Now screening sits at the center of this dementia and brain health question.
Doctors are now screening for latent tuberculosis, hepatitis B, hepatitis C, and several other infections before prescribing any biologic medication — because these powerful drugs suppress specific arms of the immune system and can reactivate dormant pathogens with devastating consequences. The numbers tell the story plainly: patients treated with anti-TNF-alpha biologics face a 14-fold increased risk of tuberculosis reactivation compared with healthy individuals, and only 40 percent of patients who experienced hepatitis B reactivation had actually been screened beforehand. That screening gap has driven every major medical society — from the American College of Rheumatology to the American College of Gastroenterology — to mandate pre-biologic testing protocols.
For anyone navigating a new biologic prescription for conditions like rheumatoid arthritis, psoriasis, or inflammatory bowel disease, understanding what these screenings involve is not optional information. A person with a latent TB infection that goes undetected could develop active tuberculosis within weeks of starting a TNF inhibitor — a scenario that is both dangerous and entirely preventable with a simple blood test. This matters for brain health, too: systemic infections and the inflammatory cascades they trigger are increasingly linked to cognitive decline, and biologics themselves are under study for neuroinflammatory conditions. This article covers the specific tests doctors order before writing that first biologic prescription, why tuberculosis screening sits at the top of the list, what hepatitis screening now looks like under updated 2025 guidelines, the nine standard lab tests in a pre-biologic panel, known limitations of current screening tools, and what happens when these screenings reveal a problem.
Table of Contents
- Why Are Doctors Screening for Infections Before Prescribing Biologics?
- What the Standard Pre-Biologic Screening Panel Includes
- Tuberculosis Screening — Why It Tops the List
- Hepatitis B and C Screening Under the 2025 Guidelines
- Known Limitations of Current Screening Methods
- How Electronic Health Records Are Closing the Screening Gap
- What This Means for Patients With Neurological and Cognitive Conditions
- Conclusion
- Frequently Asked Questions
Why Are Doctors Screening for Infections Before Prescribing Biologics?
Biologics work by targeting precise components of the immune system — TNF-alpha, interleukins, or JAK pathways — that drive chronic inflammation. The trade-off is that these same pathways also keep dormant infections in check. Shut down TNF-alpha signaling, for instance, and a tuberculosis infection that has been quietly contained by the immune system for decades can roar back to life. this is not a theoretical risk. TB incidence among patients on biologics ranges from 172 to 457 per 100,000 patient-years in areas with moderate to high TB prevalence, figures that dwarf background rates in the general population. The screening mandate did not appear overnight.
It grew out of early post-marketing surveillance in the late 1990s and early 2000s, when the first wave of TNF inhibitors — infliximab, etanercept, adalimumab — revealed clusters of reactivated TB and hepatitis B in patients who had no idea they carried these infections. The American College of Rheumatology, the American Academy of Dermatology, the American College of Gastroenterology, and the European Crohn’s and Colitis Organisation all now recommend screening for TB, hepatitis B, and hepatitis C before starting biologic therapy. The goal is straightforward: find the infection before the biologic finds it first. Compare this to how doctors prescribed earlier immunosuppressants like methotrexate or azathioprine. Those drugs suppressed the immune system broadly, and while infection risk existed, it was less targeted. Biologics, by knocking out a single cytokine pathway, create a very specific vulnerability. A patient on a TNF inhibitor is not broadly immunocompromised the way a transplant patient on cyclosporine might be — but their risk for particular infections, especially intracellular pathogens like TB, is sharply elevated.
What the Standard Pre-Biologic Screening Panel Includes
The current standard of care calls for nine key tests before a patient starts any biologic, according to rheumatology practice guidelines. These include a complete blood count, liver function tests, a TB test using either a tuberculin skin test or interferon-gamma release assay, a hepatitis B panel, hepatitis C antibody screening, an HIV test, a pregnancy test, a varicella immunity check, and baseline immunoglobulin levels. Labcorp has formalized this into a single orderable panel — their Pre-Biologic Screening Profile, test number 144441 — which bundles these tests into one draw so nothing gets missed. Each test serves a specific purpose. The complete blood count establishes a baseline because biologics can cause blood abnormalities that may later require dose reduction or discontinuation. Liver function tests matter because if liver enzymes come back at 1.5 to 3 times the upper limit of normal, doctors may reduce dosing frequency; if they are higher than that, the biologic may be contraindicated entirely.
