Rheumatoid arthritis alone does not make you immunocompromised, but the medications used to treat it often do. The distinction matters because it changes your infection risk, your vaccination schedule, and how doctors manage your care. Most people with RA who are considered immunocompromised earn that classification because of their treatment, not their diagnosis.
Why RA Itself Is Not Immunodeficiency
Rheumatoid arthritis is an autoimmune condition, meaning your immune system is overactive rather than weak. It mistakenly attacks your own joint tissue, causing chronic inflammation, pain, and eventual joint damage. This is the opposite of immunodeficiency, where the immune system fails to mount an adequate defense against infections.
That said, the overactive immune response in RA does come with a measurable cost. People with RA have roughly 1.5 to 1.7 times the rate of serious infections compared to people with non-inflammatory conditions, even before accounting for medications. Part of this likely reflects the immune system being misdirected: resources spent attacking joints are resources not optimally deployed against bacteria and viruses. But once researchers adjust for steroid use, much of that excess risk shrinks, suggesting medication is the bigger driver.
How RA Medications Suppress Your Immune System
The goal of RA treatment is to dial down the immune attack on your joints. The trade-off is that the same drugs also reduce your body’s ability to fight infections. How much depends on which medication you take and at what dose.
Conventional Oral Medications
Methotrexate, the most commonly prescribed RA drug, works by dampening immune cell activation and reducing the production of several inflammatory signaling molecules. It broadly lowers the immune system’s intensity rather than targeting a single pathway. Leflunomide takes a different approach, starving rapidly dividing immune cells of a building block they need to multiply. Hydroxychloroquine is the mildest option and interferes with how immune cells process and respond to threats, though its effect on infection risk is relatively small compared to other drugs in this category.
Biologic Therapies
Biologics are engineered proteins that block specific parts of the immune system. TNF blockers (drugs like adalimumab, etanercept, and infliximab) neutralize a key inflammatory molecule called TNF-alpha. Other biologics deplete certain immune cells entirely: rituximab, for example, wipes out a type of white blood cell called B cells, reducing autoantibody production but also weakening your defense against some infections. Additional biologics block other inflammatory signals like IL-6 or prevent immune cells from fully activating.
These targeted therapies carry real infection consequences. A 10-year follow-up study of RA patients on biologic therapy found cases of invasive fungal infections (especially oral and systemic candidiasis), tuberculosis, hepatitis B reactivation, herpes zoster flares, and unusual bacterial infections like legionella and salmonella. Several of these required hospitalization.
JAK Inhibitors
A newer class of oral medications (tofacitinib, baricitinib, upadacitinib) works by blocking enzymes inside immune cells that relay inflammatory signals. These drugs suppress the expression of immune genes central to autoimmunity, but they also broadly reduce immune surveillance in a way that increases susceptibility to infections, including shingles.
The Official CDC Classification
The CDC considers you moderately to severely immunocompromised if you are actively taking any of the following: high-dose corticosteroids (20 mg or more of prednisone daily for two or more weeks), TNF blockers, B-cell-depleting agents like rituximab, or other biologic and immunosuppressive drugs. This classification was developed during the COVID-19 pandemic to guide vaccination schedules, but it reflects a broader medical reality about how these drugs affect immune function.
If you take hydroxychloroquine alone or a low dose of prednisone for a short period, you likely would not meet this threshold. If you take methotrexate combined with a biologic, you almost certainly would. The classification exists on a spectrum, and your specific drug regimen determines where you fall.
What This Means for Vaccines
Being classified as immunocompromised changes your recommended vaccination schedule in meaningful ways. The American College of Rheumatology’s 2022 guidelines highlight several key differences for people on immunosuppressive RA therapy.
- Pneumococcal vaccines are recommended for immunosuppressed adults under 65, a group that would not otherwise need them.
- Shingles vaccination (the recombinant version, not the older live vaccine) is recommended starting at age 18 for immunocompromised individuals, compared to age 50 for the general population.
- COVID-19 vaccines may follow a different dosing schedule with additional doses recommended for people on immunosuppressive medications.
- Live vaccines (such as the older shingles vaccine or the live nasal flu spray) are generally avoided while you are on immunosuppressive therapy, since a weakened immune system may not safely handle even an attenuated virus.
If you take rituximab or another B-cell-depleting therapy, timing matters. Vaccines given too close to an infusion may not generate an adequate immune response because the B cells needed to build antibodies have been depleted. Your rheumatologist can help coordinate vaccine timing around your treatment schedule.
Practical Infection Risk by Treatment Type
Not all RA medications carry the same level of immune suppression, and understanding the gradient helps you put your own risk in context. Hydroxychloroquine and sulfasalazine sit at the lower end, with modest effects on immune function. Methotrexate occupies the middle ground. Biologics and JAK inhibitors, especially when combined with steroids or methotrexate, carry the highest infection risk.
Corticosteroids deserve special attention because they are often used alongside other RA drugs during flares. Even short courses can temporarily increase infection susceptibility, and longer courses at higher doses are one of the strongest predictors of serious infection in RA. The research on RA infection rates found that adjusting for glucocorticoid use significantly reduced the apparent excess risk, meaning steroids account for a large share of the problem.
The infections that RA patients on immunosuppressive therapy are most vulnerable to include respiratory infections, urinary tract infections, skin infections, shingles reactivation, and, more rarely, opportunistic infections like tuberculosis or systemic fungal infections. Your doctor will likely screen you for latent tuberculosis before starting a biologic, and you should be aware that even common infections can progress more quickly or become more severe when your immune system is suppressed.
If You Are Not on Medication
People with RA who are not taking immunosuppressive drugs are not considered immunocompromised by any standard medical definition. Your immune system is dysregulated in the sense that it attacks your joints, but it is not weakened in a way that significantly impairs your defense against infections. The autoimmune process itself may slightly elevate infection risk, but the effect is small compared to what medications introduce. If your RA is managed with NSAIDs, physical therapy, or hydroxychloroquine alone, your immune function is largely intact for practical purposes.