Tag Archives: flovent

NASPGHAN Alert: Flovent HFA Discontinuation

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12/7/23 NASPGHAN Alert: Guidance for Flovent HFA Upcoming Discontinuation Used For The Treatment of Eosinophilic Esophagitis

Situation:
Brand name Flovent HFA will no longer be manufactured after December 31, 2023.

Background:
• Flovent HFA is a commonly utilized swallowed topical steroid treatment for patients with eosinophilic esophagitis (EoE). It works by the patient swallowing the aerosolized medication dispensed by a metered dose inhaler (MDI).
• Both Medicaid and many private insurance formularies have transitioned to breath-actuated inhalers as their preferred inhaled steroid formulation, which cannot be used for EoE because they cannot be swallowed.
• GlaxoSmithKline will be discontinuing manufacture of brand Flovent HFA after December 31, 2023. While an authorized generic fluticasone HFA is available, it is not listed on many insurance formularies and for those that do include it, it is typically not listed as a preferred medication.
• Two other steroid MDIs are available on the market – Alvesco HFA (ciclesonide) and Asmanex HFA (mometasone). Limited data is available regarding dosing and efficacy in EoE 1,2.
• We are actively working to raise these concerns with major payors.

Assessment & Recommendation:
Given upcoming Flovent HFA discontinuation, patients needing this formulation of drug could be switched to generic fluticasone HFA. For many insurances this may require a prior authorization, which may delay initiation of the medication and families should be counselled accordingly.

In those whom generic fluticasone HFA is denied despite submission of a prior authorization, alternative options include:
• Oral viscous budesonide
• Swallowed topical Asmanex (mometasone) HFA or Alvesco (ciclesonide) HFA. Data on dosing in EoE is limited and these medications are also likely to require a PA.

References:
1. Tytor J, Larsson H, Bove M, Johansson L, Bergquist H. Topically applied mometasone furoate improves dysphagia in adult eosinophilic esophagitis – results from a double-blind, randomized, placebo-controlled trial. Scand J Gastroenterol. 2021 Jun;56(6):629-634. doi: 10.1080/00365521.2021.1906314. Epub 2021 Apr 8. PMID: 33831327.
2. Nistel M, Nguyen N, Atkins D, Miyazawa H, Burger C, Furuta GT, Menard-Katcher C. Ciclesonide Impacts Clinicopathological Features of Eosinophilic Esophagitis. J Allergy Clin Immunol Pract. 2021 Nov;9(11):4069-4074. doi: 10.1016/j.jaip.2021.06.058. Epub 2021 Jul 19. PMID: 34293498.

The information provided is intended solely for educational purposes and not as medical advice. It is not a substitute for care by a trained medical provider. NASPGHAN does not endorse any of these products and is not responsible for any omissions. For additional information please email floventquestions@naspghan.org.

Any substitution should only be done under the recommendation and supervision of a healthcare professional. 

Higher Doses of Topical Steroids for Eosinophilic Esophagitis

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A recent randomized, double-blind, placebo controlled study (Gastroenterol 2014; 147: 324-33) examined “high-dose” fluticasone propionate (FP) for patients, aged 3-30 years, with eosinophilic esophagitis (EoE).  FP patients received 1760 mcg divided into two doses for three months, then the dose was reduced in half.

Efficacy: Among the 28 FP patients, a complete remission (CR) (≤1 eosinophil/hpf on histology) was evident in 65% compared with 0% CR in 14 placebo patients.  Furthermore, partial response (PR) (multiple definitions of responsiveness -see Figure 2) evident in about 75%.  Reduction in dose to 880 mcg/day resulted in 93% of EoE participants maintaining CR or PR.

Molecular response: The authors also studied the transcriptome prospectively in these patients with the “Eosinophilic esophagitis diagnostic panel” (EDP). “A large portion of the participants receiving FP in phase 1 showed a normalized signature compared with the dysregulated screening and placebo signatures….notably, the 6 FP participants with histologic PR or no remission also had a partial reversal with a signature different from the placebo group…However, there were still a few molecular nonresponders whose signatures failed to normalized upon FP treatment.”

Based on their study findings: the authors recommend assessment at 3 months after initiation of topical steroids because “extending the timeframe for high-dose FP to 6 months does not increase remission status.”

The authors could not identify any demographics or signs/symptoms that predicted response to high-dose FP. In addition, in this small cohort, no difference in adverse effects compared to placebo were found.

My take on this study is that it raises more questions than it answers.

  • Is the higher induction dose of FP really needed or would 880 mcg/day over a 6 month period result in the same findings?
  • Is FP superior to budesonide which is considered to have less systemic absorption?
  • Should we be using higher doses of budesonide as well?
  • Would patients be better off receiving systemic steroids and transitioning to topical steroids?
  • What are the long-term consequences, good and bad, in using higher steroid doses?

Take-home message: In a carefully designed study with molecular correlation, higher doses of Fluticasone achieved high rates of complete remission in EoE patients.  Except for elemental diets, no dietary therapies have shown to have a higher response rate.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

 

The undiscovered country

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The title of this blog is derived from a Star Trek movie.  I think that when we see patients with eosinophilic esophagitis that we are often seeing something new and poorly characterized.

