Medication Elimination in Autoimmune Disease Following a Root-Cause Functional Medicine Program

Background. Autoimmune diseases are chronic, immune-mediated conditions for which conventional standard of care is designed to suppress symptoms and slow progression rather than to reduce or withdraw pharmacotherapy. Sustained medication discontinuation is therefore not an established goal or expected outcome of usual care.

Methods. We conducted a retrospective chart review of 22 patients with autoimmune disease enrolled in a root-cause functional medicine program at Root Functional Medicine and followed over a 12-month period. The primary outcome was complete elimination of at least one autoimmune medication. Because conventional care does not aim for and rarely achieves spontaneous discontinuation, the null (expected) elimination rate was set conservatively at 2%. Statistical significance was assessed using an exact one-sided binomial test. All medication discontinuations were physician-supervised, undertaken in coordination with each patient’s prescribing clinician, and were initiated only after the patient had achieved symptomatic remission.

Results. 6 of 22 patients (27.3%; 95% CI 10.7–50.2%) eliminated one or more autoimmune medications. Discontinued agents included guselkumab (Tremfya), apremilast (Otezla), etanercept (Enbrel), and dupilumab (Dupixent). Against the 2% null rate, this result was highly statistically significant (exact one-sided binomial p ≈ 0.0000036; p < 0.001).

Conclusions. In this retrospective cohort, a root-cause functional medicine program was associated with a medication-elimination rate roughly thirteen-fold higher than a conservative usual-care benchmark, a difference that is highly unlikely to be due to chance. Given the recurring annual cost of the biologic and oral immunomodulator therapies discontinued, the economic return on medication reduction alone was substantial. 

Autoimmune diseases affect an estimated 24–50 million Americans and represent one of the largest and fastest-growing categories of chronic disease cost in the United States. Direct treatment costs across the more than 100 recognized autoimmune conditions are estimated at upwards of $100 billion per year, with broader estimates exceeding $200–300 billion when indirect costs are included.¹ʲ² Per-patient annual costs for common immune-mediated conditions — including rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, and inflammatory bowel disease — commonly range from roughly $12,000 to $53,000.³

These conditions are chronic and, by conventional definition, incurable. The therapeutic goal of standard of care is disease control: reducing inflammation, managing symptoms, and slowing progression, typically through indefinite use of immunomodulators and biologic agents.⁴ Biologic and targeted oral therapies such as etanercept, guselkumab, apremilast, and dupilumab are frequently prescribed for lifelong use, and their list prices commonly run into the tens of thousands of dollars per patient per year.⁵⁻⁸ Critically, conventional treatment protocols do not set sustained medication withdrawal as an explicit objective, and durable, fully treatment-free remission is uncommon and not an expected outcome of usual care. This provides the rationale for using a very low expected (null) elimination rate as the comparator in this analysis.

This was a retrospective chart review of 22 patients with physician-diagnosed autoimmune disease who enrolled in a root-cause functional medicine program at Root Functional Medicine. All patients were receiving one or more autoimmune medications at baseline. Patients were followed over a 12-month observation period. The study used a single-arm design; no concurrent internal control group was enrolled.

The primary outcome was complete elimination of one or more autoimmune medications during the observation period, as documented in the medical record. "Elimination" was defined as full discontinuation of the agent (not merely dose reduction). Critically, deprescribing in this cohort was clinician-directed: in every case the medication was tapered and discontinued under the supervision of the patient’s prescribing physician, and discontinuation was initiated only after the patient had achieved symptomatic remission. No medication was stopped abruptly or in the presence of active disease, and the decision to withdraw therapy was made by the treating physician and patient in shared medical decision making.

Because conventional standard of care does not aim for medication elimination and spontaneous, sustained discontinuation is rare, the expected (null) elimination rate was set at a conservative 2%. We deliberately used a small non-zero rate rather than 0% so that the test remains statistically valid and the resulting estimate is conservative. The observed proportion was compared against this null using an exact one-sided binomial test (H₀: p ≤ 0.02; H₁: p > 0.02). The 95% confidence interval for the observed proportion was calculated using the exact (Clopper–Pearson) method. A two-sided alpha of 0.05 was considered the threshold for significance.

Of the 22 enrolled patients, 6 eliminated at least one autoimmune medication during the 12-month period, for an observed elimination rate of 27.3% (95% CI 10.7–50.2%). Under the 2% null rate, the expected number of eliminations among 22 patients would be approximately 0.44; the observed count of 6 falls far in the upper tail of the null distribution.

 | Measure | Value
| Patients enrolled (Root arm) | 22
| Patients eliminating ≥1 medication | 6
| Observed elimination rate | 27.3%
| 95% confidence interval (exact) | 10.7% – 50.2%
| Null / usual-care benchmark rate | 2%
| Expected eliminations under null | 0.44
| Exact one-sided binomial p-value | p ≈ 0.0000036  (p < 0.001)
| Statistically significant at α = 0.05 | Yes — highly significant

 

The exact one-sided binomial p-value of approximately 0.0000036 indicates that, if the true elimination rate were only 2%, observing 6 or more eliminations among 22 patients would occur by chance roughly 4 times in a million. The result is therefore highly statistically significant, and the null hypothesis is rejected.

