Author: Diana Girnita, MD, PhD, FACR
Living with rheumatoid arthritis (RA) means dealing with joint pain, stiffness, and fatigue — often every single day. But 2026 is the year that brings real progress. New drugs are entering the pipeline, the treatment guidelines have been updated, and scientists are getting closer to a future where we as doctors can predict — before you even start — which medicine will work best for you.
A quick note: RA is an autoimmune disease. That means your immune system, which is supposed to protect you, mistakenly attacks your own joints instead. The goal of all RA treatment is to calm down that mistaken attack — safely and effectively.
The Treatment Guidelines Were Just Updated — Here Is What Changed
One of the most respected rheumatology organizations in the world — EULAR (the European version of the American College of Rheumatology)- released updated guidelines in early 2026. They shortened their recommendations from 12 to 9, meaning fewer rules but sharper and clearer.
Here are the changes that matter most to you as a patient.
Methotrexate is still the starting point
If you have been recently diagnosed with RA, your doctor will almost certainly still start with methotrexate (MTX). This has not changed. Methotrexate, usually combined with a short course of low-dose steroids, remains the recommended first treatment. The steroids help control inflammation quickly while the methotrexate kicks in over several weeks. This is what we also have been recommending here at Rheumatologist OnCall, one of the leading telehealth rheumatology companies in the United States.
The new guidelines also set a clear performance target: you should be at least 50% better within 3 months, and at your treatment goal by 6 months. If that is not happening, your treatment plan needs to change.
Biologic injections are now officially preferred over JAK inhibitor pills
This is the most important change for patients currently on or considering advanced therapy. When methotrexate alone is not enough, the new guidelines say: add a biologic first. Biologics are injectable or infused medications that target specific parts of the immune system — like TNF blockers (adalimumab, etanercept) or IL-6 blockers (tocilizumab).
JAK inhibitors — oral pills like tofacitinib (Xeljanz), baricitinib (Olumiant), and upadacitinib (Rinvoq) — are still an option, but should now only be considered after a careful review of your individual risk factors, particularly for blood clots, shingles, and in some cases certain cancers.
| What This Means for You If your doctor is talking about starting a JAK inhibitor for the first time, it is completely reasonable to ask: “Have you reviewed my heart health, clot history, and cancer risk before choosing this?” The guidelines now make that conversation mandatory. |
Good news if you are in remission: you may be able to reduce your medication
If your RA has been well-controlled for a sustained period, the 2026 guidelines support gradually reducing (tapering) your medication dose. This does not mean stopping everything — complete discontinuation is still not recommended because relapse rates are high. But if you are doing well, ask your rheumatologist whether a lower dose might be appropriate for you. This is our approach at Rheumatologist OnCall, since we believe strongly that fewer medications and lower doses will reduce your risk of side effects.
Preventing RA before it starts
For the first time, the EULAR systematic review included studies on preventing RA in people who test positive for autoantibodies (like anti-CCP and rheumatoid factor in blood tests) but have not yet developed full-blown disease. This is an exciting new direction — the idea of treating RA before it causes damage — and it will likely significantly shape future guidelines.
New Drugs Are Coming — And They Work Differently
The RA treatment pipeline in 2026 is more active than it has been in years.
Several new drugs have advanced through clinical trials, and some are targeting the immune system in completely new ways. Here is a plain-language breakdown of the most important ones.
A smarter, faster version of anti-TNF: Ozoralizumab (nanobody)
TNF blockers like adalimumab (Humira) have been the backbone of biologic RA treatment for over 30 years. They work by blocking TNF — a key inflammatory signal that drives joint damage. But a new drug called ozoralizumab does the same thing in a completely different way, and it may have real advantages.
Ozoralizumab is what is called a “nanobody” — a tiny antibody fragment that is about four times smaller than a conventional drug like adalimumab.
Here is why that matters:
- It reaches inflamed joint tissue much faster—within hours rather than days —so some patients in clinical trials noticed improvement within 2 to 3 days of the first injection.
- It causes far fewer injection site reactions — about 2% of patients versus 10 to 20% with conventional anti-TNF drugs.
- It is given just once a month, instead of every two weeks.
- It produces very few “anti-drug antibodies” — the immune response that causes many patients to lose their response to adalimumab over time.