The varicella check might seem odd for an adult, but a biologic patient who contracts chickenpox or develops shingles without prior immunity faces serious complications. However, having a standardized panel does not mean every patient gets every test. In real-world practice, screening compliance has been inconsistent. A 2023 study found that implementing a Best Practice Advisory in electronic health records — essentially an automated alert that fires when a clinician prescribes a biologic without documented screening — significantly improved compliance. The fact that hospitals needed to build automated alerts into their prescribing software tells you how widespread under-screening had become. If your doctor orders a biologic and does not mention blood work first, that is worth asking about directly.
Tuberculosis Screening — Why It Tops the List
Tuberculosis gets top billing in pre-biologic screening because the numbers are stark. Between 10 and 17 percent of patients with immune-mediated inflammatory diseases are diagnosed with latent TB infection when they begin the screening process for biologic therapy. Most of these patients had no symptoms and no idea they carried the bacteria. Without screening, they would have started a biologic, and the drug’s suppression of TNF-alpha — the very cytokine that helps wall off TB granulomas — could have allowed the bacteria to disseminate. The screening itself involves either a tuberculin skin test or an interferon-gamma release assay, plus a chest X-ray. The ACR guidelines are specific about what happens next: if latent TB is detected, the patient must begin TB medication and remain on it for at least one month before the biologic can be started.
This delay frustrates patients who are dealing with painful, debilitating inflammatory conditions and want relief now. But the alternative — active TB in an immunosuppressed patient — is far worse and far harder to treat. Not all biologics carry equal TB risk. The highest reactivation risk is associated with TNF inhibitors and JAK inhibitors, and the danger compounds when these agents are combined or used sequentially with other immunosuppressive medications. A patient who takes a TNF inhibitor alongside methotrexate, for example, faces a greater TB reactivation risk than someone on the biologic alone. This is why rheumatologists track not just the current prescription but the full immunosuppressive history.
Hepatitis B and C Screening Under the 2025 Guidelines
The 2025 American Gastroenterological Association clinical practice guidelines expanded hepatitis B screening to require three specific markers — HBsAg, anti-HBs, and total anti-HBc — before initiating any immunosuppressive therapy. This aligns with CDC universal hepatitis B screening recommendations and represents a shift from earlier, less comprehensive panels. The reason for this expansion is a grim statistic: only 40 percent of patients who experienced hepatitis B reactivation during immunosuppressive therapy had been properly screened for HBsAg and anti-HBc beforehand, and only 10 percent had received prophylactic antiviral treatment. Hepatitis B reactivation is not a minor complication. When the virus reactivates in an immunosuppressed patient, it can cause fulminant hepatic failure.
Immune checkpoint inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, and CAR-T cell therapies are all classified as high risk for hepatitis B reactivation in patients who are HBsAg-positive. For patients found to carry hepatitis B markers, prophylactic antiviral therapy can be started alongside the biologic, but this requires knowing the status in the first place — which circles back to the screening gap. Hepatitis C screening follows a simpler protocol: a hepatitis C antibody test with reflex HCV RNA testing if the antibody comes back positive. The clinical calculus is different from hepatitis B because hepatitis C can now be cured with direct-acting antiviral regimens, so a positive result does not necessarily preclude biologic use — but it does change the treatment sequence and monitoring plan. The key tradeoff is timing: curing hepatitis C first delays biologic therapy, but starting the biologic first in a patient with active viremia risks liver complications during treatment.
Known Limitations of Current Screening Methods
Screening is not foolproof, and clinicians working with immunosuppressed patients know that the standard TB tests have significant blind spots. The tuberculin skin test is notably less accurate in patients who are already on immunosuppressive medications. Research shows a positivity rate of only 35.1 percent in immunosuppressed patients compared to 42.5 percent in untreated patients — meaning the skin test misses a meaningful number of infections in exactly the population where missing them matters most. This is why current guidelines increasingly recommend dual testing strategies, using both the TST and an IGRA, to reduce false negatives. The IGRA is generally considered more reliable in immunosuppressed patients because it measures a specific immune response to TB antigens in a blood sample rather than relying on a skin reaction that requires an intact cell-mediated immune response. But no test is perfect.
Indeterminate IGRA results occur more frequently in immunocompromised individuals, and repeat testing, chest imaging, and clinical judgment all play a role in the final assessment. A negative result in a patient with significant TB risk factors — born in a high-prevalence country, history of incarceration, healthcare work — may still warrant additional evaluation. There is also the problem of timing. Screening captures a snapshot. A patient who tests negative for TB or hepatitis B before starting a biologic can acquire these infections afterward, particularly if they travel internationally or have ongoing exposure risks. Annual rescreening is recommended in some guidelines for patients on long-term biologic therapy, but adherence to rescreening protocols is even less consistent than initial screening compliance.
