Hydroxychloroquine’s been a big name in the fight against rheumatoid arthritis (RA) and lupus, but it’s definitely not the only player on the team. Maybe it’s causing you stomach issues, messing with your eyes, or just isn’t working anymore. You’re not alone—lots of people end up searching for other options that fit their life and symptoms better. The truth is, no single medication works for everyone, and finding something that actually helps feels like winning the lottery.

There’s good news, though: you have other choices. Whether you want something you can grab at the pharmacy or you need a doctor’s prescription for something more serious, there’s a range of meds out there—each with their own perks and downsides. In this article, I’ll walk you through eight alternatives to hydroxychloroquine, explain how they work, and point out the stuff you need to know before making any changes. Let’s get real about your options, one step at a time.

• NSAIDs (e.g., Ibuprofen, Naproxen)
• Methotrexate
• Leflunomide
• Sulfasalazine
• Corticosteroids
• Biologic DMARDs
• Azathioprine
• Mycophenolate Mofetil
• Conclusion & Comparison Table

NSAIDs (e.g., Ibuprofen, Naproxen)

When people think about quick fixes for joint pain and swelling, NSAIDs like ibuprofen and naproxen are usually at the top of the list. You probably have a bottle of one of these in your bathroom cabinet right now. They’re the classic go-tos for everything from twisted ankles to headaches, but they also play a role in chronic conditions like rheumatoid arthritis and lupus.

The science behind these drugs is pretty straightforward—they block enzymes called COX-1 and COX-2, which are involved in making prostaglandins. Those little troublemakers are what cause swelling, pain, and fever when your immune system flares up. By taking away some of these chemicals, NSAIDs toss a wet blanket on the fire.

But before you start grabbing pills left and right, it’s smart to weigh out the good and the bad. Here’s what you really need to know:

Pros

• Work fast—most folks start to feel relief within an hour or two.
• Available over the counter (OTC) at any pharmacy or grocery store.
• Affordable, especially for generic versions.
• Good for occasional flare-ups or when you just need a break from nagging pain.

Cons

• Don’t slow down or stop the actual disease—just masks symptoms.
• Long-term use can mess with your stomach—think ulcers or bleeding.
• May cause issues with your kidneys or raise blood pressure if you use them constantly.
• Not strong enough for major inflammation or aggressive symptoms.

Here’s something wild: about 1 in 5 adults with rheumatoid arthritis depend on NSAIDs for regular symptom control, even though only about 30% say they’re happy with that alone. That just shows how tricky it can be to balance relief with the possible risks.

It’s always a good move to talk to your doctor before leaning on NSAIDs for the long haul, especially if you’ve got heart, kidney, or stomach problems in your history. These drugs can make a huge difference on rough days, but they aren’t a long-term solution if your goal is actually controlling lupus or rheumatoid arthritis.

Methotrexate

If you’ve been poking around for alternatives to hydroxychloroquine, you’ve probably seen methotrexate listed as a top choice. It’s actually considered the gold standard for treating rheumatoid arthritis and is widely used in tough cases of lupus too. Methotrexate isn’t a painkiller—it works by turning down the immune system’s overreaction, so it gets to the root of what’s causing the inflammation.

Doctors usually start folks on methotrexate if NSAIDs or hydroxychloroquine just aren’t enough. It comes as a pill you take once a week, or sometimes as an injection if your gut can’t handle the pill version. Methotrexate helps slow down the joint damage and keeps you moving for years longer than you would otherwise. Real talk: many people who switch see a big difference in swelling and pain after just a month or two.

Pros

• Actually slows or stops the underlying disease, not just symptoms
• Taken weekly—easy to remember
• Proven track record: over 30 years of use, tons of studies backing it
• Can reduce the need for steroids and NSAIDs over time

Cons

• Can mess with your liver and blood cells—regular blood tests required
• Common side effects: nausea, mouth sores, fatigue
• No go during pregnancy (it’s not safe for unborn babies)
• May take 4–8 weeks before real results show up

Some interesting numbers: a 2023 study found that nearly 60% of RA patients on methotrexate saw at least a 50% improvement in joint pain and stiffness in the first three months. To help with side effects, doctors often suggest taking it with folic acid—which cuts down on that rough feeling some folks get after taking their weekly dose.

Before jumping into methotrexate, talk with your doctor about your health history—especially if you drink alcohol, have liver problems, or want to have kids someday. Staying on top of blood tests keeps you safe and makes it way more likely you’ll get the benefits without a bunch of drama.

Leflunomide

Leflunomide is another pill you might hear about if hydroxychloroquine just isn’t cutting it for rheumatoid arthritis (RA). It’s not as famous as methotrexate, but it’s a real option, especially if your body can’t handle the usual first-line drugs. Leflunomide works by slowing down your immune system—a big deal in RA, where your immune cells are basically running wild and attacking your own joints. This drug helps put the brakes on that chaos.

Most folks taking leflunomide notice a drop in swelling, pain, and morning stiffness after a few weeks, but it can take up to a few months to see the full benefit. Doctors usually start with a loading dose (a higher amount for the first few days) to get it working faster, then switch you to a lower daily dose.

