Medical Policy: 08.01.23 

Original Effective Date: February 2015 

Reviewed: January 2019 

Revised: January 2019 

 

Notice:

This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.

 

Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

 

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.

 

Description:

Fecal Bacteriotherapy, also called fecal microbiota transplantation (FMT) involves the infusion of intestinal microorganisms via transfer of stool from a healthy individual into a diseased individual, with the intent of restoring normal intestinal flora. Fecal transplant is proposed for the treatment of treatment-refractory Clostridioides (previously Clostridium) difficile infection (CDI).

 

The US Food and Drug Administration (FDA) has classified human stool as a biological agent and determined that its use in fecal microbiota transplantation (FMT) therapy and other research should be regulated to ensure patient safety.

 

Fecal transplantation is usually performed by colonoscopy and less commonly by nasoduodenal tube. During colonoscopy the colonoscope is advanced through the entire colon. As the colonoscope is withdrawn, the donor stool is delivered through the colonoscopy into the colon.

 

Current guidelines state that the preferred route of administration of FMT is colonoscopy due to risk for aspiration and long-term bacterial overgrowth in the small intestine following NG or enteroscopy administration.

 

The goal of FMT is to replace damaged and/or disordered native microbiota with a stable community of donor microorganisms. The treatment is based on the premise that an imbalance in the community of microorganisms residing in the gastrointestinal tract (i.e., dysbiosis) is associated with specific disease states, including susceptibility to infection.

 

Oral tablets

OpenBiome has collaborated with Finch Therapeutics to develop CP101, a freeze-dried oral FMT capsule.

 

Food and Drug Administration (FDA)

In July 2013, the U.S. Food and Drug Administration (FDA) issued guidance regarding investigational new drug requirements for use of fecal microbiota transplant to treat CDI not responsive to medication therapy. The document states that FDA is continuing to consider how to regulate fecal microbiota transplant and that, during this interim period, the agency will use enforcement discretion regarding use of fecal transplant to treat treatment-resistant CDI infections. FDA requires that physicians obtain adequate informed consent from patients or their legal representative before performing the intervention. The FDA is allowing clinicians to treat these patients without completing an Investigational New Drug application (IND). Clinicians must file an IND in order to perform FMT for any other purpose.

 

Guidelines and Position Statements

The American College of Gastroenterology

The American College of Gastroenterologyrecommends that FMT should be considered second-line therapy for a third recurrence of CDI.

 

Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)

In 2018, IDSA and SHEA updated the 2010 clinical practice guidelines for the diagnosis and treatment of clostridium difficile infection in adults and children. The Societies recommended pharmacotherapy using vancomycin, fidaxomicin, and/or metronidazole depending on the episode and the severity of the C difficile.

 

The guidelines strongly recommended fecal microbiota transplantation (FMT) as a treatment option for adults following an initial treatment of CDI and two recurrences (i.e. after three treated CDI episodes) that have been non-responsive to at least two regimens of antibiotics (i.e., various combinations of vancomycin, fidaxomicin, and/or metronidazole). Similar recommendations are made for children but the strength of the recommendations is low and the quality of evidence is low for pharmacotherapy and very low for FMT.

 

The Societies recommendations for the treatment of C. difficile included the following:

  • Initial episodes, non-severe: oral vancomycin (VAN) 125 mg four times a day for ten days; OR oral fidaxomicin (FDX) 200 mg twice a day for ten days; OR if neither VAN or FDX are available, oral metronidazole 500 mg three times a day for ten days.
  • Initial episode, severe: oral VAN 125 mg, four time a day for ten days; OR FDX 200 mg twice a day for ten days
  • Initial episode, fulminant; 500 mg VAN oral or via NG tube four times a day. If ileus is present consider rectal instillation of VAN. Intravenous metronidazole, 500 mg every eight hours, with VAN if ileus is present.
  • First recurrence: VAN 125 mg four times a day for ten days if metronidazole was used for initial episode; OR prolonged tapered and pulsed VAN regimen if a standard VAN regimen was used initially; OR FDX 200 mg twice a day for ten days if VAN was used for the initial episode.
  • Second or subsequent recurrence: VAN in tapered and pulsed regimen; OR oral VAN 125 mg four times a day for ten days followed by rifaximin 400 mg three times a day for 20 days; OR FDX 200mg twice a day for 10 days; OR fecal microbiota transplantation (IDSA, 2018).

