CPAP Module 23, Section 3: Rheumatology Case: High-Cost Biologic
MODULE 23: SPECIAL TOPICS & CASE SIMULATIONS

Section 3: Rheumatology Case: High-Cost Biologic

Constructing the long-form clinical narrative to justify a non-formulary agent when the formulary has been exhausted.

SECTION 23.3

Rheumatology Case: High-Cost Biologic

Weaving a multi-chapter story of treatment failure to prove medical necessity for the next, and often last, line of therapy.

23.3.1 The “Why”: The Formulary Ladder and the Refractory Patient

In the worlds of oncology and neurology, prior authorization often centers on proving a patient meets initial, highly specific diagnostic and biomarker criteria. In rheumatology, particularly for established rheumatoid arthritis (RA), the challenge is different. The diagnosis is often long-standing, and the question is not “What does the patient have?” but “What has been tried, why did it fail, and where do we go next?” This shifts your role from a data finder for a single event to a clinical biographer, tasked with reconstructing a patient’s entire therapeutic journey, sometimes spanning a decade or more.

Payers manage the high cost of RA biologics by creating a rigid, multi-tiered “formulary ladder.” This is step therapy on an epic scale. They don’t just require a failure of one or two agents; they demand a documented failure of multiple agents across different drug classes. A typical path might require failure of conventional synthetic DMARDs (csDMARDs) like methotrexate, followed by failure of one or two preferred TNF-alpha inhibitors (the most common biologic class), before they will even consider a biologic with a different mechanism of action (e.g., an IL-6 inhibitor, a JAK inhibitor, or a T-cell co-stimulation modulator). For the PA pharmacist, this means a request for a non-formulary, third-line biologic is not a single request; it is an assertion that the patient has climbed this entire ladder and fallen off every rung.

The patient in this scenario is often described as having “refractory RA.” Their disease has been resistant to multiple standard-of-care treatments. They are exhausted, in chronic pain, and facing the prospect of irreversible joint damage and disability. The non-formulary biologic their rheumatologist has prescribed is not a matter of preference; it is a matter of necessity, often representing one of the last available therapeutic options. The stakes are profoundly high.

Your job is to translate this long, frustrating clinical history into the structured, evidence-based language that a payer understands. You cannot simply state, “The patient has tried everything.” You must prove it. You must provide the names of the drugs, the dates of trial, the doses used, and, most critically, the objective, documented reason for discontinuation for each one. This requires an exhaustive, forensic review of the medical record, piecing together progress notes, lab results, and patient communications to build an unbreakable case. This simulation will teach you how to become that clinical biographer and build a successful appeal for a patient who has run out of options.

Retail Pharmacist Analogy: The “Vacation Override” on Steroids

A patient comes to your pharmacy on a Friday afternoon. “I’m going to Europe for a month,” she says, “and my doctor gave me 90-day prescriptions for my eight chronic medications, but my insurance will only approve a 30-day supply for all of them.” You know this drill: the classic “vacation override.”

You can’t just resubmit the claim. You need to engage in a multi-step appeal process. You call the payer’s help desk. The first agent tells you they can’t do anything; it has to be a pharmacist. You get transferred. You explain the situation. The pharmacist agent says, “Okay, I can do a one-time override, but I need you to fax me proof of travel for the patient.” This is the documentation requirement.

The patient, luckily, has her flight itinerary on her phone. She forwards it to your pharmacy’s email. You print it out. Now you have the evidence. But it’s not that simple. The payer’s system will only allow the override on one prescription at a time. You have to go through the process for each of her eight medications. For the lisinopril, you get the override. For the metformin, the system glitches and you have to call back. For the atorvastatin, the override goes through but the copay is wrong. For the levothyroxine, the agent questions if she can get it filled abroad (you have to explain why that’s not feasible).

You are not just making one request. You are building a comprehensive case for this patient’s entire regimen, drug by drug, tackling unique roadblocks for each one. You are telling a story: “This patient requires her continuity of care to be maintained during a prolonged, documented period of travel.” You must prove this story eight different times, providing the same core evidence (the flight itinerary) but navigating a different set of procedural hoops for each claim.

This meticulous, multi-part, and often repetitive process of proving the same underlying need (the “vacation”) across multiple individual challenges (each drug) is a direct parallel to a high-cost rheumatology appeal. You have one patient, but you must prove four or five distinct treatment failures. Each failure is its own “chapter” that requires its own specific evidence (labs, notes, dates), but they all must be compiled into a single, cohesive narrative to justify the final, non-formulary drug. You already possess the tenacity and procedural focus; this is just applying it to a clinical, rather than logistical, history.

23.3.2 The Case Presentation: Meet Ms. Reed

A denial for a high-cost biologic for a long-time rheumatology patient lands in your queue. The case has been initiated and denied, and now requires a formal appeal.

