Pharmacogenetic testing for biologic medications? Myth vs reality

Ruslan Dorfman, PhD, MBA30 Oct 2026

The rising cost of biologic medications is a major concern for private and public drug plans. To manage these costs, some plan sponsors and providers are looking at genetic tests that claim to predict who will respond to a biologic. Others are switching patients from brand-name biologics to biosimilars. This article separates myth from reality: what genetic testing can and cannot do for biologics today, which approaches are proven, and where pharmacogenetic (PGx) testing, such as Pillcheck, adds real value for people with autoimmune and inflammatory conditions.

What are biologics and biosimilars?

Biologics are large, complex medications made in living cells, often antibodies that block a specific part of the immune system. They are used for conditions such as rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease (IBD, which includes Crohn's disease and ulcerative colitis), multiple sclerosis (MS) and many cancers. Examples include TNF blockers such as infliximab and adalimumab, IL-6 blockers and IL-17 and IL-23 blockers.

A biosimilar is a biologic that is highly similar to an original (reference) biologic, with no meaningful differences in safety or effectiveness. Unlike generic pills, biosimilars are not identical copies, because biologics are made in living cells. Most Canadian provinces now require many people on public drug plans to switch to biosimilars, starting with British Columbia in 2019, which has lowered costs without reducing effectiveness.

How does genetic testing guide cancer treatment?

In cancer, genomic testing is standard care. Many targeted cancer medications are designed to block a specific mutation that drives a tumour. A companion diagnostic test on the tumour, done by a specialized pathology laboratory, shows whether the patient is likely to benefit. Because a single tumour mutation can strongly predict response or resistance, this approach has improved outcomes and reduced unnecessary treatment.

Inherited (germline) gene variants also matter for some cancer medications:

DPYD controls the enzyme that breaks down fluorouracil (5-FU) and capecitabine, chemotherapy drugs widely used for colorectal, breast and other cancers. People with reduced or absent DPYD activity can develop severe or even fatal side effects at standard doses. CPIC recommends a lower starting dose for those with reduced activity and a different drug for those with no activity. Important variants include *2A, *13, c.2846A>T and HapB3, and c.557A>G, which is more common in people of African ancestry.
UGT1A1 affects how the body clears irinotecan, and people with reduced UGT1A1 activity have a higher risk of severe side effects.

Can genetic tests predict response to biologics for autoimmune diseases?

Not yet. Autoimmune diseases are caused by complex interactions among hundreds of genetic and environmental factors. Hundreds of gene variants have been linked to response to biologics in research studies, but each has a small effect, and even combinations of them cannot reliably predict who will respond. No validated companion test exists to choose a biologic for RA, IBD, psoriasis or MS.

Using unvalidated tests to choose or deny a biologic can harm patients. Treatment delays in these conditions can lead to joint damage, surgery or disability.

One promising research finding concerns HLA-DQA1*05, an immune gene variant carried by about 40% of people of European ancestry. In a large UK study of people with Crohn's disease, carriers developed antibodies against infliximab and adalimumab about twice as often, which can make these medications stop working. A clinical trial is still needed to show whether testing before treatment improves outcomes. Pillcheck does not report HLA genes, because HLA results are easily misread and most tests check only a few of the thousands of HLA variants.

What does help predict response to biologics?

Therapeutic drug monitoring (TDM) measures the level of the biologic in the blood just before the next dose (the trough level) and checks for anti-drug antibodies. In IBD, guidelines support TDM when a TNF blocker such as infliximab or adalimumab stops working. A low drug level without antibodies suggests the dose should be increased or given more often. High antibody levels suggest switching to another medication. TDM applies to both original biologics and biosimilars.

Clinical monitoring of disease activity, using symptoms, blood tests such as C-reactive protein, stool tests in IBD and imaging, guides decisions to continue, adjust or switch treatment.

Where does pharmacogenetic testing help in autoimmune diseases?