 

While the previous guidelines recommended metronidazole as the first-line therapy for initial cases of mild-to-moderate CDI and vancomycin for more severe cases, the new guidelines recommend either vancomycin or fidaxomicin (FDX) as the drug of choice for all initial episodes.

 

Prior Approval:

Not applicable.

 

Policy:

Fecal microbiota transplantation/fecal bacteriotherapy may be considered medically necessary in patients >/= 18 years of age when ALL of the following have been met:

  • Infection confirmed by a positive stool test for Clostridioides (previously Clostridium) difficile infection
  • There have been at least 3 episodes of recurrent Clostridioides difficile infection and associated diarrhea refractory to antibiotic therapy including at least one of the following regimens:
    • tapered and pulsed vancomycin (VAN) or
    • vancomycin (VAN) 125mg four times a day for 10 days  followed by rifaximin 400 mg three times a day for 20 days or
    • fidaxomicin (FDX) 200mg twice a day for 10 days
  • Patient is not immunocompromised, including:
    • Patients on major immunosuppressive agents including high-dose corticosteroids, calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors, lymphocyte-depleting biological agents, anti-tumor necrosis factor agents, and others; chemotherapeutic antineoplastic agents.
    • Patients with decompensated liver cirrhosis, advanced HIV/acquired immune deficiency syndrome, recent bone marrow transplant, or other cause of severe immunodeficiency

 

The current studies fail to address and show success with repeated fecal transplants. Therefore, the use of repeat fecal transplant for any indication is considered not medically necessary.

 

Fecal bacteriotherapy is considered not medically necessary for the first or second episode of clostridium difficile.

 

Fecal microbiota transplantation/fecal bacteriotherapy is considered investigational for, but not limited to, the following conditions:

  • Alopecia Areata
  • Autism
  • Constipation
  • Crohn’s disease
  • Colon Cancer
  • D-lactic acidosis
  • Diabetes
  • Diarrhea not associated with Clostridioides difficil
  • Graft versus Host Disease
  • Irritable Bowel Syndrome
  • Inflammatory Bowel Disease
  • Obesity
  • Pouchitis
  • Ulcerative Colitis
  • Constipation
  • Multiple Sclerosis
  • Insulin resistance
  • Metabolic Syndrome
  • Neurologic disorders
  • Mental Health Disorders (e.g. anxiety, OCD, autism)
  • Other Autoimmune Disorders

 

Definitions

Recurrent Clostridioides (formerly Clostridium) difficile infection (CDI) is defined by complete abatement of CDI symptoms while on appropriate therapy, followed by reappearance of symptoms within two to eight weeks after treatment has been stopped.

 

Procedure Codes and Billing Guidelines:

To report provider services, use appropriate CPT* codes, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes.

  • 44705 Preparation of fecal microbiota for instillation, including assessment of donor specimen.
  • G0455 Preparation with instillation of fecal microbiota by any method, including assessment of donor specimen.
  • 44799 Unlisted procedure, small intestine

 

Selected References:

  • American College of Gastroenterology (ACG). Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections
  • Food and Drug Administration (FDA). Enforcement Policy Regarding Investigational New Drug Requirements for Use of Fecal Microbiota for Transplantation to Treat Clostridium difficile  infection Not Responsive to Standard Therapies. July 2013
  • Van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ (2013). Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. N Engl J Med 20 Jan 16.
  • NICE guideline: Faecal microbiota transplant for recurrent clostridium difficile infection March 2014
  • ECRI Institute, emerging technology reports. Fecal microbiota transplantation for treating recurrent clostridium difficile infection. Updated Aug 2014
  • Austin M, Mellow M, Tierney WM. Fecal microbiota transplantation in the treatment of clostridium difficile infections. Am J Med. 2014 Jun;127(6):479-83. doi: 10.1016/j.amjmed.2014.02.017. Epub 2014 Feb 26
  • Kelly CR, de Leon L, Jasutkar N. Fecal microbiota transplantation for relapsing Clostridium difficile infection in 26 patients: methodology and results. J Clin Gastroenterol. 2012;46:145–149
  • Kelly CP. Fecal microbiota transplantation--an old therapy comes of age. N Engl J Med. 2013;368:474–475
  • Vyas D, L’esperance HE, Vyas A. Stool therapy may become a preferred treatment of recurrent Clostridium difficile? World J Gastroenterol. 2013;19:4635–4637
  • Brandt LJ, Aroniadis OC. An overview of fecal microbiota transplantation: techniques, indications, and outcomes. Gastrointest Endosc. 2013;78:240–249
  • Moore T, Rodriquez A, Bakken JS. Fecal microbiota transplantation: a practical update for the infectious disease specialist. Clin Infect. Dis. 2014:58(4):541-545
  • Surawicz CM1, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR, Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for diagnosis, treatment, and prevention of clostridium difficile infections. Am J Gastroenterolo. 2013 Apr;108(4):478-98;  doi: 10.1038/ajg.2013.4
  • Borody TJ, Leis S, Pang G, et al. Fecal microbiota transplantation in the treatment of recurrent clostridium difficile infection
  • Brandt LJ, Aroniadis OC, Mellow M, et al.: Long-Term Follow-Up of Colonoscopic Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection. Am J Gastroenterol 2012; 107: 1079–87
  • Mattila E, Uusitalo-Seppala R, Wuorela M, et al.: Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection. Gastroenterology 2012; 142: 490–6
  • Allen-Vercoe E, Reid G, Viner N, Gloor GB, Hota S, Kim P, Lee C, O’Doherty K, Vanner SJ, Weese JS, et al. A Canadian Working Group report on fecal microbial therapy: microbial ecosystems therapeutics. Can J Gastroenterol. 2012;26:457–462.
  • Kelly CR, et al. Update on fecal microbiota transplantation 2015: indications, methodologies, mechanisms and outlook. Gastroenterol 2015 May 15 [Epub ahead of print].
  • Kelly CR, et al. Fecal microbiota transplant for treatment of Clostridium difficile infection in immunocompromised patients. Am J Gastroenterol 2014 Jul;109(7):1065-71.
  • Aroniadis OC, Brandt LJ, Greenberg A et al. Long-term Follow-up Study of Fecal Microbiota Transplantation for Severe and/or Complicated Clostridium difficile Infection: A Multicenter Experience. J Clin Gastroenterol. 2015 Jun 23.
  • Borody TJ, Leis S, Pang G, Wettstein AR. Fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection. UptoDate Inc., Waltham, MA
  • Varier RU, et al. Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection. Infect Control Hosp Epidemiol 2015 Apr;36(4):438-44.
  • Rossen NG, et al. Findings from a randomized controlled trial of fecal transplantation for patients with ulcerative colitis. Gastroenterol 2015 Mar 30 [Epub ahead of print].
  • Drekonja D, et al. Fecal microbiota transplantation for Clostridium difficile infection: A systematic review. Ann Intern Med 2015 May 5;162(9):630-8.
