Methotrexate (MTX) is a Disease-Modifying Antirheumatic Drug (DMARD) used to treat Rheumatoid Arthritis (RA), a chronic autoimmune condition where the immune system attacks healthy joint tissue. The decision to stop taking MTX is a serious medical consideration requiring specialized guidance. Stopping this medication without a rheumatologist’s supervision can lead to a rapid return of disease activity, so the decision must always be made collaboratively using objective measures.
The Purpose of Methotrexate in RA Therapy
Methotrexate functions as a foundational treatment for RA, working to modulate the overactive immune system responsible for joint inflammation and destruction. It is an immunosuppressant that achieves its anti-inflammatory effect by dampening inflammatory signaling pathways.
The drug’s primary role is to actively change the course of the disease, not just relieve symptoms. By controlling chronic inflammation, MTX helps patients achieve and maintain sustained remission or low disease activity. The long-term objective of this therapy is to prevent progressive joint erosion and preserve physical function, since joint damage can occur rapidly in uncontrolled RA. MTX is the standard-of-care DMARD, often serving as the first-line therapy before or alongside biologic agents.
Medical Criteria for Considering Discontinuation
Discontinuation can only be considered after achieving a deep, prolonged state of disease control. The prerequisite is sustained clinical remission, meaning minimal or no disease activity for at least six to twelve months. This state is determined by objective clinical and laboratory measures, not simply by the patient feeling well.
Remission is often measured using the Disease Activity Score of 28 joints (DAS28), where a score less than 2.6 indicates remission. The decision is also informed by blood work, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), which measure systemic inflammation. Other reasons for discontinuation include severe, unmanageable side effects or planning for pregnancy, which requires both men and women to stop MTX use at least three months before attempting conception.
Risks of Abruptly Stopping Treatment
Stopping methotrexate abruptly carries a substantial and immediate risk of a disease flare. This rebound occurs because the medication’s protective anti-inflammatory effect is suddenly withdrawn. Studies have shown that even a short, four-week discontinuation of MTX can transiently increase the risk of a flare and disease activity.
The risk of a flare is significantly higher with abrupt cessation compared to gradual tapering. Up to 44% of patients who achieved low disease activity may experience a flare within six months of discontinuing the drug. Flares represent a period of unchecked inflammation that can accelerate structural joint damage, potentially leading to irreversible bone erosion and disability.
The Supervised Process of Tapering
If the medical criteria for sustained remission are met, discontinuation involves a gradual reduction known as tapering. This slow step-down approach is conditionally recommended over abrupt cessation to minimize the risk of a disease flare, allowing the body to adjust to lower drug levels while the doctor monitors for any return of disease activity.
There are two common tapering methods. One involves reducing the weekly dose by 2.5 to 5 milligrams, or by half, and maintaining that reduced dose for two to three months before further change. The alternative is keeping the dose the same but extending the interval between doses, such as changing from weekly to every two weeks. Close monitoring is maintained throughout this period, involving clinical assessments and laboratory tests every one to three months. If disease activity, such as joint swelling or elevated inflammatory markers, returns during the taper, the previous effective dose must be immediately reinstated to regain disease control.