Transcript Holtzmuller – Advice From A Peer

How To Get What
You Want
(Or What Your Patient Needs)
Kent C. Holtzmuller, MD, FACG
GI Service
Carolinas HealthCare System
Charlotte, NC
Common Targets of Denials
in GI
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IBD (diagnostics and therapeutics)
Hepatitis C therapy
Liver transplantation
PathFinderTG molecular testing (cyst fluid
analysis)
GERD endoscopic therapy
-59 modifier
Common Targets of Denials
in IBD
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Adalimumab and Infliximab levels and
antibodies (Anser ADA and Anser IFX)
Antibody panels to assist in diagnosis of IBD
IBD genetic testing
High-dose biologic therapy
Biologic therapies not approved for use in IBD
Why the Problems in IBD?
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High Cost Items
 Anser IFX/ADA ($2500.00)
Sensitivity and specificity issues with
diagnostic testing
Biologics (doses above standard rec. and some
resistance to step-down therapy)
Agents being used at doses outside of FDA
approval guidelines
No longer an Issue
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TPMT genotyping/phenotyping (once only)
6-TG and 6 MMPN levels. (for patients not
responding to Imuran/azathioprine)
Other Observations
Insurance carriers are not on the cutting edge of
approving new therapies and technology
FDA approval of a device signifies safety and not
necessarily efficacy.
Aetna Denial Policy 05/16
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Adalimumab and infliximab levels and antibodies
(Anser ADA and Anser IFX)
Antibody panels to assist in diagnosis of IBD
Testing for anti-chitobioside carbohydrate antibodies (ACCA), anti-laminaribioside carbohydrate
antibodies (ALCA), anti-mannobioside carbohydrate antibodies (AMCA), anti-chitin IgA (Anti-C), and
anti-laminarin IgA (Anti-L), anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces
cerevisiae antibodies (ASCA), anti-outer membrane porin C (OmpC) antibodies, anti-CBir1 flagellin
(anti-CBir1) antibodies,
NOD2/CARD15 genotyping
Fecal measurement of calprotectin
CD14 gene C-260T polymorphism testing, interleukin10-1082A/G polymorphism testing
Top-down biologic therapy unless fistulizing Crohn’s
What is the Problem with
IBD Serodiagnostic Panels?
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Low sensitivity (40-70%)
Still require the usual endoscopic, histologic and radiologic
evaluation for diagnosis
Value in differentiating isolated Crohn’s colitis from
ulcerative colitis is debated.
Technology assessment of serologic testing for IBD by the
Institute for Clinical Systems Improvement concluded that
the clinical utility of serologic testing in indeterminate
colitis has not been established.
Cost $690.00
Some concern that a neg. test may lead to delay in diagnosis
Case
32-yo male presents with RLQ pain and iron
deficiency anemia. + NSAID history.
 EGD and colonoscopy normal.
 VCE showed a few shallow ulcerations in the
mid ileum
 Double-balloon enteroscopy documented a few
ulcerations and biopsies showed only mild
nonspecific inflammation.
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Fecal Calprotectin Issues
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Def: A neutrophil-derived cytosolic protein released from
macrophages of inflamed bowel mucosa and shed into the
stool.
Has been proposed as a test to predict IBD relapse and to
differentiate functional and inflammatory bowel disorders.
Cost = $75.00-$500.00
Problems with sensitivity and cut-off values
How much of a difference is the test result going to make?
Patients with symptoms strongly suggestive of IBD should
directly undergo colonoscopy and ileoscopy, but other patients
could undergo fecal calprotectin screening, with results guiding
the need for endoscopy. (Rex D Journal Watch 2014)
The Problems with Serum Levels and
Antibodies to IFX/ADA
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Expensive
No clear society or governmental guidelines
that advocate using this testing
Testing has not been standardized in the daily
routine
Results of studies have not been uniform
Usefulness of Anser IFX/ADA
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Trough level of infliximab concentration of >3 µg/ml
was predictive of significantly lower disease activity
Induction phase - increasing the infliximab dose in CD
patients with suboptimal drug levels (<3 µg/ml) is
beneficial
Dose de-escalation in CD patients can be undertaken at
supra-optimal drug levels (>7 µg/ml)
Presence of antibodies predicts losing therapeutic
response
Individualised therapy is more cost-effective than dose
intensification in patients with Crohn's disease who lose response
to anti-TNF treatment: a randomised, controlled trial.
