Use of anti–IL-5 therapy in a patient with T2 inflammation–driven CRSwNP, HES, and asthma in a multidisciplinary clinic

History and presentation
A 70-year-old female has a history of adult-onset asthma managed with a moderate-dose budesonide/formoter­ol inhaler. In 2019, she presented with skin rash and neuropathy (numbness). Complete blood counts showed ele­vated absolute eosinophil, peaking at 6,000 cells/μL. In conjunction with skin biopsy and nerve conduction studies, the diagnosis of hypereosinophilic syn­drome (HES) was made.

The patient was prescribed oral prednisolone 50 mg and mycophe­nolate mofetil (MMF), with good initial response. Her eosinophil counts re­mained high upon tapering of steroids, and she was recommended to switch to an anti–interleukin-5 (IL-5) mono­clonal antibody (mAb), mepolizumab, to prevent side effects of long-term steroid use. However, she refused bi­ologic treatment due to financial con­straints. After 8 months, prednisolone was tapered off and she was main­tained on low-dose MMF.

After 2 years, the patient had an asthma exacerbation and progres­sive nasal symptoms, including loss of smell and nasal obstruction. She was referred to our joint Allergy and Ear, Nose & Throat (ENT) clinic and nasal endoscopy confirmed chron­ic rhinosinusitis with nasal polyps (CRSwNP). She was restarted on oral prednisolone.

Treatment and response
The patient initially declined surgery despite persistent symptoms whilst on first-line treatment, including intranasal steroids, nasal irrigation, and short-term oral steroids. She had persistent nasal and asthmatic symptoms, with a high blood eosinophil count (BEC) of 3,000 cells/μL, and she was unable to taper off maintenance oral steroids (3–5 mg/day) for the following 2 years.

However, her nasal symptoms worsened, with complete anosmia (Top International Biotech Smell Iden­tification Test [TIBSIT] score, 0), sleep disturbances and snoring due to nasal obstruction.

Consequently, the patient under­went bilateral functional endoscopic si­nus surgery (FESS). To reduce the size of nasal polyps and minimize potential complications, mepolizumab 100 mg subcutaneous (SC) injection Q4W was initiated 2 weeks prior to surgery. After her first mepolizumab dose, there was rapid reduction in BEC, from 7,000 cells/μL prior to surgery to nearly zero. (Figure 1) Mepolizumab was continued postoperatively.

Six months after FESS and mepo­lizumab treatment, her sense of smell gradually improved. Six months post­operative endoscopic examination revealed complete resolution of nasal polyps bilaterally with no relapse. Her Asthma Control Test (ACT; range, 0–25) score improved from 21 to 25, 22-item Sino-Nasal Outcome Test (SNOT-22; range, 0–110) score improved from 31 to 0, Total Nasal Symptom Score (TNSS; range, 0–12) reduced from 10 to 0, and TIBSIT score (range, 0–43) increased from 0 to 6. (Figure 2) Pred­nisolone and MMF were discontinued shortly afterwards, with good disease control while maintaining a normal BEC level. (Figure 1) There was no re­lapse of rash or neuropathy, and her asthma was well controlled with no ex­acerbations, requiring only a low dose of budesonide/formoterol.

Overall, the patient tolerated me­polizumab 100 mg well with no ad­verse events and maintained good disease control of CRSwNP, asthma and HES.

Discussion
CRSwNP is characterized by chronic local eosinophilic inflamma­tion, primarily type 2 (T2) inflammation, with IL-5 playing a central role in driv­ing the pathogenic pathway. Standard first-line treatments for CRSwNP typi­cally include intranasal corticosteroids, saline irrigation, and short courses of systemic corticosteroids.¹ Nasal sur­gery is considered for those not re­sponsive to first-line treatments, but postoperative recurrence rate remains high, with 35 percent of patients ex­periencing recurrence within 6 months after FESS.² Biologics, including the anti–IL-5 mAb, mepolizumab, have emerged as effective newer treatment options.¹

Latest European Position Paper on Rhinosinusitis and Nasal Polyps/ European Forum for Research and Ed­ucation in Allergy and Airway Diseases (EPOS/EUFOREA) guidelines recom­mend the use of biologics in CRSwNP in patients with bilateral polyps who have previously undergone FESS and show evidence of T2 inflammation.³ It is important to differentiate those with T2 inflammation who should initiate bi­ologics to reduce the risk of postoper­ative recurrence.⁴ Presence of param­eters suggestive of T2 inflammation include concomitant comorbidities (eg, HES, asthma and chronic sponta­neous urticaria), bilateral polyps, early postoperative recurrence, and elevat­ed eosinophil counts, all of which can guide treatment decisions.