Pros

• Helps slow or stop joint damage—not just treat symptoms
• Oral medication, so no injections needed
• Might work better than hydroxychloroquine if your disease is more aggressive
• Alternative for people who can’t take methotrexate

Cons

• Can cause liver problems—you’ll need regular blood tests
• Not safe in pregnancy or for people planning to have kids (it stays in your system for a long time)
• May cause hair thinning, diarrhea, or high blood pressure
• Immune suppression means higher risk of infections

Doctors pay close attention to your liver tests with leflunomide. If your liver numbers creep up, you might have to lower your dose or even stop the drug. It’s also not something you can just quit cold turkey if you’re planning a pregnancy—it can hang around in your body for up to two years! There’s a special treatment (using cholestyramine) to flush it out, but you’ll need to plan ahead.

Just to give you an idea, a real-world study found that around 70% of people on leflunomide saw improvement in their joint swelling and pain after 6 months. But, about 10-15% ended up switching due to side effects, so it’s all about weighing that balance with your rheumatologist. Here’s a snapshot:

If you’ve tried hydroxychloroquine and it’s just not doing the trick, leflunomide is a legitimate step up. Just remember—regular checkups and honest conversations with your doctor keep you safer and get you better results.

Sulfasalazine

Sulfasalazine is a real workhorse when it comes to treating rheumatoid arthritis and even mild cases of lupus. This drug has actually been in use since the 1950s, which means doctors have had decades to test its strengths and weaknesses. It’s not the flashiest option, but it can tame joint pain and stiffness for a lot of folks who can’t handle hydroxychloroquine or want a second-line treatment.

How does sulfasalazine work? It helps reduce inflammation by tinkering with your immune system. This isn’t a quick fix—it might take several weeks, sometimes up to three months, before you actually notice your joints moving easier or your morning stiffness isn’t ruining your whole day. The good news: most people tolerate sulfasalazine pretty well, and it’s usually taken as a pill, so you don’t have to mess with shots or infusions.

Pros

• No needles—oral tablets only.
• Works for both RA and mild to moderate lupus symptoms.
• Affordable compared to newer drugs and often covered by insurance.
• Can be safely combined with other RA drugs like methotrexate for better results.
• Doesn’t usually cause weight gain or severe fatigue.

Cons

• Some folks get stomach upset, nausea, or headaches—especially when starting.
• Can tint your pee or sweat orange (harmless, but weird if you’re not expecting it).
• Rare but serious side effects: allergic reactions, drop in blood cell counts, or liver issues—so regular blood tests are a must.
• Not recommended if you have a sulfa allergy.
• Takes a while to kick in, so you’ll need patience at first.

Just a small tip: If the nausea or stomach upset hits you hard, try splitting the dose to twice a day and always take it with food. Stay hydrated, and let your doctor know if you notice any unexplained bruising or yellowing of your skin.

Corticosteroids

Corticosteroids—like prednisone and methylprednisolone—are pretty much the go-to for fast relief when rheumatoid arthritis or lupus flares up and you need to get things under control quick. These drugs work by blocking inflammation fast, so you’re not stuck waiting weeks or months for some relief. People usually take them as pills, but for really bad swelling, doctors might inject them right into the joint. Sometimes a low daily dose gets the job done; other times, it’s just for a short burst to calm things down.

They’re popular because they start working within hours, not days. That’s a lifesaver if your joints are screaming or your lupus is attacking your organs. For some folks, they can be a bridge until other meds, like methotrexate or biologics, have a chance to kick in. But nobody likes living on steroids long-term, and there are good reasons why.

Pros

• Very fast symptom relief—sometimes within just a few hours
• Can be used in pill, liquid, or injection form for flexibility
• Helpful in severe or sudden flares when other meds are too slow
• Useful as a bridge while starting slower-acting drugs
• Well-studied and familiar option for doctors to manage RA and lupus

Cons

• High risk of side effects with long-term use (weight gain, osteoporosis, diabetes, high blood pressure, mood swings, and infections)
• Does not change the underlying course of the disease—just manages symptoms
• May cause withdrawal symptoms if stopped suddenly after long-term use
• Long-term use can make bones weak and raise blood sugar
• Can suppress immune system, making infections more common

Bottom line: steroids work fast, but they aren’t a good long-term fix for most people with RA or lupus. If you need them for weeks or months, ask your doctor about a bone density scan or extra blood work, just to keep things safe. And always talk with your doc before starting or stopping any steroid—it’s not the kind of med you want to mess around with on your own.

Biologic DMARDs

If you feel like standard drugs are just nibbling at the edges of your rheumatoid arthritis or lupus symptoms, Biologic DMARDs are the heavy-hitters in the world of autoimmune meds. DMARD stands for disease-modifying antirheumatic drugs, and biologics are the newest class in this category. They’re built from living proteins and specifically target immune system pathways that drive inflammation. These treatments are often used when regular DMARDs, like methotrexate, haven’t done enough.

Some names you’ll see: adalimumab (Humira), etanercept (Enbrel), infliximab (Remicade), and abatacept (Orencia). Each one goes after a different part of the immune system, which can make a real difference for people who haven’t found relief elsewhere.

