For years, immunology has ranked as one of the top therapeutic areas by value, with year-over-year growth driven by blockbuster biologics for conditions like rheumatoid arthritis (RA), psoriasis, and inflammatory bowel disease (IBD). Now, a wave of therapies with novel mechanisms of action (MoAs) is expanding the immunology conditions that can be treated, even as biosimilars and Medicare price negotiation compress the value of legacy brands.
The top 20 immunology drugs generated roughly $81 billion in 2024, growing at nearly 9.4% a year. The broader immunology market reached about $112 billion in 2025, over half of it in North America. With oncology and antidiabetics, immunology accounts for two-thirds of all U.S. biologic spending.
No Specialty Costs Payers More — or Keeps Growing Faster
As a therapeutic area, immunology’s cost profile is distinctive, as it has a very high per-patient cost applied to large, chronic, and often lifelong populations. Inflammatory conditions have repeatedly been the single largest driver of commercial drug trend. As one large PBM noted, inflammatory drugs represented nearly a quarter of its total commercial drug spend in 2022.
Overall, specialty drugs represent roughly 2% of claims but about half of pharmacy spending, with the average specialty patient costing a plan around $38,000 a year versus a few hundred dollars for a non-specialty patient. To cite just one example of the cumulative effect on payers within immunology, Medicare spending on Stelara rose nearly tenfold from about $300 million to $3 billion between 2016 and 2023—for approximately 20,000 Part D members.
This immense financial pressure is precisely why immunology has become the prime target of biosimilars and Medicare price negotiation, both of which recently intensified. Humira and Stelara biosimilars each captured roughly a quarter of their molecule’s Part D volume in 2025, while Stelara and Enbrel became two of the first drugs to carry Medicare-negotiated prices, effective 2026. As a result, every new mechanism entering immunology is now judged as much on its access and value story as on its clinical data.
The Therapeutic Ceiling Is Driving Immunology Innovation
For years the standard of care across RA, psoriasis, psoriatic arthritis, and IBD centered on the TNF inhibitor class: AbbVie’s Humira (adalimumab), Amgen’s Enbrel (etanercept), Johnson & Johnson’s Remicade (infliximab), and UCB’s Cimzia (certolizumab pegol). J&J’s Stelara (ustekinumab), which targets the shared p40 subunit of IL-12 and IL-23, later became a second anchor, particularly in IBD.
Humira defined the category, becoming the first drug to generate more than $20 billion in annual global sales, at a U.S. list price of roughly $90,000. That dominance is now unwinding. After U.S. biosimilar entry in 2023, global Humira revenue fell to approximately $4.5 billion in 2025. Adalimumab now has at least 10 approved biosimilars, more than any other biologic, and Stelara biosimilars began launching in 2025.
The strategic lesson is one AbbVie executed deliberately: a legacy brand facing loss of exclusivity must have a next-generation franchise ready before the originator’s dominance declines. AbbVie’s successors to Humira, Skyrizi and Rinvoq, now generate more revenue than Humira ever did at its peak.
Beneath the revenue numbers lies a quieter and more consequential story. Despite more than a dozen advanced therapies now available in indications like IBD, clinical and endoscopic remission rates have stubbornly plateaued at roughly 30-40% at one year. Researchers increasingly describe this as a “therapeutic ceiling” — a limit on what blocking any single established cytokine can achieve. More than any pricing pressure, that ceiling is driving the next wave of innovation: new MoAs, new modalities, and a shift from chronic symptom suppression toward durable (and sometimes drug-free) disease control.
The New Mechanism Map: From TL1A to Immune Reset
The tidal wave of new immunology treatments splits into two segments. The first category is next-generation entrants in established classes, such as oral TYK2 inhibitors like zasocitinib (Takeda) and envudeucitinib (Alumis); these drugs are competing primarily on route and selectivity. The second category is comprised of therapies built on entirely new targets, including the following:
- TL1A, the most-watched new target. Antibodies that block TL1A (a signaling protein tied to both intestinal inflammation and fibrosis) have become the hottest area in immunology, with the fibrosis angle offering differentiation from incumbent anti-TNFs. Three are in or entering Phase 3 for ulcerative colitis and Crohn’s: Merck’s tulisokibart (acquired in its $10.8 billion Prometheus buyout), Teva and Sanofi’s duvakitug, and Roche’s afimkibart. Merck is already expanding tulisokibart into hidradenitis suppurativa, axial spondyloarthritis, and RA, showing the multi-indication potential of this new MoA.