- It may even work in patients whose previous anti-TNF therapy has become ineffective.
| Currently Available in Japan. Ozoralizumab was approved in Japan only in 2026. It is not yet available in the US or Europe. But it represents where anti-TNF therapy is heading. |
A completely new idea: turning on the immune system’s own “off switch.”
Every drug currently used for RA works by suppressing the immune system in some way. A drug called peresolimab does something no RA drug has done before: instead of suppressing the immune system broadly, it restores the immune system’s own natural brake.
Your immune system has a built-in “off switch” on immune cells called the PD-1 receptor. In healthy people, this off switch is activated when immune cells have done their job, telling them to stand down.
In RA, this off switch stops working properly in the joints, and immune cells keep attacking even when they should stop.
Peresolimab is a drug that directly activates this PD-1 off switch — essentially reminding your immune cells to stand down. Because it targets only actively misbehaving cells (those with the most PD-1 on their surface), it is much more precise than existing treatments.
What did the clinical trial show?
A Phase 2 trial published in the New England Journal of Medicine in 2023 tested peresolimab in 98 RA patients who had not responded well to existing treatments. The results were encouraging: meaningful improvement in joint swelling and tenderness compared to placebo. But the most striking finding was the safety profile — adverse events were nearly identical to placebo. No serious infections, no toxicities.
| Still in Development. Peresolimab is not yet approved anywhere. Larger trials are needed — and the question of long-term cancer risk needs careful study. But if the results hold up, this could become one of the safest RA treatments ever developed. |
New JAK inhibitors: ivarmacitinib and peficitinib
Two newer JAK inhibitors have significant Phase 3 trial data:
Ivarmacitinib is a highly selective JAK1 inhibitor — meaning it targets the specific JAK enzyme most relevant to RA inflammation, while leaving others largely alone. In a trial of 566 patients, 70-75% achieved meaningful improvement (ACR20), compared with 40% on placebo. It also reduced visible bone erosion on MRI. Not yet widely approved.
Peficitinib is a broader JAK inhibitor approved in Japan and South Korea. It showed strong efficacy in large trials. The shingles risk is elevated — consistent with the rest of this drug class — and it remains limited to Asian markets for now.
JAK Inhibitor Safety — What You Need to Know Right Now
JAK inhibitors are effective medications, but questions about their safety have led to label warnings in recent years. The 2025 EULAR safety review brings the most up-to-date picture.
Higher shingles risk — and what to do about it
The clearest finding is that JAK inhibitors increase the risk of shingles (herpes zoster) compared to biologic injections. Shingles is a painful rash caused by the reactivation of the chickenpox virus, which most adults carry dormant. Here at Rheumatologist OnCall, we always discuss with our patients the benefits and risks of getting the Shingrix vaccine, especially with those about to start a JAK inhibitor. Preventing shingles is always better than treating it.
Blood clot risk — mainly pulmonary embolism
The evidence confirms that JAK inhibitors carry a higher risk of venous blood clots — particularly pulmonary embolism (a clot in the lungs) — compared to biologic therapies. If you have a history of blood clots or significant risk factors for them (obesity, limited mobility, prior clot), this is an important factor in your treatment decision.
Heart attack and stroke risk — the picture is more reassuring
Despite earlier concerns, the 2025 EULAR review found no consistent evidence that JAK inhibitors cause more heart attacks or strokes than biologic injections overall. Caution remains appropriate for patients with existing heart disease, but for many patients, the cardiovascular risk is not the primary concern it was once thought to be.
| The Bottom Line on JAK Inhibitors. JAK inhibitors remain effective treatments for many RA patients. We use this type of medication quite often in our patients; however, the key is individualized risk assessment — your doctor should review your heart history, clot history, and cancer history before prescribing one. |
Precision Medicine — Getting the Right Drug the First Time
Right now, choosing an RA biologic is largely trial-and-error.
As rheumatologists, we pick the most likely candidate based on your history and risk factors, you try it for 3 to 6 months, and if it does not work, you try another.
For patients, this means months of ongoing pain and joint damage while waiting to find out if a drug works.
Precision medicine aims to change this by identifying, before treatment starts, which drug is most likely to work for your specific biology. The most advanced approach uses a tissue sample from the inflamed joint itself.
What is a synovial biopsy?
The synovium is the thin tissue that lines your joints. In RA, this tissue becomes inflamed and drives the damage to cartilage and bone. A synovial biopsy is a simple procedure — using ultrasound guidance, a doctor takes a tiny tissue sample from an affected joint (usually the knee or wrist) under local anesthesia. It takes about 20 to 30 minutes and is generally well-tolerated.