Pros

• Can slow down or even stop joint damage, not just reduce symptoms
• Target specific immune processes, which often means better results for tough cases
• Can improve physical function and overall quality of life
• Options available by injection or IV infusion

Cons

• High cost—insurance often covers them, but out-of-pocket costs can be serious
• Increased risk of infection, including rare but serious ones like tuberculosis
• Need regular monitoring with blood tests
• Can require self-injection or trips to an infusion center

Here’s a quick look at how some common biologic DMARDs stack up for RA:

If you’re tired of just masking symptoms and want to try hitting the disease where it really starts, it’s worth asking your doctor about these options. Just be ready for more monitoring and some homework on insurance coverage. Biologics aren’t for everyone, but they’ve changed the game for plenty of people with serious symptoms.

Azathioprine

Azathioprine is a common backup when hydroxychloroquine just isn’t cutting it, especially for folks with stubborn lupus or RA. This med comes from the world of organ transplants (where it’s used to prevent rejection), but doctors realized it can chill out immune systems that are attacking themselves, too.

The main way azathioprine works is by slowing down immune cell production. That helps tamp down inflammation, which is right at the heart of both rheumatoid arthritis and lupus. You might hear doctors call it a "steroid-sparing agent"—that just means it lets you drop your steroid dose or maybe quit steroids altogether.

You’ll usually take azathioprine as a daily pill. Dosing can start low and climb up, depending on symptoms and blood test results. It takes some patience, though: the benefits usually show up after several weeks, not overnight.

Pros

• Helps with moderate to severe lupus or RA when other meds aren't enough
• Lets many folks reduce their steroid use (always a plus!)
• Often well-tolerated if you stick to regular checkups
• Generic versions mean it’s relatively affordable

Cons

• Requires regular blood tests—watching for low white cells and liver blips is a must
• Raises infection risk, so colds and bugs can hit harder
• Can take 2-3 months before you really notice benefits
• Not safe in pregnancy without special doctor oversight

Interestingly, a review in 2021 found azathioprine works about as well as mycophenolate for keeping lupus in remission, but side effects were a bit more common. Here’s a quick snapshot if you like numbers:

If you’re itching to switch, talk to your rheumatologist. They’ll help you weigh if azathioprine’s risks make sense with your health history and lifestyle. It’s all about finding what works for your body without causing more problems than it solves.

Mycophenolate Mofetil

Mycophenolate mofetil started out helping people after organ transplants, but it’s found a real use in fighting serious autoimmune problems like lupus (especially lupus nephritis). You might hear doctors call it "Cellcept." It gets used when classic meds—like hydroxychloroquine or NSAIDs—don’t get the job done, or when someone’s dealing with kidney issues tied to lupus.

This drug works by taming your immune system. It basically dials down the body’s attack on itself, which is a big win for keeping organs from getting wrecked. Mycophenolate is usually prescribed as a pill you swallow, and doctors typically start low and ramp up the dose depending on how your body reacts and how severe your symptoms are.

People sometimes see results fast— within a few months, kidney-related labs often improve, and doctors recommend regular blood tests to track if it’s working (and that you’re not dealing with side effects).

Pros

• Helps control tough cases of lupus when other medications quit working
• Can be safer for kidneys than some other immunosuppressants
• Usually leads to better kidney test results in lupus nephritis
• Comes in pill form, making it easier to take than an injection

Cons

• Makes you more likely to catch infections—your immune system can’t fight like it used to
• Not ideal if you’re pregnant or planning to be (it can cause birth defects)
• Possible side effects: stomach pain, diarrhea, or low blood cell counts
• Needs regular blood tests to watch out for liver, kidney, or blood problems

If you’re struggling with rheumatoid arthritis or lupus, especially if your kidneys are involved, this is definitely an option to talk about with your doctor. Just remember—monitoring is non-negotiable, and being upfront about any side effects is key.

Conclusion & Comparison Table

Switching from hydroxychloroquine isn’t always simple, but nobody should have to stick with a drug that causes problems or doesn’t clear up symptoms. There’s no one-size-fits-all answer for rheumatoid arthritis or lupus—some folks do best with older meds like NSAIDs, while others need bigger guns like biologics or immunosuppressants. Each option comes with trade-offs you’ll want to talk through with your doctor, especially since side effects and the way the drug works can be pretty different.

Let’s break it down and look at how these main choices stack up against hydroxychloroquine. This table makes it easier to see what you’re really getting—so if you’re planning to bring up alternatives at your next appointment, you’ll know what questions to ask.

If you’re considering changing from hydroxychloroquine, write down your symptoms, what’s improved or gotten worse, and any side effects. Bring your list to your appointment—it makes the discussion more productive. Lots of people end up tweaking their meds until they find something that actually works for their body. Don’t give up if the first switch isn’t the answer; sometimes it takes a couple of tries.

One last thing: never switch or stop meds on your own. Use this info as a guide to have a smarter conversation with your doctor, not as a replacement for medical advice. There’s always a way to get closer to feeling better—you just need the right info and support to get there.