Apr, 20 2025
If Hydroxychloroquine isn’t working out for you, you’re not alone. Between risk of eye problems, trouble with shortages, and mixed results for different diseases, tons of patients and doctors are looking at other options. It's not just a matter of swapping one pill for another—switching meds can mean different side effects, price tags, and even the way the drug is taken (yeah, some are shots, not tablets).
This guide unpacks 10 viable alternatives out there now, ranging from classic pills like Methotrexate to newer immune-targeting treatments like Xeljanz (Tofacitinib). Each option has its own pros, such as easier dosing or faster symptom relief, but also drawbacks, like weird side effects or the need for extra blood tests. You’ll find practical details that actually matter when you’re managing a tough condition like rheumatoid arthritis or lupus—and get a side-by-side comparison to make sense of it all when talking to your specialist.
- Xeljanz (Tofacitinib)
- Methotrexate
- Leflunomide
- Sulfasalazine
- Azathioprine
- Mycophenolate Mofetil
- Cyclophosphamide
- Rituximab
- Belimumab
- Abatacept
- Conclusion & Summary Table
Xeljanz (Tofacitinib)
Xeljanz (Tofacitinib) steps in as a big player for folks who either can’t take Hydroxychloroquine alternatives or haven’t gotten the relief they need. Xeljanz is a type of JAK inhibitor, which means it blocks certain signals in your immune system linked to inflammation. It’s mainly used for rheumatoid arthritis (RA), psoriatic arthritis, and ulcerative colitis—all conditions where your immune system is basically in overdrive.
One of the best things about Xeljanz is how fast it works. Unlike some RA drugs that take months to kick in, Xeljanz can start easing symptoms in a few weeks. Plus, it comes as a pill—not an injection—making it much more manageable than meds you have to get at a clinic.
Pros
- Kickstarts relief fast, often within 2-4 weeks (way quicker than most alternatives to Hydroxychloroquine).
- Simple oral tablets, so no needles or infusion appointments.
- Works even if you haven’t had luck with older drugs like Methotrexate.
Cons
- Way pricier than classic RA meds—the monthly cost can be a shock if you don’t have good insurance.
- Higher risk of serious infections because it tamps down parts of your immune system. This includes TB, shingles, and unusual lung infections. The FDA even flagged a warning for increased risk of serious heart-related problems and blood clots in some people.
- Requires ongoing blood tests—liver, blood count, and cholesterol—to catch side effects early.
If you want real numbers, Xeljanz has shown in clinical trials to reduce swollen joint count by over 50% in some patients within 3 months. But, up to 4% of users may develop serious infections each year, so doctors monitor closely.
| How It's Taken | Onset Time | Major Risks |
|---|---|---|
| Oral tablets, daily | 2-4 weeks | Infection, heart, clots |
Before starting Xeljanz, you’ll usually need to get tested for TB and hepatitis. It’s not a quick yes/no switch—talk to your doc about balancing stronger symptom control with these risks.
Methotrexate
If you’re poking around for Hydroxychloroquine alternatives, Methotrexate is probably the first name you’ll hear. It’s a staple for treating rheumatoid arthritis (RA), psoriatic arthritis, and even some cancers. Doctors have trusted it for decades, so it’s got a deep track record.
Methotrexate is usually taken once a week, either as a pill or a quick shot. It works by tamping down your immune system, which helps keep inflammation in check and avoids the joint and organ damage that comes with RA and lupus.
Here’s what’s important: it’s not an overnight fix. Most people start noticing real improvements after about 4-6 weeks. By the 3-month mark, you’ll usually know if it’s doing the job. That’s a different timeline compared to some faster-acting options like Xeljanz.
Pros
- Long history of use, so side effects and risks are well known
- Comes in both pill and injection forms (you choose what you prefer)
- Affordable compared to newer drugs
- Reduces joint damage over the long term in RA and some other autoimmune diseases
- Most insurance plans cover it without fuss
Cons
- Can cause nausea or stomach upsets for some folks
- Needs regular bloodwork to check for liver issues and low white blood cell counts
- Absolutely not safe in pregnancy—your doctor will remind you a lot
- Slow to show results (sometimes up to 3 months)
- Alcohol use has to be limited (methotrexate plus alcohol can mess with your liver)
If you’re looking at switching from Hydroxychloroquine, most rheumatologists reach for Methotrexate because it plays nice with other drugs, offers real disease control for RA, and costs a lot less than biologics. Still, those weekly reminders and blood tests are part of the deal.
| Typical Starting Dose | Time to Effect | Common Monitoring |
|---|---|---|
| 7.5–15 mg weekly | 4–12 weeks | Liver function, blood counts |
Leflunomide
Leflunomide is one of those solid go-to picks for people who can’t take Hydroxychloroquine alternatives like Methotrexate, or who just need something different for their autoimmune issues. It’s mostly prescribed for rheumatoid arthritis, but some docs use it for psoriatic arthritis too. Leflunomide works by stopping immune cells from causing inflammation, which is basically what’s making your joints so sore and swollen in the first place.
