Can You Combine Biologics for Autoimmune Disease?
In patients with rheumatic conditions, the question sometimes comes up: Can we combine biologic drugs?
In general, we do not combine biologic medications in rheumatology. There are important reasons for this, particularly the potential for increased infection risk when we block multiple parts of the immune system at the same time.
But there are unique circumstances where we may thoughtfully and cautiously consider combining biologic therapies.
Psoriatic arthritis is one example.
Let me walk you through how I think about this, but first, let’s start with some basics.
What are biologic drugs?
Biologic drugs are immune-targeted molecules that target specific parts of the immune system. The goal is to get closer to the root cause of inflammation and treat the chronic inflammation associated with autoimmune and inflammatory diseases.
Unlike medications that broadly suppress the immune system, biologics are targeted medicines that block specific signals or pathways involved in the inflammatory process.
What diseases are biologic drugs used for?
Biologic medications are used to treat many different rheumatic and autoimmune diseases, including rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, Sjögren’s disease, systemic vasculitis, and many more.
The specific biologic we choose depends on the disease, the organs involved, the type of inflammation, previous treatments, other medical conditions, and the patient’s individual risk factors.
Why do we generally not combine biologic drugs?
We generally do not combine biologic drugs in rheumatology, primarily because of the potential increased risk of infection.
Biologics work by targeting specific parts of the immune system. When we block more than one immune pathway at the same time, we have to think carefully about whether we may be suppressing the immune system too much.
For decades, the standard approach has been to use one biologic at a time.
If it doesn’t work well enough, we generally switch to another biologic or another targeted therapy rather than simply adding a second biologic.
Why? Because more of the immune system you block at once, the more you have to consider the potential consequences, particularly infection risk.
Are there unique circumstances in rheumatology where we consider combining biologics?
In unique cases — which are the exception, not the rule — we sometimes cautiously consider combining biologic therapies.
Can you take two biologic medications at the same time?
In general, we don’t.
But in carefully selected patients with difficult-to-control psoriatic arthritis, there are circumstances where we may consider it.
Let’s discuss why, but first, what broad categories of biologics are used in psoriatic arthritis?
In psoriatic arthritis, the three big biologic targets include:
TNF — drugs like adalimumab, etanercept, infliximab, golimumab, and certolizumab
IL-17 — secukinumab, ixekizumab, and bimekizumab
IL-23 — guselkumab and risankizumab
Each of these works on a different “wire” in the inflammation circuit.
For decades, the standard rule has been: use one biologic at a time. If it doesn’t work well enough, you switch to another — you don’t stack them.
Again, that rule exists for a good reason: the more of the immune system you block at once, the more you worry about infections.
So when we talk about “combining” biologics or using “dual targeted therapy,” we mean deliberately using two biologics together — for example, a TNF blocker plus an IL-17 or IL-23 blocker — in someone whose disease just won’t come under control any other way.
Why would you combine a TNF inhibitor with an IL-17 or IL-23 inhibitor?
Psoriatic arthritis is really several problems wearing one name: swollen joints, spine and low-back inflammation, swollen “sausage” fingers and toes (dactylitis), inflammation where tendons attach to bone (enthesitis), plus skin and nail disease.
Sometimes different drugs are better at different pieces of that puzzle.
Here’s the frustrating part that drives the question: the different biologics tend to shine in different areas.
IL-17 and IL-23 blockers are often the strongest for clearing skin. TNF and IL-17 blockers tend to be workhorses for joints and spine disease.
So a patient can end up with great skin but stubborn joints, or vice versa.
That mismatch is exactly the situation where the idea of combining two mechanisms comes up.
What happens if one biologic controls my psoriasis but not my arthritis?
This is one of the most practical situations in which patients ask me about combination therapy.
You may have a medication that has done an excellent job controlling your psoriasis, but you are still having swollen joints, enthesitis, dactylitis, or inflammatory back pain.