The following autoimmune agents were fully discontinued among the responders. All are chronic-use immunomodulatory or biologic therapies that are otherwise typically continued indefinitely.

 | Brand | Generic | Class | Approx. annual list cost*
| Tremfya | guselkumab | IL-23 inhibitor (biologic) | ~$90,000
| Enbrel | etanercept | TNF-α inhibitor (biologic) | ~$84,000
| Otezla | apremilast | PDE4 inhibitor (oral) | ~$67,000
| Dupixent | dupilumab | IL-4/IL-13 inhibitor (biologic) | ~$48,000

Eliminating a chronic autoimmune medication produces recurring annual savings for as long as the patient remains off therapy. Using the approximate annual list costs above, the average annual drug cost avoided per eliminated medication is roughly $72,250 (mean of the four agents discontinued).

Two complementary ROI perspectives are presented. The cohort-level figure is the more conservative and is recommended as the headline metric, because it accounts for the program cost of all 22 enrolled patients — including those who did not eliminate a medication — against the savings generated by the 6 who did.

 | Cohort-level ROI  | Value (first year)
| Annual drug cost avoided (6 × ~$72,250) | ~$433,500
| Program cost 500 person company | $180,000
| Net first-year benefit | ~$253,500
| Return on investment (ROI) | ~141%  (≈ 2.4× return)

 

This first-year return is conservative on several counts. The $180,000 program cost covers all 500 employees — including the large majority without autoimmune disease — while the savings counted here come only from the 6 autoimmune-medication eliminations. No credit is taken for benefits in cardiometabolic, gut, musculoskeletal, or other domains the program also addresses. And because biologic therapy is typically lifelong, these drug savings recur every year a patient remains off medication, so the multi-year return compounds well beyond the first-year figure shown.

First-year ROI from autoimmune medication reduction alone, for a 500-employee company at varying per-employee program costs (annual drug savings held at ~$433,500):

 | Per-employee program cost | Total program cost (500 employees) | First-year ROI (autoimmune Rx savings only)
| $240 | $120,000 | ~261%
| $360 | $180,000 | ~141%
| $480 | $240,000 | ~81%
| $600 | $300,000 | ~45%

Even at $600 per employee per year ($300,000 for a 500-person company), medication reduction alone delivers a positive first-year return (~45%) — before counting any savings in office visits, hospitalizations, monitoring, or indirect (productivity) costs, or any benefit beyond autoimmune disease.

In this retrospective cohort, 27.3% of patients eliminated at least one autoimmune medication over 12 months — an outcome that is not an established goal of conventional care and that occurs rarely under usual treatment. The exact binomial analysis indicates the result is highly unlikely to reflect chance (p < 0.001) relative to a conservative 2% benchmark. The clinical relevance is reinforced by the specific agents discontinued: high-cost biologics and targeted oral immunomodulators ordinarily continued indefinitely. The associated economic return from medication reduction alone is substantial and recurs annually.

·       Retrospective, single-arm design without a concurrent internal control group; the 2% comparator is derived from the nature of standard of care rather than a matched cohort.

·       Small sample (n = 22). While the result is statistically significant, the 95% confidence interval is wide (10.7–50.2%), so the point estimate should be interpreted with caution.

·       Cost and ROI figures use list/WAC drug prices and an assumed program cost; actual net savings depend on payer, rebates, and Root’s real pricing.

A root-cause functional medicine program was associated with a statistically significant and clinically meaningful rate of autoimmune medication elimination, with a strong economic return from drug-cost avoidance alone. These hypothesis-generating findings support the design of a prospective, controlled study with a larger sample, predefined durability endpoints, and validated disease-activity and safety measures.

1.  Autoimmune Association. The Economic Effects of Autoimmune Disease. autoimmune.org/advocacy/economic-effects-of-autoimmune-disease-research/

2.  HCPLive. Autoimmune Diseases Cost US More Than $100 Billion Annually. hcplive.com/view/autoimmune-diseases-cost-us-more-than-100-billion-annually

3.  Dr. Bonnie 360 / Autoimmune Connect. The Total Cost Burden of the Autoimmune Epidemic (2023). drbonnie360.com/2023/03/22/the-total-cost-burden-of-the-autoimmune-epidemic/

4.  Deloitte. Autoimmune Diseases: Diagnoses, Prevalence, and Treatments. deloitte.com/us/en/Industries/life-sciences-health-care/blogs/health-care/autoimmune-diseases-diagnoses-prevalence-and-treatments.html

5.  Enbrel (etanercept) pricing — CMS Medicare negotiated price effective Jan 2026 and list pricing. See PMC: "The Inflation Reduction Act and Etanercept," pmc.ncbi.nlm.nih.gov/articles/PMC12401810/; GoodRx, goodrx.com/enbrel.

6.  Tremfya (guselkumab) list pricing, 2025. GoodRx, goodrx.com/tremfya/how-much-is-tremfya-without-insurance; Drugs.com, drugs.com/price-guide/tremfya.

7.  Otezla (apremilast) list pricing (WAC ~$5,590/30-day supply), 2025–2026. Healthline, healthline.com/health/drugs/otezla-cost; CADTH/NCBI, ncbi.nlm.nih.gov/books/NBK518589/.

8.  Dupixent (dupilumab) list pricing (~$3,993/month), 2025. SingleCare, singlecare.com/blog/dupixent-cost-per-month/; Drugs.com, drugs.com/price-guide/dupixent.