Patient Demographics

  • Name: Evelyn Reed
  • Age: 58 years old
  • Insurance: Unified Health Alliance PPO (Plan ID: UHA998B76)
  • Prescribing Physician: Dr. Sarah Chen, MD (Rheumatology)

The Submitted Prescription

  • Drug: Tocilizumab (Actemra)
  • Dose: 162 mg
  • Route: Subcutaneous (SC) Injection
  • Frequency: Every week
  • Diagnosis Code Attached: M05.79 – Rheumatoid arthritis with rheumatoid factor of multiple sites without organ or systems involvement

The denial letter from Unified Health Alliance is attached to the case file.

Denial Notification: Tocilizumab

Status: NOT APPROVED (NON-FORMULARY)

Reason for Denial: Tocilizumab (Actemra) is a non-formulary agent on the patient’s plan. Per Clinical Policy #RH-004, coverage for a non-formulary biologic for Rheumatoid Arthritis can only be considered when there is documented evidence of trial and failure or contraindication to the required number of formulary agents.

Formulary Requirements:

  • Step 1: Trial and failure of at least a 3-month course of methotrexate (unless contraindicated).
  • Step 2: Trial and failure of at least one other conventional synthetic DMARD (e.g., sulfasalazine, leflunomide).
  • Step 3: Trial and failure of at least TWO preferred formulary TNF-alpha inhibitors. Preferred TNF-alpha inhibitors are adalimumab and etanercept.

Action Required: The submitted documentation was insufficient to establish this history. To appeal, please provide a complete medication history with chart notes, labs, and imaging documenting the failure or contraindication to all required formulary agents.

23.3.3 The Mission: Mapping the Formulary Gauntlet

The denial lays out a four-drug gauntlet that Ms. Reed must have run. Your mission is to prove she ran it, documenting each stage of the race. You must pull up Policy #RH-004 to understand the fine print, specifically the payer’s definition of “failure.”

Unified Health Alliance Policy #RH-004: Biologic Therapies for RA

Definition of “Failure” for csDMARDs (e.g., Methotrexate, Sulfasalazine):

  • A) Lack of Efficacy: Failure to achieve low disease activity (e.g., CDAI score > 10, DAS28 > 3.2) after 3 months of therapy at a target dose.
  • B) Intolerable Adverse Effects: Discontinuation due to documented adverse effects (e.g., LFT elevation > 2x ULN, severe GI intolerance, bone marrow suppression).

Definition of “Failure” for Biologic DMARDs (e.g., Adalimumab, Etanercept):

  • A) Lack of Efficacy: Primary non-response (failure to achieve low disease activity after 3 months) or secondary non-response (loss of efficacy after an initial response) as measured by a validated tool (e.g., CDAI, DAS28).
  • B) Intolerable Adverse Effects: Discontinuation due to documented adverse effects (e.g., serious injection site reaction, recurrent infections, infusion reactions).
The Four-Part Evidence Checklist

This policy creates a very specific, multi-chapter story you need to tell. Each chapter needs its own set of evidence.

  • Chapter 1: The Methotrexate Failure. I need start/stop dates (min. 3 months) and objective proof of failure (high disease activity scores OR labs/notes documenting side effects).
  • Chapter 2: The Second csDMARD Failure. I need start/stop dates and objective proof of failure for another agent like sulfasalazine or leflunomide.
  • Chapter 3: The First TNF Inhibitor Failure (Adalimumab). I need start/stop dates and objective proof of failure (serial disease activity scores showing no improvement OR notes documenting side effects).
  • Chapter 4: The Second TNF Inhibitor Failure (Etanercept). I need start/stop dates and objective proof of failure, same as above.

Only after you have conclusively documented all four of these failures can you justify the medical necessity of the non-formulary tocilizumab.

23.3.4 The Investigation: A Decade in the EMR

Reconstructing this history will require a deep, chronological review of the EMR, focusing on the rheumatology notes and medication history. You are on an archaeological dig for the story of Ms. Reed’s disease.