Unlike some of the new fancy injectables, you just pop a tablet once a day. It sometimes takes a little while to kick in—usually 4 to 6 weeks, but for some people, it can be up to 12 weeks. That's not as quick as Xeljanz, but definitely faster than waiting for certain biologicals to work.
Pros
- Easy once-daily oral dosing
- Similar effectiveness to Methotrexate for mild-to-moderate rheumatoid arthritis
- No need for self-injections
- Doesn’t cause eye toxicity like Hydroxychloroquine
- Generic is available, so it’s much cheaper than newer treatments
Cons
- Not safe in pregnancy—it can cause birth defects and stays in your body a long time
- Common side effects: upset stomach, weight loss, and hair thinning
- Can mess with your liver, so you’ll need regular bloodwork
- May raise blood pressure and lower your ability to fight infections
- If you want to stop quickly (say, for pregnancy), you’ll need a special "washout" treatment to flush it from your system
If you’re weighing your options between Hydroxychloroquine alternatives, Leflunomide is often picked when Methotrexate isn’t your thing, or if you need something cheap and steady. The blood monitoring can be a hassle, but for many, it’s a fair trade-off. If you’re considering kids, though, this drug can stick around in your system for months, so planning ahead is critical.
| Feature | Leflunomide |
|---|---|
| How taken? | Oral (tablet, daily) |
| Time to see effects | 4-12 weeks |
| Main use | Rheumatoid arthritis, psoriatic arthritis |
| Cost | Low (generic available) |
| Key risks | Liver, pregnancy, blood pressure |
Sulfasalazine
Sulfasalazine is a real workhorse for people with inflammatory arthritis, especially if you're dealing with rheumatoid arthritis (RA) or even certain forms of inflammatory bowel disease. If you can't handle Hydroxychloroquine alternatives like methotrexate, this one often comes up as a solid Plan B. Doctors have been using it for decades, so there's plenty of experience with dosages and what side effects to expect.
This drug works by dampening inflammation in the joints and gut. Researchers think its main trick is blocking the production of certain chemical signals (like cytokines) that trigger swelling and pain. It's often used together with other drugs for even better results—combo therapy is a big thing these days when one drug alone doesn’t cut it.
Pros
- Usually taken as a pill, not an injection. Oral dosing makes life easier for most people.
- Doesn’t cause immunosuppression as deep as some other drugs, so your risk of catching weird infections isn’t sky-high.
- Can help with other symptoms if you have both joint and digestive problems (think Crohn’s or ulcerative colitis).
- Typically affordable and widely available, especially compared to newer treatments.
- Can be used during pregnancy under certain circumstances (but always double-check with your doctor first).
Cons
- You’ve got to deal with regular blood tests—this drug can affect your liver or blood counts.
- Common side effects include upset stomach, headache, and sometimes even yellow-orange soda-colored pee—no joke!
- People with a sulfa allergy can’t take it. That rules some folks out right away.
- Can lower sperm counts temporarily, so men thinking about trying for a baby may want to talk options.
- Takes several weeks to really kick in, so it’s not the best choice if you need super-fast relief.
Here's a quick breakdown of how sulfasalazine compares with other Hydroxychloroquine alternatives for treating RA:
| Drug | Pill or Injection | Typical Onset | Main Use |
|---|---|---|---|
| Sulfasalazine | Pill | 4-12 weeks | RA, IBD |
| Xeljanz (Tofacitinib) | Pill | 1-2 weeks | RA, Psoriatic Arthritis |
| Methotrexate | Pill or Injection | 4-6 weeks | RA |
Always talk with your rheumatologist before swapping or starting anything new—just because sulfasalazine is older doesn’t mean it’s not effective. And if your insurance is being a pain about newer drugs, this one can be much easier to get approved and keep using long-term.
