Abatacept and Natalizumab: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 16, 2026 · Source data updated Jul 16, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Abatacept
Natalizumab
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Abatacept (Orencia) and natalizumab both calm down your immune system. Each one works in a different way, but when you take them together, your body may have a harder time fighting off germs. That means a higher chance of getting a serious infection, and doctors haven't found that combining them helps any more than using one alone.
Because of this, using these two together is generally not recommended. Please don't stop or change anything on your own. Your care team knows how to handle this safely, and they can choose the right plan for you and watch closely for any signs of infection.
Effect: Additive immunosuppression, increasing the risk of serious infection with no added therapeutic benefit.
- Direction: Both agents suppress immune function via distinct mechanisms (abatacept = T-cell costimulation blockade; natalizumab = alpha-4 integrin inhibition). Combined use compounds infection risk. Neither is a prodrug; no PK/enzyme mechanism involved.
- Evidence: Theoretical, extrapolated from controlled trials of abatacept plus TNF antagonists showing increased serious infection.
- Onset: Unspecified.
- Management: Concurrent biologic immunosuppressant therapy is not recommended. If transitioning between agents, monitor closely for signs and symptoms of infection.
What happens
An increased risk of infection
Interaction Deep Dive
In controlled clinical studies, combining abatacept with tumor necrosis factor (TNF) antagonists led to a higher likelihood of serious infection while offering no extra therapeutic benefit. Data are inadequate to assess the safety and effectiveness of abatacept given together with anakinra or with biologic agents used for rheumatoid arthritis or psoriatic arthritis. For this reason, using these agents at the same time is not advised. Patients switching from TNF antagonist therapy to abatacept should be watched for signs of infection1.
Why it happens (mechanism)
Unknown
How to manage this interaction
The main step here is avoiding the overlap. Combining abatacept with natalizumab or other immune-suppressing biologics is generally not recommended because of the added infection risk.
- Keep taking your medications exactly as prescribed, and don't stop either one on your own.
- Tell your prescriber or pharmacist that you are on (or were on) both, so your care team can decide on the safest single therapy for you.
- If you are switching from one to the other, your team may monitor you more closely for signs of infection (fever, chills, sore throat, cough, or a wound that won't heal).
- Report any of those symptoms promptly.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) Using abatacept together with etanercept produced no extra efficacy but raised the likelihood of serious infection when compared with etanercept by itself. In a 1-year randomized study (N=121) that was followed by an open-label long-term extension (LTE; n=80), rheumatoid arthritis patients who were already receiving etanercept 25 mg twice/week continued that etanercept and were randomized to receive either abatacept 2 mg/kg IV on days 1, 15, and 30, and thereafter every 4 weeks (n=85), or placebo (n=36). After finishing the double-blind phase, patients could enter the LTE phase, at which point the abatacept dose was raised to approximately 10 mg/kg. At 6 months, the 2 mg/kg abatacept group demonstrated no significant improvement versus the placebo group in modified American College of Rheumatology 20% (ACR20; 48.2% vs 30.6%) or ACR50 (25.9% vs 19.4%) response rates, though there was a significant difference in modified ACR70 rates (10.6% vs 0%). At 1 year, no significant differences in ACR20, 50, or 70 response rates were seen between the two groups. Serious adverse events occurred more often in the 2 mg/kg abatacept group (16.5%) at one year and in the 10 mg/kg abatacept group after 2 years of LTE (32.5%) than in the placebo group (2.8%). At 1 year, serious infections were reported in 3.5% of the 2 mg/kg abatacept group and 0% of the placebo group 2.
b) In controlled clinical trials involving adults with active rheumatoid arthritis who received abatacept together with a tumor necrosis factor (TNF) antagonist (n=204) versus TNF antagonist therapy on its own (n=134), the rate of infection (63% vs 43%, respectively) and of serious infection (4.4% vs 0.8%, respectively) was higher with the combined therapy; additionally, the combined therapy offered no added benefit 1.
Common questions
Can I take Abatacept and Natalizumab together?
Using abatacept and natalizumab together stacks two immune-suppressing drugs and raises your risk of serious infection without added benefit, so this combination is generally avoided. Talk with your prescriber or pharmacist about the safest single option and watch for signs of infection. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Abatacept and Natalizumab interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Abatacept and Natalizumab interaction managed?
The main step here is avoiding the overlap. Combining abatacept with natalizumab or other immune-suppressing biologics is generally not recommended because of the added infection risk. Keep taking your medications exactly as prescribed, and don't stop either one on your own. Tell your prescriber or pharmacist that you are on (or were on) both, so your care team can decide on the safest single ther… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Abatacept or Natalizumab need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (2)
- Product Information: ORENCIA(R) intravenous, subcutaneous injection, abatacept intravenous, subcutaneous injection. Bristol-Myers Squibb Company (per FDA), Princeton, NJ, 2020. DailyMed
- Weinblatt M, Schiff M, Goldman A, et al: Selective costimulation modulation using abatacept in patients with active rheumatoid arthritis while receiving etanercept: a randomised clinical trial. Ann Rheum Dis 2007; 66(2):228-234. PubMed
Keep reading about Abatacept
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