As demonstrated in our case, treatment with mepolizumab helps reduce long-term steroid use, which is especially important for elderly pa­tients who are at increased risk of side effects such as osteoporosis.⁵

In the randomized, double-blind, placebo-controlled phase III SYNAPSE trial involving 407 adults with recurrent, refractory severe bilateral CRSwNP, mepolizumab significantly reduced the use of systemic corticosteroids com­pared with placebo (odds ratio [OR], 0.58; 95 percent confidence interval [CI], 0.36–0.92; p=0.02).¹

The bothersome symptoms of CRSwNP can greatly impact patients’ quality of life. Anosmia diminishes the enjoyment of meals and poses safety risks, such as inability to detect burn­ing odours, while nasal obstruction disrupts sleep, resulting in obstruc­tive sleep apnoea, which leads to daytime sleepiness and affects daily activities.^6,7

Treatment with mepolizumab al­lowed our patient to gradually regain the sense of smell and have better sleep quality, enhancing her overall well-being. The SYNAPSE trial demon­strated sustained improvements in health-related quality of life with me­polizumab, showing a significant re­duction in SNOT-22 scores at week 52 vs placebo (mean change from base­line, -29.4 vs -15.7; 95 percent CI, -23.57 to -9.42; p=0.0032). Loss of smell visual analogue scale score sig­nificantly improved with mepolizumab vs placebo at weeks 49–52 (difference in mean, -1.51; 95 percent, -2.15 to -0.87; p<0.001). In the mepolizumab arm, patients with the largest improve­ments in their sense of smell had fewer prior sinus surgeries and shorter du­ration of nasal polyps, suggesting that early intervention with mepolizumab may lead to greater clinical benefit.¹

Beyond CRSwNP, mepolizum­ab effectively managed our patient’s HES and other T2-driven conditions, reducing the need for polypharma­cy. The efficacy of SC mepolizumab 300 mg has been demonstrated in mul­tiple clinical trials, including a 32-week randomized phase III trial (n=108), in which mepolizumab significantly re­duced the occurrence of ≥1 flare or study withdrawals in patients with HES (28 vs 56 percent; p =0.002).⁸ For severe asthma, SC mepolizumab 100 mg significantly reduced the rate of exacerbations by 53 percent (95 percent CI, 36–65; p<0.001) vs place­bo in the MENSA trial (n=576).⁹

In terms of safety, with up to 9 months of experience treating 10 adult patients with mepolizumab in our joint ENT–immunology clinic, only low rates of adverse events (AEs) were report­ed, with no significant safety con­cerns. Mepolizumab’s safety profile in SYNPASE was consistent with trials in other diseases, showing compara­ble rates of AEs and serious AEs vs placebo, with no new safety signals observed.¹

Although perioperative use of me­polizumab remains off-label, there is indication for use in asthma and HES (albeit requiring a higher dose).¹⁰ Af­ter thorough discussion with the pa­tient, with a hope to reduce polyp burden and surgical complications, lower blood eosinophil levels and re­duce recurrence after surgery, as well as reduce long-term steroid use, she agreed to proceed. More data are re­quired to assess the effectiveness, but patients with severe CRSwNP with high risk of recurrence may benefit from this treatment approach.

A clinic jointly operated by aller­gists/immunologists, ENT surgeons, and specialty nurses fosters multidis­ciplinary collaboration and is vital for managing patients with CRSwNP and associated conditions. Many patients referred to our clinic have experienced recurrences after initial surgery, neces­sitating comprehensive evaluations. This collaborative model encourages discussions about optimal surgical and systemic treatment strategies. In­sights from ENT specialists can also help identify causes of nasal polyp re­currence, allowing more tailored treat­ment decisions. For example, if recur­rence is due to surgical factors, such as incomplete clearance of polyps during the initial procedure, repeated surgery may be considered instead of initiating biologic therapy. Additionally, the joint clinic setting facilitates easi­er access to smell tests and biologic treatments.

Recognizing the interplay between T2 diseases was crucial in the effective management of this patient. Timely in­terventions with biologics such as me­polizumab can concomitantly manage CRSwNP, asthma and HES, minimize disease recurrence, reduce long-term steroid use and obviate repeated surgeries.