Can I Stop Taking Methotrexate for Rheumatoid Arthritis?

Stopping methotrexate is possible, but doing so without medical guidance carries a real risk of disease flare. Studies show that roughly four in ten people who discontinue methotrexate after achieving low disease activity experience a flare within six months, and that risk rises the longer they remain off the drug. The decision is rarely as simple as “stop or continue,” though. It depends on why you want to stop, whether you are on other medications alongside methotrexate, how long your disease has been quiet, and what your rheumatologist sees in your bloodwork and joints.

Why People Want to Stop

Methotrexate is the most widely used drug in the world for rheumatoid arthritis and has been the backbone of treatment for decades.¹ Current guidelines recommend it as the first medication to try, often alongside folic acid, with escalation to other drugs only if methotrexate alone is not enough.² It works well for many people, but that does not mean it is easy to live with.

About 30% of patients eventually stop methotrexate because of side effects.³ Nausea, fatigue in the day or two after taking it, mouth sores, and liver enzyme elevations are common complaints. Some people tolerate the drug fine for years but grow tired of weekly blood monitoring or simply wonder whether they still need it, especially when their joints have felt good for a long stretch. Others face specific situations that force the question: pregnancy planning, upcoming surgery, or a need for certain vaccines.

The Flare Risk Is Real but Not Universal

The biggest concern with stopping methotrexate is that rheumatoid arthritis can come roaring back. In a study of patients who had been in low disease activity on long-term methotrexate, just under half experienced a flare within six months of discontinuation, with a median time to flare of about three months.⁴ That is a coin-flip, and it is sobering when you consider that each flare can cause lasting joint damage.

A review of multiple studies on methotrexate tapering and withdrawal confirmed that stopping disease-modifying drugs entirely carries a definite risk of flare, though researchers noted it was not always clear how much of that risk belonged specifically to methotrexate versus other drugs patients may have also been taking.⁵ The honest assessment is that roughly half of people who stop will do well, and roughly half will not. The trouble is figuring out in advance which group you fall into.

Tapering Gradually Versus Stopping All at Once

You might assume that slowly reducing the dose would be safer than quitting outright. The evidence on this is surprisingly mixed. Data from a large Dutch registry tracked over 1,300 rheumatoid arthritis patients on both methotrexate and a biologic drug. Among those who tapered methotrexate gradually, about 21% relapsed within six months. Among those who stopped methotrexate completely, the relapse rate was similar: 21% at six months and 24% at twelve months. On average, both groups maintained disease activity scores comparable to patients who never changed their methotrexate dose at all.⁶

These numbers look reassuring, but there is a crucial detail: those patients were also on a biologic. That second drug was likely doing a lot of the heavy lifting in keeping their disease under control. When methotrexate is your only medication, the stakes of stopping are higher. Whether you taper or stop abruptly, your rheumatologist should be monitoring you closely, typically with bloodwork and clinical assessments every few weeks during the transition.

The Special Case of Biologic Combination Therapy

Many people with rheumatoid arthritis take methotrexate alongside a biologic drug like adalimumab, etanercept, or infliximab. In this scenario, stopping methotrexate raises a less obvious concern: your immune system may start producing antibodies against the biologic itself.

Methotrexate suppresses the immune response broadly, and one of its side benefits is that it reduces the formation of anti-drug antibodies against biologics. In one study of patients on long-term adalimumab, the percentage who developed detectable anti-drug antibodies jumped from 18% to 68% when methotrexate was tapered and stopped.⁷ While those antibodies did not immediately tank the biologic’s blood levels, patients who developed them appeared to clear the biologic drug faster when the biologic itself was later reduced. In practical terms, dropping methotrexate while staying on a biologic might not cause an immediate problem, but it could set the stage for the biologic to stop working over time.

The DREAM registry data showed that tapering or discontinuing methotrexate had no measurable effect on how long patients stayed on their biologic over the study period.⁶ So the immunogenicity concern is real but may take longer to matter than a typical study follows patients. If you are on a biologic and considering dropping methotrexate, the conversation with your rheumatologist should specifically include this risk.

Who Is Most Likely to Stay in Remission

Researchers have tried to identify the people who can safely stop or reduce methotrexate without flaring. The predictors that keep emerging are not surprising but are worth knowing. A cohort study at a national referral center found that lower disease activity at the time of the decision, a normal inflammatory marker level (measured by a blood test called ESR), having five or fewer tender joints, and being at a healthy weight were all significantly associated with better outcomes on methotrexate monotherapy.⁸ The pattern holds across studies: the quieter your disease is before you attempt a change, the better your odds.

Duration of remission matters too. Someone who has been in sustained remission for a year or more is generally a better candidate for tapering than someone who reached low disease activity just a few months ago. And while no blood test or imaging scan can guarantee that you will stay well after stopping, these factors help your rheumatologist make a more informed judgment rather than a guess.