Despite so many unanswered questions, particularly on an individual basis, this topic has seen a lot of interest and there are many advances in both bedside and basic research.  The review article  (Allergy 2012; DOI: 10: 10.1111/j.1398-9995.2012.02787.x) focuses on many of the similarities and differences between pediatric and adult patients.  Is it the same disease? (Probably yes)

With regard to medical history, the article reminds clinicians to ask about coping strategies:

  • do you wash food down with liquid?
  • are you the last one to finish your food?
  • do you chew your food a long time?
  • do you avoid foods like meats or breads?

Clinical features –main difference is greater presentation variety in children.  Adults almost always have long-standing dysphagia.  In pediatrics, painful symptoms, reflux symptoms, and feeding refusal are often seen in early stages.  In both populations, other atopic diseases are very common.

Immunopathogenesis (same in pediatrics and adults):  Th2-type inflammatory response; not just eosinophils but also IL-5-expressing T-cells, B cells, and IgE-bearing mast cells.  A break-down of all the types of quantified cells from a large number of studies is detailed (Table 2).

Allergic profile –main difference is much higher aeroallergen sensitization in adolescent & adult patients than in pediatric patients.  In children, top four allergens: milk, wheat, egg, and soy.  In older patients/adults, nuts are frequent food allergens.

Treatment strategies –basic question of whether to treat for symptomatic relief or histologic response is still debated.  Three goals of treatment are the same:

  • improve quality of life
  • reduce the risk of severe esophageal injury
  • prevent esophageal damage

3 D’s of treatment drugs, diet, dilatation:

Drugs: topical steroids (fluticasone, budesonide) are effective in ~50% of children & these agents may reverse subepithelial fibrosis, PPIs -small percentage have EoE PPI-responsive disease, & systemic steroids.  Lower doses of budesonide may be effective as maintenance treatment (0.25mg BID).  Interestingly, infliximab has not been effective clinically or histologically despite the high amounts of TNF.  Azathioprine (or 6-MP) was effective in three steroid-dependent patients in a pilot study.

Diet –review does not cover new territory (see previous blog: Eosinophilic Esophagitis -Six Food Group Diet).  States that elemental diets are not practical in adults.  Discusses the fact that food allergy identification is difficult & remains a pressing research need.

Dilatation –can provide long-lasting symptom relief.  Dilatation is infrequently utilized in pediatrics and virtually never in absence of other therapies.

On a side note, in my training I was taught that there were 3D’s to treating every patient: diet, drugs, and demeanor — a good attitude goes a long way, particularly in an uncertain world.

Additional references:

  • -Gastroenterology 2011; 141: 1593.  anti-IL-5.  partially effective for EoE.
  • -JPGN 2010; 51: 723. n=91.  Incidental gastric eosinophils does not predict a worse response to fluticasone then isolated EoE.
  • -Clin Gastro & Hepatology 2011; 9: 400 (editorial 370). Budesonide at dose of 0.25mg BID was partially effective in adult cohort of n=28.
  • -Aceves SS et al. Allergy 2010; 65: 109-116. 3 month course of budesonide can lead to resolution of esophageal remodeling. Lamina propria fibrosis resolution correlates with response to topical steroids. Examined effect on lamina propria after 3 months of Rx.
  • -Gastroenterology 2010; 139: 1526. n=36. (summary pg 1429) 15 day course of budesonide (1mg BID). 13/18 in Rx group had improved dysphagia, 72% wiht histologic remission, 92% reduction in eosinophil count. Did not seem to matter if “allergic” or not. 3 pts developed mild candida.
  • -Gastroenterology 2010; 139: 418. Randomized placebo study showed effectiveness.n=15 Rx (n=9 placebo). 87% of Rx group responded.  2ml of water with 0.5gm pulmicort and mixed it with 4-5 packets of splenda.
  • -JPGN 2007; 45: 281/370/319. Review/research symposium/subepithelial fibrosis associated with EoE & dysphagia.
  • -JPGN 2007; 45: 22-31. Th2 Immunity w Eotaxin-3/ C-C chemokine receptor in EoE.
  • -Gastroenterology 2006; 131: 1381-1391. Randomized double-blind, placebo-controlled trial of fluticasone for EoE: 880mcg divided bid; n=21 Rx, n=15 placebo. 50% (vs 9% controls) achieved histologic remission; Rx more effective in those w/o detectable food allergies. 67% (vs. 27% controls) resolution of vomiting.
  • -Clin Gastro & Hep 2007; 5: xxiv. EoE causing Boerhaave’s syndrome (spontaneous rupture)
  • INCREASED FRAGILITY: -Gastrointest Endosc 2003; 57: 407-12. -Clin Gastro Hepatolo 2003; 1: 433-37.
  • -Clin Gastro & Hep 2006; 4: 1328. absolute eosinophilia (AEC 440 vs 140 controls), eosinophil-derived neurotoxin, and eotaxin-3 act as biomarkers of EE activity.
  • -Gastroenterology2006; 131: 2018 (-J Clin Invest 2006; 116: 536-547. ) Eostaxin-3/EcE transcript signature.
  • -J Pediatr 2005; 147: 540 Picture of ringed esophagitis.
  • -JPGN 2004; 39: S8 [abstract 0005]. CHOP experience in 250 pts. NG elemental diet was most effective. ~6% of pts presenting with GER. Strict avoidance of allergens needed.