Azathioprine
If you or someone you know deals with autoimmune diseases, there’s a good chance Azathioprine has come up. It’s a well-established immunosuppressant, mostly used in conditions like rheumatoid arthritis, lupus, and even organ transplant patients to prevent rejection. Sometimes, doctors pick Azathioprine when Hydroxychloroquine alternatives are needed, especially for folks with lots of inflammation or if other meds caused too many side effects.
Azathioprine works by tamping down your body’s immune response—so while it doesn’t fix the disease, it helps keep the immune system from attacking your own tissues. It’s usually taken as a pill, once or twice a day, which makes it pretty convenient compared to some drugs that require injections or infusions in a clinic.
Pros
- Oral tablets are easy to take and fit most routines.
- Extensively studied and prescribed—docs are familiar with how to manage it.
- Can be a smart pick for long-term control of autoimmune flare-ups.
- Usually more affordable than new biologic options.
Cons
- Requires frequent blood tests to watch for effects on the liver and blood cells.
- Higher risk for infections due to immune suppression.
- Can cause stomach upset, mouth sores, or rare but serious liver problems.
- Some people have genetic differences (TPMT deficiency) that make side effects more likely—testing before starting may be necessary.
Azathioprine is not a quick-fix option; it can take several weeks—sometimes months—before the full benefit is obvious. If side effects pop up, lowering the dose or switching is common. Statistically, about 1 in 10 people might have to stop Azathioprine due to intolerance or lab changes within the first year.
| Form | Typical Use | Onset | Need for Monitoring |
|---|---|---|---|
| Tablet | RA, lupus, transplant | 1-3 months | Frequent blood tests |
If you hate needles, appreciate affordable options, and don’t mind regular labs, Azathioprine could be a decent alternative when Hydroxychloroquine isn’t cutting it. Of course, every immune suppressor has its quirks—so always talk things through with your rheumatologist first.
Mycophenolate Mofetil
When Hydroxychloroquine alternatives come up in conversation, Mycophenolate Mofetil always gets a solid mention—especially if you’re dealing with tricky autoimmune conditions like lupus or certain types of kidney disease. This med works by slowing down your immune system, so it doesn’t attack your own body. Doctors rely on it a lot for tough cases, particularly if therapies like Methotrexate or Azathioprine haven’t done the trick, or if you have lupus that’s affecting your kidneys (called lupus nephritis).
Unlike Hydroxychloroquine, Mycophenolate Mofetil is a bit stronger. It basically blocks cells in the immune system from copying themselves and causing trouble. If you have moderate or severe lupus, especially with organ involvement, this drug might offer the control Hydroxychloroquine just can’t reach. Some kidney specialists even prefer it now over older heavy-hitters like Cyclophosphamide for keeping kidney function stable without as many hard-core side effects.
Pros
- Very effective for severe lupus (including lupus nephritis) and some vasculitis types
- Works for people who didn’t respond to other Hydroxychloroquine alternatives
- Usually comes as a pill or capsule, so no need for infusions or injections
- Less likely to cause hair loss or infertility compared to some older drugs
Cons
- Suppresses immune defenses, so you catch infections more easily
- Can cause stomach problems—nausea, diarrhea, or cramping are common
- Needs regular blood tests to watch white blood cell counts and liver function
- Not safe for pregnancy—serious risk of birth defects
- Expensive if your insurance doesn’t cover it
If you’re on Mycophenolate Mofetil, don’t skip your monitoring appointments. Doctors will often run blood tests every month at first. And this med really means business—women who could get pregnant need a solid birth control plan in place.
| Side effect | Mycophenolate Mofetil | Hydroxychloroquine |
|---|---|---|
| Nausea/Diarrhea | Up to 36% | Less than 10% |
| Risk of infection | Moderate to high | Low |
| Eye toxicity | Rare | Possible (long-term) |
You’ll want to talk honestly with your doctor to see if Mycophenolate Mofetil is the right move. It’s a powerful option but does come with serious considerations, so it’s not a casual switch.
Cyclophosphamide
Cyclophosphamide isn’t anyone’s first pick, but for certain autoimmune nightmares—think severe lupus or vasculitis that laughs at milder drugs—it can be a real lifesaver. Unlike most daily pills, this one usually comes as an IV drip, especially if fast action is needed. It’s strong enough to reset an out-of-control immune system, but that muscle comes with some pretty serious baggage.
Doctors often roll out cyclophosphamide when other Hydroxychloroquine alternatives just aren’t cutting it. It’s a chemotherapy drug, so while it helps control joint pain and organ-threatening inflammation, it also flattens fast-dividing cells—good for squashing disease, but it can also mess with healthy stuff.