What Happens If You Flare After Stopping

One of the most reassuring findings in this area is that restarting methotrexate usually works. An analysis of two randomized trials looked at patients who stopped methotrexate for four weeks. Their disease activity rose during the gap, as expected, but after restarting the drug, scores returned to baseline.⁹ This is important psychologically. Many people fear that if they stop and flare, they will never get back to where they were. The evidence suggests that short interruptions do not permanently change the drug’s effectiveness.

That said, a short four-week pause is very different from stopping for six months or a year. The longer the gap, the more joint damage a sustained flare can cause, and the harder it can be to regain the same level of control. The principle that methotrexate can “recapture” remission holds best when the interruption is caught and addressed early, which is another reason close monitoring during any attempt to stop is critical.

Stopping for Pregnancy

Pregnancy is one situation where stopping methotrexate is not optional. Methotrexate taken after conception is clearly linked to miscarriage and major birth defects, and current recommendations call for stopping it at least three months before trying to conceive.¹⁰ This applies to both women and, per most guidelines, men planning to father a child, though the evidence for paternal risk is less definitive.

The challenge is that rheumatoid arthritis can flare during the pre-conception washout period and during pregnancy itself. A study specifically examining pregnancy outcomes in RA patients who discontinued methotrexate confirmed that the stop is medically necessary but emphasized the need for a transition plan to pregnancy-compatible medications like hydroxychloroquine or low-dose corticosteroids to manage symptoms during this window.¹¹ If you are thinking about pregnancy, bring it up with your rheumatologist well before you want to conceive so the transition can be planned rather than improvised.

Pausing for Vaccinations

A more recent reason to temporarily stop methotrexate is vaccination. Because the drug dampens immune responses, it can blunt your body’s reaction to certain vaccines. The VROOM trial found that pausing methotrexate for two weeks around a COVID-19 booster dose significantly improved antibody responses, and the benefit lasted at least six months. The trade-off was a temporary uptick in disease flares, though most were mild and self-managed.¹²

A separate study in older RA patients found an even starker difference: among those who continued methotrexate through vaccination, about a quarter failed to mount any meaningful antibody response, compared with just 3% of those who paused the drug.¹³ This finding held even in patients on methotrexate alone, ruling out the possibility that other medications explained the gap. The current thinking among rheumatologists is that a brief pause around vaccination is worth considering on a case-by-case basis, especially for people who are older or at higher risk of severe infection. It is not a blanket recommendation, though, because even a two-week break can trigger a flare in someone whose disease is not fully stable.

When Side Effects Force the Decision

Sometimes you do not get to choose whether to stop methotrexate. Liver toxicity, for example, can develop gradually and require discontinuation. A case series examining methotrexate-induced liver injury found that hepatotoxicity resolved in all cases after the drug was stopped, even in patients who had complicating factors like diabetes or kidney disease.¹⁴ That is good news for people worried about lasting damage from the drug itself, but it leaves the question of what comes next for their arthritis.

When methotrexate has to go because of toxicity or intolerance, rheumatologists typically turn to other conventional disease-modifying drugs like sulfasalazine, leflunomide, or hydroxychloroquine, sometimes used in combination. A study tracking patients started on triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) found that roughly 38% stopped at least one of the three drugs because of an adverse event, with others dropping a drug because of remission or poor response.¹⁵ The point is that methotrexate is not the only game in town. If you need to stop, there are other options, including biologics and targeted synthetic drugs, though each comes with its own trade-offs.

Cost Considerations When Changing Treatment

Methotrexate is one of the cheapest drugs in rheumatology, and switching to a biologic or a newer targeted therapy can dramatically increase costs. Interestingly, one study of patients who started the targeted drug tofacitinib alongside methotrexate found that those who later discontinued methotrexate had similar treatment persistence, adherence, and effectiveness at twelve months compared with those who kept taking both. Arthritis-related healthcare costs were actually higher in the group that stayed on methotrexate, likely because the continued-methotrexate group required more monitoring and had more office visits.¹⁶ This does not mean stopping methotrexate saves money across the board, because the context was specific to patients already on an expensive second drug. But it does suggest that the assumption “staying on everything is always better” is not always backed by the economics.

How to Have the Conversation With Your Rheumatologist

If you are considering stopping methotrexate, the worst approach is to simply stop taking it on your own. Abrupt unsupervised discontinuation leaves no one watching for early signs of flare, which means joint damage can accumulate before you realize something has gone wrong. Instead, come to your appointment prepared with a few specifics: how long you have been in remission, what side effects are bothering you, and whether your reason for stopping is temporary (like vaccination or pregnancy) or permanent (intolerance, fatigue with treatment).

Your rheumatologist will likely want recent lab work and a joint exam before making a plan. If the decision is to try tapering, expect a slow reduction over weeks or months, with visits every four to eight weeks to check disease activity scores and inflammatory markers. If you are also on a biologic, the conversation should explicitly address whether the biologic alone can hold your disease in check and whether anti-drug antibody risk changes the calculus.

Some people do successfully stop methotrexate and stay well for years. Others stop, flare within weeks, and restart without incident. The evidence is clear that stopping is not automatically dangerous, but it is also clear that it is not risk-free. The people who fare best are those who make the decision with full information, close follow-up, and a clear plan for what to do if things go sideways.