  • Malani PN, Rao K. Expanded evidence for frozen fecal microbiota transplantation for clostridium difficile infection: A fresh take. JAMA. 2016;315(2):137-138.
  • Almeida R, Gerbaba T, Petrof EO, et al. Recurrent Clostridium difficile infection and the microbiome. J Gastroenterol. 2016;51(1):1-10.
  • Lee CH, Steiner T, Petrof EO, et al. Frozen vs fresh fecal microbiota transplantation and clinical resolution of diarrhea in patients with recurrent clostridium difficile infection: A randomized clinical trial. JAMA. 2016;315(2):142-149.
  • Kakihana K, Fujioka Y, Suda W, et al. Fecal microbiota transplantation for patients with steroid-resistant/dependent acute graft-versus-host disease of the gut. Blood. 2016 Jul 26 [Epub ahead of print]
  • Fecal Microbiota Transplantation, FDA Emerging Clinical Issues (2016).
  • Quraishi MN, Widlak M, Bhala N, et al. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment Pharmacol Ther. Sep 2017;46(5):479-493. PMID 28707337
  • McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66:e1
  • Infectious Disease Society of America (ISDA). Fecal microbiota transplantation. Investigational new drug protocol. 2016. Accessed Jul 16, 2018. 
  • Infectious Disease Society of America (ISDA). Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Feb. 2018. Accessed Jul 16,2018. 
  • Mizuno, S, Masaoka, T, Naganuma, M, Kishimoto, T, Kitazawa, M, Kurokawa, S, Nakashima, M, Takeshita, K, et al. Bifidobacterium-Rich Fecal Donor May Be a Positive Predictor for Successful Fecal Microbiota Transplantation in Patients with Irritable Bowel Syndrome. Digestion. 2017;96(1):29-38. PubMed: 28628918 [PMID].
  • Johnsen, PH, Hilpusch, F, Cavanagh, JP, Leikanger, IS, Kolstad, C, Valle, PC, and Goll, R. Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial. Lancet Gastroenterol Hepatol. 2018;3(1):17-24. PubMed: 29100842 [PMID]
  • ECRI Institute, Fecal Microbiota Transplantation for Treating Irritable Bowel Syndrome (Health Technology Assessment Information: Hotline Response) Aug. 2018. 
  • Kao, D., Roach, R., Silva, M., et al. Effect of oral capsule vs colonoscopy delivered fecal microbiota transplantation on recurrent clostridium difficile infection: A randomized clinical trial. JAMA.  2017;318(20):1985-1993. doi:10.1001/jama.2017.17077. 
  • Biehl LM, Cruz Aguilar R, Farowski F, et al. Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection. Infection. 2018 Aug 14
  • Kang Y, Cai Y. Altered gut microbiota in HIV infection: Future perspective of fecal microbiota transplantation therapy. AIDS Res Hum Retroviruses. 2018 Jul 9
  • Bulik-Sullivan EC, Roy S, Elliott RJ, et al. Intestinal microbial and metabolic alterations following successful fecal microbiota transplant for D-lactic acidosis. J Pediatr Gastroenterol Nutr. 2018 Jun 12
  • Philips CA, Phadke N, Ganesan K, et al. Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis. Indian J Gastroenterol. 2018 Jun 21
  • Ding C, Fan W, Gu L, et al. Outcomes and prognostic factors of fecal microbiota transplantation in patients with slow transit constipation: Results from a prospective study with long-term follow-up. Gastroenterol Rep (Oxf). 2018;6(2):101-107.
  • Maharshak N, Ringel Y, Katibian D, et al. Fecal and mucosa-associated intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Dig Dis Sci. 2018;63(7):1890-1899.
  • Nusbaum DJ, Sun F, Ren J, et al. Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients. FEMS Microbiol Ecol. 2018;94(9).

 

Policy History:

  • January 2019 - Annual Review, Policy Revised
  • January 2018 - Annual Review, Policy Revised
  • January 2017 - Annual Revew, Policy Revised
  • January 2016 - Annual review, Policy revised
  • February 2015 - New policy

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

 

*CPT® is a registered trademark of the American Medical Association.