The question then becomes: do we abandon a medication that is working well in one area and switch to something else, or can we keep what is working and add another targeted treatment?
That is where dual biologic therapy becomes an interesting — but still very individualized — conversation.
What does the research actually show about combining biologics?
I want to be straight with you: there are no large, gold-standard trials that were designed to test “TNF plus IL-17” or “TNF plus IL-23” as a combination.
What we have is smaller, real-world experience — helpful, but not the final word.
The most useful real-world report comes from a group of centers in Spain that treated patients with refractory disease using two targeted drugs at once. The most common pairings were a TNF blocker plus an IL-12/23 blocker, followed by a TNF blocker plus an IL-17 blocker.
Among these hard-to-treat patients, most stayed on the combination — about 69% were still on it after roughly a year — and a similar proportion had major improvement in disease activity.
Importantly, more than half were able to get off steroids, and serious side effects were uncommon — only a handful of patients had a serious problem that made them stop.
Is it safe to combine two biologics?
This is probably the most important question.
On the safety question specifically, a large 2025 analysis of U.S. insurance data looked at patients on combination targeted therapy and found no significant increase in serious or opportunistic infections compared with standard single-drug therapy.
That’s reassuring.
But the authors were careful to say the numbers are still small and bigger studies are needed before we call it settled.
The fact that early data are reassuring does not mean that combining two biologics is risk-free.
These medications affect the immune system, and infection risk is something I take seriously when considering any combination of immune-targeting therapies.
What do the guidelines say about combining biologics?
This is the part I don’t want to gloss over.
The major rheumatology guidelines still recommend switching from one biologic to another — not combining them — when your current biologic isn’t cutting it.
When one biologic falls short, the standard move is to swap to a different mechanism.
For example, you might switch from a TNF inhibitor to an IL-17 inhibitor, or from an IL-17 inhibitor to a TNF inhibitor.
Real-world data support that switching mechanisms can often work better than simply cycling through similar drugs.
Combining two biologics is not a standard, first-line, or even second-line strategy.
It’s an option reserved for genuinely difficult cases — often people who also have a second inflammatory condition, such as inflammatory bowel disease, that may be driving the decision.
So, can you combine a TNF blocker with an IL-17 or IL-23 blocker?
Here’s my practical bottom line:
Combining a TNF blocker with an IL-17 or IL-23 blocker is possible in carefully selected patients with truly refractory disease or overlapping inflammatory conditions, but it is not standard treatment.
For most people, if one biologic isn’t working well enough, switching to a different mechanism remains the preferred approach.
The biggest concern is infection risk. Early data are reassuring, but the studies are small, and we need more research.
If your skin and joints are pulling in different directions, or standard switching has failed, this can be a thoughtful conversation with your rheumatologist.
If you’re stuck in that “one part of me is better, the other isn’t” limbo, don’t lose hope and don’t self-adjust your medicines.
Bring it to your next visit.
We have more tools — and more thoughtful ways to combine or switch them — than we’ve ever had before.
References
Dual Targeted Therapy in Patients With Psoriatic Arthritis and Spondyloarthritis: A Real-World Multicenter Experience From Spain. Valero-Martínez C, Urgelles JF, Sallés M, et al. Frontiers in Immunology. 2023;14:1283251. doi:10.3389/fimmu.2023.1283251.
Comparative Risk of Infection and Prevalence of Combination Targeted Therapy in Psoriatic Arthritis. Wu A, Zhang A, Guo Y, et al. JAMA Dermatology. 2025;161(11):1162-1166. doi:10.1001/jamadermatol.2025.2980.
Special Article: 2018 American College of Rheumatology/National Psoriasis Foundation Guideline for the Treatment of Psoriatic Arthritis. Singh JA, Guyatt G, Ogdie A, et al. Arthritis & Rheumatology (Hoboken, N.J.). 2019;71(1):5-32. doi:10.1002/art.40726.