Compare Arava (Leflunomide) with Alternatives for Rheumatoid Arthritis

When you’re managing rheumatoid arthritis, finding the right medication isn’t just about reducing pain-it’s about keeping your life moving. Arava (leflunomide) has been a go-to option for years, but it’s not the only one. And for many people, it’s not even the best fit. If you’ve been on Arava and felt like it’s not working, or if you’re just starting treatment and want to know what else is out there, you’re not alone. Let’s break down how Arava stacks up against other common treatments, what the real trade-offs are, and who might do better on something else.

What Arava (Leflunomide) Actually Does

Arava is a disease-modifying antirheumatic drug, or DMARD. That means it doesn’t just mask your symptoms-it slows down the immune system’s attack on your joints. Leflunomide works by blocking an enzyme called dihydroorotate dehydrogenase, which stops immune cells from multiplying too fast. It’s taken as a daily tablet, usually 20 mg. Most people start seeing results after 4 to 6 weeks, but full effects can take up to 6 months.

It’s not a quick fix. Unlike steroids or NSAIDs, Arava doesn’t give you instant relief. But if it works, it can stop joint damage before it becomes permanent. That’s why doctors often prescribe it early, especially for people with moderate to severe rheumatoid arthritis.

Why People Look for Arava Alternatives

Not everyone tolerates Arava. Side effects are common and sometimes serious. Diarrhea affects about 20% of users. Liver enzyme changes happen in up to 15%. Some people lose hair. Others feel constantly tired or get rashes. In rare cases, it can cause severe liver damage or lower white blood cell counts, making infections more likely.

Then there’s the washout process. If you need to stop Arava-say, because of side effects or because you’re planning a pregnancy-you have to take cholestyramine for days to flush it out of your system. That’s not something you can just skip. And if you’re on other meds, like blood thinners or statins, interactions can get messy.

That’s why many patients and doctors look elsewhere.

Methotrexate: The Gold Standard

Methotrexate is still the first-line treatment for rheumatoid arthritis in most guidelines. It’s been around since the 1980s, and it’s cheap-often under $10 a month. It’s taken once a week, either as a pill or injection. Most people start at 7.5 to 15 mg per week and adjust based on response.

Compared to Arava, methotrexate works faster. You might feel better in 3 to 6 weeks. It also has more long-term data: studies show it reduces joint damage and improves function over 10+ years. It’s also the most common drug used in combination therapies.

But it’s not perfect. Nausea is common, especially at first. Liver toxicity is a risk, so regular blood tests are needed. Folic acid is usually prescribed alongside it to reduce side effects. And if you’re planning a pregnancy, you need to stop methotrexate at least 3 months before trying to conceive-longer than Arava’s washout.

So who wins? For most people, methotrexate is still the best starting point. But if you can’t tolerate it, Arava is often the next step.

Hydroxychloroquine: The Gentle Option

Hydroxychloroquine (Plaquenil) is an antimalarial drug that’s also used for mild rheumatoid arthritis. It’s often paired with methotrexate or used alone in early, low-activity cases. It’s known for being gentle on the body. Side effects are usually mild: stomach upset, dizziness, or rare eye changes (which is why annual eye exams are recommended).

It doesn’t work as strongly as Arava or methotrexate. If you have moderate to severe disease, it’s unlikely to be enough on its own. But for someone with early-stage RA or who needs a low-risk option-maybe an older adult or someone with liver concerns-it’s a smart choice.

And unlike Arava, there’s no washout needed. You can stop it anytime without special steps.

Sulfasalazine: The Old-School Choice

Sulfasalazine is another classic DMARD. It’s a combo of a sulfa drug and a salicylate. It’s taken twice a day, and like Arava, it takes weeks to kick in. It’s often used in people who can’t take methotrexate or when arthritis affects the gut too-like in cases linked with inflammatory bowel disease.

Side effects include nausea, headaches, and a rare but serious drop in blood cell counts. People with sulfa allergies should avoid it. It’s not as commonly prescribed today, but it’s still in the toolbox, especially in places where newer drugs are too expensive.

Compared to Arava, sulfasalazine has less data on preventing joint damage. But it’s cheaper and has been used for decades with solid safety records.