What the biopsy reveals: three types of RA
When researchers analyze synovial tissue at the molecular level, they find that RA is actually not one disease — it has three distinct subtypes:
- Lympho-Myeloid: The most active and aggressive type. B cells, T cells, and macrophages are all highly active. These patients tend to need biologic therapy and respond well to rituximab or IL-6 blockers.
- Diffuse-Myeloid: Moderate inflammation, driven mainly by macrophages. Often responds to IL-6 blockers and sometimes to conventional DMARDs.
- Pauci-Immune (Fibroid): Paradoxically, the fewest immune cells — but these patients often respond poorly to all current biologic therapies. This subtype is now a major focus for developing entirely new treatment approaches.
How close are we to using this in the clinic?
In 2025, researchers published results from an artificial intelligence analysis of synovial tissue samples from the STRAP clinical trial. Using machine learning on the full genetic data from these biopsies, they built models that could predict whether a patient would respond to etanercept, tocilizumab, or rituximab with impressive accuracy — and then converted those models into a practical test that could be run in hospital pathology laboratories.
The honest answer is: this is not in routine clinical practice yet.
The models need to be tested in a future trial where the biopsy results actually guide treatment decisions in real time. But we are genuinely closer than ever, and some academic rheumatology centers are already incorporating biopsy analysis into research protocols.
| Why This Matters? If precision medicine succeeds in RA, it could mean that, instead of trying drug after drug over months or years, doctors could tell you from the start which treatment is most likely to work for you specifically — saving time, money, and joint damage. |
Ready to Work with a Rheumatologist Who Keeps Up With the Science?
At Rheumatologist OnCall, we do not wait for treatments to become yesterday’s news before learning about them. Dr. Diana Girnita and our team actively follow the latest research. Whether you are newly diagnosed, frustrated that your current treatment has stopped working, or simply want a second opinion from a rheumatologist who reads the same journals that produce the breakthroughs described in this article — we are here.
Board-certified, evidence-based, and available via telehealth across many US states, without the months-long wait that comes with traditional specialty care. Your joints cannot afford to wait for medicine to catch up. At Rheumatologist OnCall, it already has.
Book your telehealth visit at rheumatologistoncall.com
Frequently Asked Questions
Q: What is the best biologic for rheumatoid arthritis in 2026?
There is no single “best” biologic — the right choice depends entirely on you: your other health conditions, disease severity, lifestyle, treatment history, and preferences. TNF blockers (adalimumab, etanercept, certolizumab), IL-6 blockers (tocilizumab, sarilumab), abatacept, and rituximab are all options. Your rheumatologist should walk you through which makes most sense for your specific situation. Precision medicine research is working toward making this choice much more personalized in the future.
Q: Are JAK inhibitor pills safe for RA?
JAK inhibitors are effective and widely used, but carry specific risks — particularly higher rates of shingles and blood clots compared to biologic injections. The 2025 EULAR guidelines now recommend biologics as the preferred first advanced therapy, with JAK inhibitors as an option after careful individual risk assessment. If you are already on a JAK inhibitor and it is working, discuss your individual risk picture with your rheumatologist. And if you are on one, ask about the Shingrix (shingles) vaccine.
Q: Can rheumatoid arthritis go into remission?
Yes — remission is a realistic and achievable goal for many RA patients with modern treatment. The 2026 guidelines set remission (or at minimum low disease activity) as the treatment target. Starting treatment early and following a treat-to-target approach — where your doctor adjusts your treatment until you reach your goal — gives you the best chance of remission. If you are currently not at your goal, talk to your rheumatologist about whether your treatment plan needs to change.
Q: Can I stop my RA medication if I feel better?
This is one of the most common questions in rheumatology. The short answer is: do not stop on your own. The 2026 guidelines support gradually reducing medication under close medical supervision if you are in sustained remission — but completely stopping treatment is not recommended because RA comes back in the majority of patients. If you are feeling well and wondering about reducing your medication, have that conversation with your rheumatologist. Never stop or reduce without guidance.
Q: What is the new nanobody drug for RA and when will it be available?
The nanobody drug is called ozoralizumab. It blocks TNF (the same target as adalimumab/Humira) but is four times smaller, works faster, causes fewer injection site reactions, is given once monthly, and may work even after conventional anti-TNF drugs have stopped being effective. It was approved in Japan in 2022 but is not yet approved in the US or Europe. There is no confirmed timeline for Western markets yet, but the science behind it is compelling, and it represents the future of anti-TNF therapy.
