clinical remission albeit with very low quality of evidence and very inconsistent results of mostly observational studies, this class of medications is used off-label for EoE treatment of both pediatric and adult EoE patients. Dupilumab (Dupixent^®), a monoclonal antibody against IL-4 and IL-13, was approved by regulatory authorities in the USA, Europe, and Canada. Cendakimab (mAb against IL-13) is a promising candidate for EoE treatment; results of a phase III trial are expected in 2024. Due to lack of efficacy or unfavorable safety profile, the following drugs are not recommended for EoE treatment: systemic steroids, sodium cromoglycate, montelukast, azathioprine, infliximab, vedolizumab (mAb against α4β7), benralizumab (mAb against IL-5 receptor), mepolizumab (mAb against IL-5), reslizumab (mAb against IL-5), omalizumab (mAb against IgE), and lirentelimab (mAb against Siglec-8). LTE/effectiveness and safety data with the different drugs are currently sparse. Concerted efforts of different stakeholders will be necessary to continue the endeavor of providing our patients with much-needed therapies.

AS has received consulting fees and/or speaker fees and/or research funding from Adare/Ellodi, AstraZeneca, Dr Falk Pharma, Gossamer Bio, GSK, Celgene/Receptos/BMS, Regeneron-Sanofi. ES has received consulting fees and/or speaker fees and/or research funding from Dr Falk Pharma, GSK, Celgene/Receptos/BMS, Regeneron-Sanofi. She is an employee of Tillotts Pharma AG.

This work was supported by a grant from the Swiss National Science Foundation (32003B_204751/1 to A.M.S.) and the Swiss EoE foundation (to A.M.S).

Both authors contributed equally to drafting of the article, literature search, writing, and final approval.