Masterclass Table: Piecing Together the Treatment History of Ms. Reed
Chapter Evidence Source EMR Findings & Interpretation
1. Methotrexate “Medications” Tab & “Labs” Tab. Med History: Methotrexate 25 mg SC weekly. Start: July 2015. Stop: Nov 2017. (Duration: >2 years).
Lab History: Searching LFTs around Nov 2017 reveals: AST: 110, ALT: 125 (ULN ~40).
Note Corroboration: A rheumatology note from Nov 15, 2017 states: “Patient’s LFTs are now persistently >2.5x ULN. We will discontinue methotrexate due to hepatotoxicity.”
Conclusion: Failure due to intolerable adverse effect. CHECK.
2. Sulfasalazine “Medications” & “Notes” Tabs. Med History: Sulfasalazine 1g BID. Start: Dec 2017. Stop: April 2018. (Duration: ~5 months).
Note Corroboration: A note from April 20, 2018 states: “Ms. Reed has been unable to tolerate sulfasalazine, reporting severe nausea and abdominal cramping that has not improved over time. She remains in a state of high disease activity with a CDAI of 25. We will discontinue SSZ and proceed to biologic therapy.”
Conclusion: Failure due to both intolerance AND lack of efficacy. CHECK.
3. Adalimumab (Humira) “Medications” & “Notes” (Flowsheets). Med History: Adalimumab 40 mg SC every 2 weeks. Start: May 2018. Stop: June 2020. (Duration: 2 years).
Flowsheet/Notes Review: You must track the disease activity scores over time.
  • May 2018 (Baseline): CDAI = 25 (High)
  • Nov 2018: CDAI = 18 (Moderate)
  • May 2019: CDAI = 15 (Moderate)
  • May 2020: CDAI = 20 (Moderate-High)
Note Corroboration: A note from June 5, 2020 states: “Despite two years of adalimumab therapy, Ms. Reed has never achieved our goal of low disease activity. Her CDAI remains elevated at 20. This represents a primary non-response. We will switch to another TNF inhibitor.”
Conclusion: Failure due to lack of efficacy. CHECK.
4. Etanercept (Enbrel) “Medications” & “Notes.” Med History: Etanercept 50 mg SC weekly. Start: July 2020. Stop: Sept 2021. (Duration: 14 months).
Note Corroboration: A note from Sept 10, 2021 states: “Patient initially had a good response to etanercept with CDAI improving to 8 (low disease activity). However, over the past 6 months she has experienced a gradual loss of response. Her CDAI today is back up to 19. This represents a secondary non-response. Having failed two TNF inhibitors, we must now switch to a different mechanism of action.”
Conclusion: Failure due to lack of efficacy (secondary non-response). CHECK.

23.3.5 The Master Appeal: Telling the Whole Story

You have now compiled all the evidence for four distinct treatment failures. The final step is to assemble this into a single, comprehensive appeal letter. This document is the culmination of your entire investigation and must be written with impeccable clarity and logic.

The Refractory RA Appeal Letter: A Comprehensive Narrative

SUBJECT: Appeal for Non-Formulary Agent Tocilizumab – Patient Evelyn Reed (ID: UHA998B76)

To the Medical Review Department,

This letter serves as a formal appeal for the coverage of tocilizumab (Actemra) for Ms. Evelyn Reed for the treatment of her refractory rheumatoid arthritis. Your denial indicated that the patient had not met the formulary requirements of trial and failure of two csDMARDs and two preferred TNF-alpha inhibitors, as per Policy #RH-004. The following detailed treatment history, with supporting documentation attached, will confirm that Ms. Reed has, in fact, exhausted all required formulary options and that the requested non-formulary IL-6 inhibitor is now medically necessary.

Documented History of Formulary Failures:

  1. Failure of csDMARD #1: Methotrexate
    Ms. Reed was treated with methotrexate from July 2015 to November 2017. Therapy was discontinued due to hepatotoxicity, as evidenced by LFTs persistently >2.5x the upper limit of normal.
    See Attached: Progress Note (11/15/2017) and Lab Report (11/14/2017).
  2. Failure of csDMARD #2: Sulfasalazine
    The patient was subsequently treated with sulfasalazine from December 2017 to April 2018. Therapy was discontinued due to a combination of intolerable GI side effects (severe nausea) and continued high disease activity (CDAI 25).
    See Attached: Progress Note (04/20/2018).
  3. Failure of TNF-Inhibitor #1: Adalimumab
    Ms. Reed was then advanced to biologic therapy with adalimumab from May 2018 to June 2020. This was discontinued due to primary non-response. Despite two years of therapy, she never achieved low disease activity, with her CDAI score remaining in the moderate-to-high range (final CDAI: 20).
    See Attached: Progress Note (06/05/2020) and CDAI Flowsheet.
  4. Failure of TNF-Inhibitor #2: Etanercept
    The patient was then trialed on a second preferred TNF inhibitor, etanercept, from July 2020 to September 2021. After an initial partial response, she experienced a secondary non-response (loss of efficacy), with her disease activity returning to a moderate level (final CDAI: 19).
    See Attached: Progress Note (09/10/2021).

Having failed four formulary agents across two different drug classes, including two preferred TNF-alpha inhibitors, Ms. Reed has exhaustively fulfilled the requirements of Policy #RH-004. Her disease is now considered refractory to TNF-inhibition. The clinical standard of care is to switch to a biologic with a different mechanism of action. Her rheumatologist has selected tocilizumab, an IL-6 inhibitor, as the most appropriate next step.

We respectfully request an authorization for tocilizumab to prevent further disease progression and irreversible joint damage for this patient with long-standing, difficult-to-treat rheumatoid arthritis. Thank you.

Sincerely,
[Your Name], PharmD
Prior Authorization Pharmacist