Q: What is the PD-1 agonist drug for RA and is it available?
Peresolimab is a PD-1 agonist — a drug that restores the immune system’s natural off-switch rather than suppressing immunity broadly. A Phase 2 trial published in the New England Journal of Medicine showed encouraging results with a remarkably clean safety profile. It is not yet approved anywhere. Larger Phase 3 trials are needed before it could become available. The main long-term question being studied is whether PD-1 stimulation could reduce the immune system’s ability to fight cancer — a question only larger, longer trials can answer.
Q: Should I get a shingles vaccine if I have RA?
Yes — if you are on a JAK inhibitor, the Shingrix vaccine is now strongly recommended by rheumatology guidelines. Shingrix is a non-live, recombinant vaccine (meaning it does not use a live virus) and is considered safe in immunocompromised patients. Even if you are not on a JAK inhibitor, patients with RA on biologic or conventional immunosuppressive therapy are at elevated shingles risk and vaccination is generally recommended. Talk to your rheumatologist about whether you have been vaccinated.
Q: What does it mean that RA treatment is becoming “personalized” or “precision medicine”?
Right now, choosing an RA biologic is largely trial and error — try one, wait 3 to 6 months, see if it works, try another if it does not. Precision medicine aims to predict from the beginning which drug will work for your specific biology. The most advanced approach uses a small tissue sample from your joint (a synovial biopsy) combined with advanced genetic analysis and AI to match you to the right drug before you start it. This is not yet available in routine clinical practice but is getting closer, and could transform RA treatment within the next few years.
Q: Can I see a rheumatologist via telehealth for my RA?
Yes — telehealth rheumatology is a practical and effective option for many RA patients, particularly for ongoing monitoring, medication management, lab review, and prescription renewals. Rheumatologist OnCall provides board-certified rheumatology care via telehealth across 20+ states, without the long wait times typical of in-person specialty care. Initial diagnosis and joint injection procedures still require in-person visits — but a significant portion of RA management can be done effectively and conveniently via telehealth.
Q: My RA drug stopped working. What are my options?
This is called secondary failure and it is very common — especially with TNF blockers over time, partly due to the development of anti-drug antibodies. Your options include switching to a biologic in a different class (for example, from a TNF blocker to an IL-6 blocker or abatacept), adding a different medication, or — if appropriate for you — trying a JAK inhibitor. The 2025 EULAR guidelines also support switching between biologics within the same class. In the future, synovial biopsy-based precision medicine may help guide these decisions. Talk to your rheumatologist about a formal reassessment if your current treatment is not working.
Selected References
- Smolen JS, et al. EULAR Recommendations for the Management of Rheumatoid Arthritis: 2025 Update. Annals of the Rheumatic Diseases. 2026.
- Konzett V, et al. Efficacy of Synthetic and Biological DMARDs: Systematic Literature Review for the 2025 EULAR Update. Annals of the Rheumatic Diseases. 2026.
- Laskou F, et al. Safety of Synthetic and Biological DMARDs: Systematic Literature Review for the 2025 EULAR Update. Annals of the Rheumatic Diseases. 2026.
- Tanaka Y. Ozoralizumab: First Nanobody Therapeutic for Rheumatoid Arthritis. Expert Opinion on Biological Therapy. 2023.
- Tuttle J, et al. A Phase 2 Trial of Peresolimab for Adults with Rheumatoid Arthritis. New England Journal of Medicine. 2023.
- Humby F, et al. Rituximab Versus Tocilizumab in Anti-TNF Inadequate Responders (R4RA). Lancet. 2021.
- Rivellese F, et al. Stratification of Biological Therapies by Pathobiology in Biologic-Naive RA (STRAP). Lancet Rheumatology. 2023.
- Lewis MJ, et al. Deep Molecular Profiling of Synovial Biopsies in the STRAP Trial. Nature Communications. 2025.
- Liu J, et al. Ivarmacitinib in Moderate-to-Severe RA: Phase III Results. Annals of the Rheumatic Diseases. 2025.
- Cappelli LC. Immune Checkpoint Inhibitors and Rheumatoid Arthritis: All Roads Lead to PD-1? Seminars in Arthritis and Rheumatism. 2025.