Many people with autoimmune conditions also take non-biologic medications, where PGx testing is well established:

Azathioprine and mercaptopurine (thiopurines), widely used in IBD and other autoimmune conditions, are guided by the TPMT and NUDT15 genes. People with low or absent activity in either gene can develop severe, sometimes life-threatening, bone marrow suppression at standard doses. The Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends a lower starting dose or a different drug for them. NUDT15 variants are especially common in people of East Asian and Hispanic ancestry.
Oral JAK inhibitors, such as tofacitinib (Xeljanz) and upadacitinib (Rinvoq), are newer non-biologic tablets for RA, IBD and other conditions. Tofacitinib is broken down by CYP3A4 and CYP2C19, and its dose must be lowered with fluconazole or strong CYP3A4 blockers. Upadacitinib is broken down mainly by CYP3A4.
Medications for related conditions, such as pain relievers, antidepressants, acid reducers and blood thinners, are often affected by CYP2C19, CYP2D6, CYP2C9 and other genes.

Cancer	Autoimmune and inflammatory diseases (RA, IBD, psoriasis, MS)
Tests look for specific mutations in the tumour	Response depends on many immune genes and environmental factors
A single mutation can strongly predict response or resistance	Even combinations of gene variants cannot yet predict response to biologics
Genomic testing is standard care to guide therapy	No validated genetic test guides the choice of biologic
Response is monitored by imaging and circulating tumour DNA	Response is monitored by disease activity and, for some biologics, drug levels and anti-drug antibodies
Germline genes such as DPYD and UGT1A1 guide chemotherapy safety	TPMT and NUDT15 guide thiopurines, and CYP genes guide many non-biologic medications

Myth vs reality: what pharmacogenetic tests can and cannot do for biologic medications

What should plan sponsors know?

Biosimilar switching and drug-level monitoring are proven ways to manage biologic costs.
Be cautious with tests that claim to predict response to biologics for autoimmune diseases. They are not yet validated in clinical trials.
PGx testing is well established for many non-biologic medications, which make up most drug claims, and for thiopurines used in autoimmune disease. It can help reduce side effects and avoid medications that are unlikely to work.

How can a pharmacogenetic test help?

A Pillcheck test reports TPMT, NUDT15, DPYD, UGT1A1, CYP3A4, CYP2C19, CYP2D6, CYP2C9 and other genes that affect many non-biologic medications used by people with autoimmune and inflammatory conditions, as well as some chemotherapy drugs. For DPYD, Pillcheck reports the key variants recommended for testing, including *2A, *13, c.2846A>T, HapB3 and c.557A>G. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. A Pillcheck pharmacist reviews your results together with all your medications and gives recommendations to discuss with your doctor. Read more about how to get a pharmacogenetic test in Canada.

Summary

Genetic tests cannot yet predict who will respond to biologics for autoimmune diseases.
In cancer, tumour genomic testing is standard care for choosing targeted treatments, and DPYD and UGT1A1 testing helps make some chemotherapy safer.
Therapeutic drug monitoring and biosimilars are proven tools for using biologics well and managing cost.
HLA-DQA1*05 is linked to antibodies against anti-TNF drugs, but testing is not yet routine.
PGx testing is well established for thiopurines (TPMT, NUDT15), oral JAK inhibitor interactions and many other non-biologic medications.

Frequently asked questions

Can a DNA test tell me which biologic will work for my arthritis or Crohn's disease?

Not yet. No validated genetic test can predict response to biologics for these conditions. Your specialist will choose based on your disease, health history and, for some biologics, drug-level testing.

Are biosimilars as good as the original biologic?

Yes. Biosimilars are approved only after showing no meaningful differences in safety or effectiveness. Many Canadians have switched to biosimilars without loss of benefit.

Is Pillcheck useful if I take a biologic?

Pillcheck does not predict response to biologics. It is useful for the other medications you may take, such as azathioprine, JAK inhibitors, pain relievers, antidepressants and acid reducers.

Should I be tested for TPMT and NUDT15 before taking azathioprine?

Yes. Testing before starting azathioprine or mercaptopurine is recommended, because people with low activity in either gene need a much lower dose or a different medication.