(Steenholdt et al. Gut 2014)
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IFX dose intensification (5 mg/kg every 4 weeks)
(n=36)
Interventions based on serum IFX and IFX
antibody levels using the proposed algorithm
(n=33)
Disease control, as judged by response rates, was
similar: 58% and 53%,
Treatment costs were lower (56%) in the algorithmtreated group (€ 4062 vs € 9178, p<0.001)
If you are going to use this testing:
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Be sure to inform your patient that the test may not
be covered and that they may need to make an appeal
to their insurance carrier
Make sure that the blood is drawn just prior to their
next drug dose (trough level)
I would not relinquish the appeal process to the
Prometheus company
Be familiar with numerous studies to show this
testing is useful in patients who may be losing
response to therapy
Case
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64-yo female with pan ulcerative colitis. Failed
azathioprine, MTX. Infliximab initiated 7 years ago
5 mg/kg and excellent response.
Began to have symptoms at week seven post
infusion 18 months ago and dosing was changed to
every 6 weeks with excellent response.
Last month began to experience symptoms 4 weeks
post infusion.
Could dose escalate or obtain IFX level and antibody
Case - cont’d
IFX level was undetectable
 IFX antibody level was 78 ng/ml
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Switched to adalimumab and doing well at this
time.
Alternative Biologics
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Xeljanz - inhibitor of Janus kinase (JAK
inhibitor) indicated for the treatment of RA
Actemra (tocilizumab) is an interleukin-6 (IL6) receptor antagonist indicated for the
treatment of RA
Stelera (ustekinumab) human interleukin-12
and -23 antagonist (approved for Crohn’s on
09/26/16, but not for top-down therapy)
The Appeal Process
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1st Level - Internal company review
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2nd Level - Patient must request. Will be
reviewed by Ins. medical director or company
may hire an outside consultant
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3rd Level - Patient must request. Mandated
external review by independent consultant or a
panel of 3 independent consultants.
How does this work in PA?
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1st Level - Company has 30 days to act with
an additional 5 days for communication
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2nd Level - Company has 45 days to act with
an additional 5 days for communication
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3rd Level - Patient must request within 15 days
of 2nd Level denial. Cost is $25.00. Decision
must be made within 60 days
2001 PA Review Data
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N = 6320 appeals
37% overturned on 1st Level appeal
13% went to 2nd Level appeal: 43% overturned
3rd Level appeal N=165: 42% overturned.
Personal Review Data 1990-2014
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N = 5820 reviews
52.3 % Upheld denial
 47.7% Overturned denial
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How to Navigate a Denial:
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Patient must appeal
Make sure that you are providing reasonable
and standard of care
Use language from plan’s definition of
medically necessary care
Be available to discuss case with medical
director or external reviewer (your personal cell
number is the easiest)
Plan Language of Medical Necessity:
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Varies from plan to plan
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Adequate scientific evidence to show that the
service is safe and effective
Not subject to IRB approval
Not undergoing clinical phase I, II, or III
clinical studies
Approved by the FDA
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Other Resources that can Assist in the
Appeal Process:
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Specialty Pharmacies
Pharmaceutical manufacturers
Reimbursement hubs (organizations recruited
by pharmaceutical manufacturers that
specialize in maximizing patient access)
The Crohn’s & Colitis Foundation of America
www.ccfa.org/science-andprofessionals/programs-materials/appealletters/
Dear Sir or Madam:
I am writing this letter in regards to my patient, PATIENT NAME, who I follow at LOCATION for care of his Crohn’s
disease/ulcerative colitis. I am requesting that he/she be able to have laboratory studies for serum infliximab and human antichimeric antibody (HACA) levels (CPT code 83520) at LOCATION, USA.
Mr./Ms./Mrs. NAME has lost response to infliximab. I would like to check infliximab and HACA levels to help guide further
therapy. These levels will help to determine if he/she needs increased frequency of infliximab or a change in therapy.
Please call my office at Phone Number, if you have any further questions.
Kind regards,
SIGNATURE
In Summary
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Lots of restrictions out there and I suspect this
will not get better in the future.
Adhere to practice guidelines
When practicing out of the box, have the
literature to back you up
Be familiar with the appeal process
Be available for case discussion with the reviewer