- Oral IL-23, a new modality for an established target. In March 2026, J&J’s icotrokinra (Icotyde) gained FDA approval for plaque psoriasis, as the first oral peptide that blocks the IL-23 receptor. This drug delivers the efficacy of the dominant IL-23 biologic class in a once-daily pill, with no required lab monitoring. For payers who have long managed injectable biologics through step therapy, an oral with comparable efficacy changes both the access calculus and patient-preference dynamics.
- FcRn inhibitors, a new MoA for antibody-driven disease. Drugs that block the neonatal Fc receptor accelerate clearance of the pathogenic IgG antibodies that drive certain autoimmune conditions. Three are now approved for generalized myasthenia gravis: argenx’s Vyvgart (efgartigimod, 2021), UCB’s Rystiggo (rozanolixizumab, 2023), and J&J’s Imaavy (nipocalimab), approved in 2025. The class is expanding toward primary Sjögren’s disease and other rare, underserved IgG-mediated conditions.
- The type-2 umbrella and the horizon. Sanofi and Regeneron’s dupilumab (Dupixent) continues to prove that one MoA (IL-4/IL-13) can be monetized across many type-2 diseases, as this drug has become the first biologic for COPD as well as the first new chronic spontaneous urticaria therapy in a decade. Furthest out, CD19 CAR-T cell therapy, borrowed from oncology, is being tested as a one-time “immune reset” for lupus and other autoimmune diseases, a model that could upend chronic-biologic economics entirely.
New MoAs Face Lower Bar to Enter, but Higher Bar to Win
While new MoAs expand the top of the market, two forces are compressing the bottom. Biosimilars have moved from slow uptake to rapid, PBM-engineered erosion. Once the major PBMs granted them preferred status, adalimumab biosimilars took nearly 50% of eligible Humira prescriptions by the end of 2024, and the inflammatory-conditions trend fell for the first time in years.
Stelara biosimilars, launched in 2025, are likely to erode faster. At the same time, Medicare price negotiation is working through the immunology class in sequence, beginning with Enbrel and Stelara from 2026, Otezla from 2027, and Orencia, Xeljanz and Cimzia from 2028, with Rinvoq eligible next.
Payer sentiment reinforces this shift. In MMIT’s Q2 2026 Biologics & Injectables Index survey on immunology access management, 49% of payers named the clinical effectiveness of existing treatments a significant driver of unmet need. In fact, payers ranked the insufficient clinical efficacy of existing drugs well above cost, utilization management, or access barriers. Systemic lupus erythematosus topped the list of greatest unmet need, ahead of RA and IBD.
Crucially, a new MoA earns less formulary movement than a biosimilar. A biosimilar launch triggers swift repositioning as payers move to capture the discount, while a new MoA draws only measured, wait-and-see adjustments. In addition, payers are likely to get stricter over the next few years, as 51% expect a more restrictive immunology strategy with novel brands increasingly positioned behind biosimilars and established market leaders.
The Access Playbook for New Mechanisms and At-Risk Brands
For manufacturers of new MoAs, differentiation is everything. Payers will scrutinize whether a novel mechanism, an oral route, a longer dosing interval, or broader multi-indication coverage delivers value worth the price. They will compare new entrants directly against biosimilar and negotiated-price benchmarks. Head-to-head superiority data (as in AbbVie’s Rinvoq-versus-Humira trial, or icotrokinra’s trial against ustekinumab) and cost-offset evidence that ties a comparatively higher drug cost to reduced hospitalizations, disease progression, or downstream spend are increasingly the currency of access.
For legacy and at-risk brands, the defining lesson is to build the successor before the cliff. AbbVie still grew through roughly $16 billion of U.S. Humira erosion on the strength of Skyrizi and Rinvoq, and J&J is positioning Tremfya to absorb declining Stelara. Manufacturers should also re-engage payers with refreshed clinical and real-world evidence. In situations in which a biosimilar threatens an injectable, manufacturers should consider oral or longer-acting formulations to defend their market share.
Manufacturers should also lock in durable payer contracts ahead of the biosimilars cliff. According to our survey responses, traditional rebate agreements remain the dominant immunology contracting model, used by 77% of payers. Portfolio and outcomes-based contracts are each used by roughly a third of payers. At-risk brands have several levers to pull to hold their preferred position before lower-cost competition arrives.
Immunology will keep growing, but its value is quickly pivoting away from legacy TNF and first-generation biologics into new mechanisms, oral formats, and biomarker-defined populations. Biosimilars have already proven that this category’s spend curve can be bent—and the IRA shows that the government intends to keep bending it. The manufacturers who win will pair mechanistic differentiation with payer-ready value evidence that turns a novel MoA into a durable brand.
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