Biologics: When DMARDs Aren’t Enough

If Arava, methotrexate, and other traditional DMARDs don’t control your symptoms after 3 to 6 months, your doctor might suggest a biologic. These are targeted therapies that block specific parts of the immune system. Examples include adalimumab (Humira), etanercept (Enbrel), and abatacept (Orencia).

Biologics work faster than Arava-often in 2 to 4 weeks. They’re given by injection or IV, and they’re much more expensive. But they’re also more effective for severe cases. Studies show they reduce joint damage better than traditional DMARDs alone.

The catch? They increase your risk of serious infections like tuberculosis or fungal infections. You need screening before starting. They’re also not usually prescribed alone-they’re often added to methotrexate.

So if you’re struggling with Arava and still have active joint swelling, a biologic might be the real game-changer-not just an alternative.

JAK Inhibitors: The New Kids on the Block

Drugs like tofacitinib (Xeljanz), baricitinib (Olumiant), and upadacitinib (Rinvoq) are oral JAK inhibitors. They’re newer than Arava and work inside cells to block inflammation signals. They’re taken daily as pills, just like Arava.

They’re faster than Arava-often showing results in 2 to 4 weeks. And they’re effective even if you didn’t respond to methotrexate or other DMARDs. In trials, JAK inhibitors often outperformed Arava in reducing joint pain and swelling.

But they come with warnings. The FDA has flagged increased risks of heart problems, blood clots, and certain cancers, especially in people over 50 with risk factors like smoking or high blood pressure. Because of this, they’re usually reserved for patients who haven’t responded to other treatments.

So while JAK inhibitors are powerful, they’re not the first choice for everyone. But if Arava didn’t work for you and you’re looking for an oral option (not an injection), they’re worth discussing.

Comparing the Options

Who Should Avoid Arava?

Arava isn’t safe for everyone. You should not take it if:

• You’re pregnant or planning to become pregnant (it can cause severe birth defects)
• You have active liver disease or abnormal liver tests
• You have a weakened immune system or frequent infections
• You’re allergic to leflunomide or similar drugs
• You’re taking medications that interact badly with it, like certain statins or warfarin

If any of these apply to you, your doctor will likely skip Arava entirely and go straight to another option.

What If Arava Didn’t Work for You?

It’s not uncommon. Studies show that about 30-40% of people don’t respond well to Arava after 6 months. If you’re still having joint pain, swelling, or morning stiffness, it’s time to reassess.

Don’t just keep taking it hoping it’ll kick in. Talk to your rheumatologist about switching. The next step could be:

1. Moving to methotrexate if you haven’t tried it
2. Adding a biologic or JAK inhibitor
3. Trying hydroxychloroquine or sulfasalazine as a milder alternative

And if you’re worried about side effects, ask about liver monitoring. Blood tests every 6-8 weeks are standard on Arava. If your liver enzymes keep climbing, it’s a sign to switch.

Final Thoughts: It’s Not One-Size-Fits-All

There’s no single best drug for rheumatoid arthritis. What works for your neighbor might not work for you. Arava is effective for some, but it’s not the first choice for most. Methotrexate still leads the pack. Biologics and JAK inhibitors offer powerful options when older drugs fail. And for milder cases, hydroxychloroquine might be all you need.

The key is to be patient, stay in touch with your doctor, and don’t settle if you’re still in pain. Your treatment plan should evolve as your body changes. And if Arava isn’t working-or isn’t tolerable-you have more options than you think.

Next Steps

If you’re on Arava and unsure whether it’s right for you, start with these steps:

1. Track your symptoms: note joint pain, swelling, and morning stiffness daily.
2. Ask for a blood test: check liver enzymes and complete blood count.
3. Review your goals: are you aiming to reduce pain, prevent damage, or both?
4. Schedule a talk with your rheumatologist: bring your symptom log and ask, "What’s the next step if this isn’t working?"

There’s no shame in switching treatments. Rheumatoid arthritis is complex, and finding the right fit takes time. You’re not failing-you’re adjusting. And with the right plan, you can keep living your life, not just managing symptoms.