Meds & Biologics
If you have moderate-to-severe Crohn's disease and your doctor has mentioned biologics, you're facing a decision that didn't exist a generation ago. The number of approved biologics and targeted therapies has expanded rapidly, and in 2025, updated ACG clinical guidelines moved away from the old step-up model, allowing doctors to start advanced therapy earlier for the right patients. That's good news. But it also means you may be comparing drugs across multiple mechanism classes without a clear, drug-agnostic breakdown. Here's what you need to know.
How Biologics for Crohn's Disease Work, by Class
Every biologic targets a specific part of the inflammatory pathway. Understanding which part helps explain why one drug might suit your situation better than another.
Anti-TNF agents (infliximab/Remicade, adalimumab/Humira, and their biosimilars) block tumor necrosis factor-alpha, a protein that drives inflammation. These were the first biologics approved for Crohn's and have the longest track record. They remain the standard of care for perianal fistulizing disease, where infliximab and adalimumab have shown significant fistula closure rates. If you have fistulizing Crohn's, this distinction matters: anti-TNF agents have the strongest evidence for that phenotype.
Anti-integrin agents (vedolizumab/Entyvio) block alpha-4-beta-7 integrin, preventing inflammatory cells from migrating to the gut. Because vedolizumab acts primarily in the gut rather than systemically, it carries a favorable safety profile. However, it tends to work more slowly and has limited evidence for perianal fistulizing disease.
Anti-IL-12/23 agents (ustekinumab/Stelara) block both interleukin-12 and interleukin-23. The SEAVUE trial showed comparable remission rates to adalimumab at one year, with roughly two-thirds of patients achieving remission on either drug.
Anti-IL-23 agents (risankizumab/Skyrizi) target only IL-23, and recent head-to-head data has been striking. In the SEQUENCE trial, Skyrizi doubled the endoscopic remission rate compared to Stelara at week 48 (32% vs. 16%), while clinical remission rates favored Skyrizi 61% to 41%. A 2025 network meta-analysis ranked risankizumab as the top therapy for patients with prior anti-TNF exposure.
JAK inhibitors (upadacitinib/Rinvoq) are small molecules, not technically biologics, but they're part of the same treatment conversation. Rinvoq is approved for Crohn's patients who have had an inadequate response to anti-TNF therapy. Real-world data show 52% clinical remission at 12 weeks and 43% endoscopic remission at 6 months. Because it's an oral pill rather than an injection or infusion, some patients prefer the convenience, though it carries specific safety considerations including increased infection risk.
What "Best" Means Depends on Your Disease
There is no single best biologic for Crohn's. The right choice depends on disease behavior, location, prior treatment history, and personal factors like how you feel about injections versus infusions.
For biologic-naive patients, a systematic review found infliximab 5 mg/kg ranked highest for both induction and maintenance of clinical remission, with infliximab combined with azathioprine ranking first overall at 93.2%. For patients who have already tried an anti-TNF and lost response, risankizumab currently has the strongest positioning in the evidence.
For fistulizing perianal Crohn's, anti-TNF agents remain first-line. If anti-TNF treatment fails in this setting, ustekinumab and risankizumab are emerging options, while vedolizumab has shown limited efficacy for fistula closure.
When to Optimize vs. When to Switch
Losing response to a biologic is common, and the decision between dose escalation and switching depends on why the drug stopped working. This is where therapeutic drug monitoring (TDM) becomes essential. TDM measures your drug trough levels and checks for anti-drug antibodies through a blood draw, typically timed right before your next dose.
The results point to a clear decision tree. If your drug levels are low and you have no antibodies, dose escalation is the logical next step. If you have high antibody levels and undetectable drug, the antibodies are clearing the medication and switching is necessary. If your drug levels are adequate but you still have active inflammation, the drug's mechanism isn't controlling your disease, and switching to a different mechanism class is warranted.
About 50% of secondary non-responders re-enter remission with dose escalation alone, so optimizing before switching can save you from burning through treatment options prematurely.
Biosimilars Are Clinically Equivalent
If your insurance or pharmacy switches you from brand-name Remicade or Humira to a biosimilar, the evidence is reassuring. A meta-analysis of over 10,800 IBD patients found that biosimilars maintain comparable clinical remission rates, safety profiles, and immunogenicity to the originator drugs. Long-term data on adalimumab biosimilar switching show treatment persistence equivalent to staying on the original.
Realistic Timelines for Response
Anti-TNF agents can produce noticeable symptom improvement within the first few weeks, though full response may take up to 8 weeks. Vedolizumab works more gradually, with guidelines recommending reassessment at week 14 if there's no improvement. Risankizumab and ustekinumab typically show initial response by week 12, with endoscopic improvements continuing through week 48.
The critical point: symptom improvement alone doesn't confirm the drug is working. Endoscopic healing, confirmed by colonoscopy or imaging, is the target. Feeling better while still having active mucosal inflammation means the disease is progressing, even if you can't feel it yet.
Making Your Decision
Ask your gastroenterologist about your specific disease phenotype, whether TDM will be part of your monitoring plan, and what the switching strategy looks like if your first biologic doesn't hold. If you're starting or switching a biologic, tracking your symptoms from day one gives you and your doctor clear before-and-after data. A record of when improvements plateau helps evaluate whether you're in a true response or approaching the point where optimization or switching should be discussed.