How Electronic Health Records Are Closing the Screening Gap
The recognition that widespread under-screening was putting patients at risk prompted a practical intervention: building screening reminders directly into prescribing workflows. A 2023 study demonstrated that a Best Practice Advisory embedded in electronic health records — triggered whenever a clinician attempted to prescribe a new biologic — significantly improved the rate of completed pre-biologic infection screening. The alert essentially blocks the prescription workflow until documentation of screening is entered, making it harder to skip the step inadvertently.
This approach addresses the most common reason screening gets missed: not malice or ignorance, but workflow complexity. A rheumatologist managing a patient with severe rheumatoid arthritis who has failed two previous medications is focused on choosing the right biologic, adjusting doses, managing expectations. The screening panel, while critical, is a procedural step that can fall through the cracks in a busy clinic. Automating the reminder removes the reliance on memory and habit.
What This Means for Patients With Neurological and Cognitive Conditions
The relevance of pre-biologic screening extends beyond rheumatology and gastroenterology clinics. Biologics are increasingly being studied and used in neurological conditions — from multiple sclerosis to emerging research on neuroinflammation’s role in Alzheimer’s disease and other dementias. As these drugs move into brain health applications, the same screening protocols apply.
A patient being considered for a biologic targeting neuroinflammation needs the same TB panel, the same hepatitis screening, and the same baseline blood work as a patient with Crohn’s disease. The stakes may be even higher in older adults, who represent the largest demographic affected by cognitive decline and dementia. Older patients are more likely to have been exposed to tuberculosis decades ago, more likely to carry hepatitis B from an era before universal vaccination, and more likely to have baseline liver or blood count abnormalities that complicate biologic use. As biologics enter the neurology toolkit, the screening conversation needs to follow — and patients and caregivers should be prepared to advocate for thorough testing before any new biologic prescription begins.
Conclusion
Pre-biologic screening exists because these drugs create targeted vulnerabilities in the immune system — vulnerabilities that dormant infections like tuberculosis and hepatitis B can exploit with serious, sometimes fatal, consequences. The 14-fold increase in TB reactivation risk with TNF inhibitors, combined with the finding that only 40 percent of patients who experienced hepatitis B reactivation had been properly screened, makes the case for thorough testing before the first dose. Updated 2025 AGA guidelines, standardized panels like Labcorp’s pre-biologic screening profile, and electronic health record alerts are all working to close the screening gap. For patients, the practical takeaway is direct: if a doctor prescribes a biologic without ordering blood work first, ask why.
Request a complete pre-biologic screening panel. Know that a positive TB or hepatitis B finding does not necessarily mean you cannot take the biologic — it means the infections need to be addressed first, which may add weeks to your timeline but could prevent a dangerous reactivation down the road. The screening is not a bureaucratic hurdle. It is, by every available measure, the step that makes biologic therapy safe enough to justify its remarkable benefits.
Frequently Asked Questions
How long does pre-biologic screening take?
Most screening panels can be completed with a single blood draw and a chest X-ray, with results typically available within a few days. However, if latent TB is detected, ACR guidelines require at least one month of TB treatment before the biologic can begin, which extends the timeline significantly.
What happens if I test positive for latent tuberculosis?
A positive TB screening does not disqualify you from biologic therapy. Your doctor will start you on TB medication — typically isoniazid or rifampin — and you will need to complete at least one month of treatment before the biologic is prescribed. The TB treatment course itself usually lasts several months and continues alongside the biologic.
Are some biologics safer than others regarding infection reactivation?
Yes. The highest TB reactivation risk is associated with TNF inhibitors and JAK inhibitors. Combined or sequential use of anti-TNF agents with other immunosuppressive medications increases the risk further compared to monotherapy. Your rheumatologist or prescribing specialist should factor your infection risk profile into the choice of biologic.
Do I need to be rescreened if I switch from one biologic to another?
Guidelines vary, but many specialists recommend rescreening when switching biologic classes, especially if time has passed since the original screening or if you have ongoing exposure risks for TB or hepatitis. Annual rescreening is recommended in some protocols for patients on long-term biologic therapy.
Why was my doctor not screening for this before?
Screening has been recommended since the early 2000s, but compliance was inconsistent. Studies found that only 40 percent of at-risk patients had been properly screened, which prompted the development of electronic health record alerts and standardized screening panels to close the gap. Updated 2025 guidelines have further expanded and formalized the requirements.
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