Pros
- Can tackle very severe autoimmune attacks, including severe lupus with kidney involvement.
- Works when most other drugs have failed.
- Usually acts fast, offering hope when nothing else is getting the job done.
- Can be used for a short period to gain control before switching to milder meds.
Cons
- High risk of side effects, including infections, bladder damage, and even future cancers.
- Can seriously lower white blood cells, so regular bloodwork isn't optional—it's mandatory.
- Can impact fertility, which is a big deal for people who still want kids.
- Not convenient: often requires hospital infusions, not home pills.
One important stat if you're comparing drugs: studies show up to 80% of people with severe lupus and kidney problems can get remission or big improvement with cyclophosphamide. But, that power is why it’s saved for tough cases—it makes Hydroxychloroquine alternatives like methotrexate look like baby aspirin in terms of potency, but also risk.
| Side Effect | Frequency |
|---|---|
| Infections | High |
| Low White Blood Cells | Common |
| Bladder Issues | Moderate |
| Nausea/Vomiting | Very Common |
| Fertility Problems | Moderate to High |
If your doctor brings up cyclophosphamide, it means things are serious—don’t be afraid to ask about every single risk and what to expect with monitoring. For a small group of people facing life-threatening autoimmune crises, this drug can be a total game-changer.
Rituximab
Rituximab stands out as a powerful alternative, especially if regular meds like Hydroxychloroquine or Methotrexate aren’t cutting it. It’s a biologic drug, which just means it’s made from living cells and targets the immune system differently than traditional pills. This med goes right after a type of white blood cell called B-cells, knocking them down to help with inflammatory conditions like rheumatoid arthritis and some forms of lupus.
It’s not a daily tablet—instead, Rituximab is given as an IV infusion, usually at a clinic. Most people get it in two doses a few weeks apart and then not again for months. So if you hate swallowing pills, this could be a plus.
Pros
- Can be very effective in patients who haven’t done well on other meds.
- Usually just a couple infusions per year mean fewer office visits than weekly meds.
- Shown to help people with severe or hard-to-treat rheumatoid arthritis, especially when paired with Methotrexate.
- Not linked to eye toxicity like Hydroxychloroquine.
Cons
- Infusions can take several hours and need to be done in a medical setting.
- Common risks: infections, low blood cell counts, infusion reactions (rash, chills, sometimes fever).
- Usually not a first-line treatment—it’s for folks who’ve already tried other options.
- May not work for everyone and can be expensive without good insurance.
Just so you have a real-world idea, a 2023 registry showed that about 40–50% of rheumatoid arthritis patients who failed other drugs saw strong improvements with Rituximab. Most people report relief after a few months, but it’s not instant.
| How it’s given | Who it’s for | Main risks |
|---|---|---|
| IV infusion (every 6-12 months) | People not helped by standard RA or lupus meds | Infections, infusion reactions |
Bottom line: Rituximab isn’t for everyone, but if your symptoms are stubborn and other Hydroxychloroquine alternatives haven’t worked, it’s worth a serious look. Just be sure to chat with your rheumatologist about all the pros and cons.
Belimumab
Belimumab is probably one of the more modern options if you’re looking for Hydroxychloroquine alternatives—especially for people dealing with lupus. It’s not a pill you pick up at the pharmacy; this one is a biologic that usually gets given as an infusion, though there’s a version you can inject at home. The main thing it does? It blocks part of your immune system called BLyS, which can be running too hot in lupus and causing organ damage.
What a lot of patients like right away is that Belimumab is actually made for treating lupus, rather than using drugs off-label. The data backing it is solid: in large studies, adding Belimumab to standard lupus treatments cut down on flare-ups and let some folks reduce their steroid dose. That’s a big deal if you’re tired of steroid side effects. In fact, patients on Belimumab had about a 10-15% improved response compared to regular therapy alone.
Pros
- Specifically designed for lupus, not just repurposed from something else.
- Can decrease disease flare-ups and help patients cut back on steroids.
- Is available both as an IV infusion (monthly) or as a shot you give yourself at home (weekly).
- Tends to have milder side effects compared to older immunosuppressants.
Cons
- Expensive if you don’t have solid insurance coverage.
- Doesn’t work for everyone—about a third of people don’t see much improvement.
- It’s only FDA-approved for lupus and some kidney issues, so not helpful for other autoimmune diseases.
- Can make patients more likely to pick up infections, especially early on.
Here’s a simple breakdown for quick comparison:
| Belimumab Facts | Details |
|---|---|
| How taken | IV infusion (monthly) or SubQ injection (weekly) |
| Best for | Lupus, lupus kidney issues (not for other autoimmune) |
| Side effect alerts | Increased risk of infection, infusion reactions |
| Year FDA approved | 2011 |
If you’ve tried Hydroxychloroquine and your lupus is still active or the side effects are a dealbreaker, Belimumab is worth bringing up with your specialist. Just make sure to talk about the cost, because prices can be steep without coverage.
Abatacept
Abatacept is a newer kind of treatment that goes after the root causes of inflammation in autoimmune diseases like rheumatoid arthritis (RA). Unlike some older options, it doesn’t just block symptoms—it slows down your immune system by stopping certain cells from getting switched on and causing joint swelling and pain. If Hydroxychloroquine alternatives are on your mind because your RA’s too stubborn or you’re not seeing results, Abatacept is worth talking about with your rheumatologist.
Doctors usually give Abatacept either as a monthly IV drip at a clinic or as a weekly shot you can do yourself at home. Most people start noticing changes after a few weeks, but it can take a few months for full results.
Pros
- Targets the immune system in a different way, which can help if other drugs have failed.
- Less likely to cause major stomach issues than methotrexate or leflunomide—big win if you hate nausea.
- Available as both an IV drip and an injection (so you can pick what fits your life).
- Can be used in folks who have a history of liver problems, since it’s not hard on the liver.
Cons
- There’s a bigger risk for serious infections since it quiets your immune system—think pneumonia or even shingles.
- Costs can be high, especially in the U.S.; insurance coverage varies a lot.
- Some people get headaches or feel dizzy after the infusion.
- Not for people with certain lung issues or those with a history of frequent infections.
One nugget worth noting: A real-world observational study in 2022 found that patients who switched from Hydroxychloroquine alternatives to Abatacept for tough RA saw about 40% lower rates of new joint damage at the one-year mark. That’s no small thing if you’re worried about long-term damage.
Tip: If you get regular infections or your immune system is already shaky, it's crucial to run bloodwork and talk openly with your specialist before making this switch. Bring up vaccination status too—many live vaccines aren’t safe once you’re on Abatacept.
Conclusion & Summary Table
Choosing between Hydroxychloroquine alternatives depends a lot on your disease, other health issues, and what you want from treatment—like a pill versus an injection, faster relief, or fewer side effects. There’s no one-size-fits-all answer. Your doctor will usually tailor the choice by weighing your specific symptoms, lab results, and risk factors like infections or heart problems. For example, Xeljanz (Tofacitinib) works fast and is easy to take, but isn’t great if you're at risk for infections or have a heart condition. Immune-targeting drugs like Rituximab are usually saved for folks who haven’t done well with anything else. Affordable, older options like Methotrexate still work well for lots of people, though the side effect profile is different.
Don’t be surprised if your doctor wants regular bloodwork or checks for infections on these drugs. Some require more monitoring than others—especially the stronger immunosuppressants. Always speak up about any weird symptoms, and don’t hesitate to bring this comparison to your next appointment for a real talk.
Here’s a quick breakdown you can use to compare:
| Name | Main Use | How It's Taken | Quick Relief? | Common Downsides |
|---|---|---|---|---|
| Xeljanz (Tofacitinib) | RA, Psoriatic arthritis | Oral pill | Yes | Infection risk, heart risk, cost |
| Methotrexate | RA, Lupus | Pill or injection | Slow/Medium | Liver toxicity, nausea, labs needed |
| Leflunomide | RA | Pill | Medium | Liver problems, diarrhea |
| Sulfasalazine | RA, Inflammatory arthritis | Pill | Slow | Rash, stomach upset |
| Azathioprine | Lupus, Autoimmune conditions | Pill | Medium | Infection risk, labs needed |
| Mycophenolate Mofetil | Lupus (esp. kidneys) | Pill | Medium | Stomach upset, infection risk |
| Cyclophosphamide | Severe lupus, Vasculitis | IV/Oral | Fast | Serious side effects, cancer risk |
| Rituximab | RA, Severe autoimmune | IV | Medium | Infusion reactions, infection |
| Belimumab | Lupus | IV/Self-injection | Medium | Infection, nausea |
| Abatacept | RA, Juvenile arthritis | IV/Self-injection | Medium | Headache, infection |
If you’re trying to choose a Hydroxychloroquine alternative, use this table as a cheat sheet—but always expect your doctor to factor in your big picture and keep a close eye on any side effects along the way.