For millions living with rheumatoid arthritis, the question of whether they can ever stop treatment is one of the most pressing—and frightening—they will face.
Rheumatoid arthritis (RA) is more than just occasional joint pain—it's a chronic autoimmune condition where the body's immune system mistakenly attacks its own tissues, primarily targeting the lining of the joints. This leads to painful swelling, joint damage, and eventually physical disability. For decades, treatment options were limited, with many patients experiencing progressive joint destruction despite available therapies.
Immune system attacks joint tissues
Leads to swelling and potential disability
Revolutionized RA care in recent decades
The landscape transformed dramatically with the introduction of advanced targeted treatments, including biologic disease-modifying antirheumatic drugs (bDMARDs) like tumor necrosis factor inhibitors (TNFis) and, more recently, targeted synthetic DMARDs like tofacitinib. These medications have revolutionized RA care, enabling many patients to achieve clinical remission or at least low disease activity—states where symptoms are minimal or undetectable.
Yet these breakthroughs come with significant challenges: high costs, potential side effects, and the inconvenience of regular injections or infusions. This has led to one of the most important questions in modern rheumatology: Can these medications be safely discontinued once patients achieve stable remission? New research is providing crucial answers.
Before examining discontinuation outcomes, it's essential to understand the key medications involved.
Tumor Necrosis Factor Inhibitors (TNFis) were the first biologics approved for RA. They work by blocking TNF, a protein that promotes inflammation. Examples include etanercept, adalimumab, and infliximab.
Janus Kinase (JAK) Inhibitors like tofacitinib represent a newer class of oral medications. They work inside cells to block multiple inflammatory signaling pathways. Their convenience as oral tablets made them quickly popular after approval.
Both medication types are typically used in combination with conventional DMARDs like methotrexate, but when—and in whom—can treatment be safely scaled back or stopped?
The Oral Surveillance study, which specifically compared the safety of tofacitinib to TNF inhibitors, generated crucial data on what happens when patients discontinue these therapies. While the original study focused on safety outcomes, subsequent analyses have examined discontinuation patterns and their clinical implications.
A comprehensive pooled analysis drawn from two Canadian RA registries (the Ontario Best Practices Research Initiative and Rhumadata) followed patients who either started TNFis or tofacitinib between June 2014 and December 2019 3 .
The study included 1,318 RA patients—825 starting TNFi therapy and 493 starting tofacitinib 3 .
Researchers tracked these patients from treatment initiation until discontinuation, death, loss to follow-up, or the end of the study period.
The researchers used sophisticated statistical methods, including propensity score stratification and weighting, to balance characteristics between the treatment groups and reduce potential bias in this observational study 3 .
The results provided unprecedented insights into real-world treatment discontinuation patterns:
TNFi Discontinuation
Tofacitinib Discontinuation
Overall Discontinuation Rate
| Outcome Measure | TNF Inhibitors | Tofacitinib | Statistical Significance |
|---|---|---|---|
| Overall discontinuation | 37.5% | 36.7% | Not significant |
| Discontinuation due to ineffectiveness | Similar rate | Similar rate | Not significant |
| Discontinuation due to adverse events | Lower rate | Higher rate | Statistically significant |
These patterns remained consistent even when the analysis was restricted to patients using these treatments as first-line advanced therapy 3 .
While understanding why patients stop medication is important, what happens after discontinuation may be even more critical for clinical decision-making.
A prospective study from Japan followed 97 RA patients who discontinued bDMARDs or tofacitinib after maintaining remission or low disease activity for at least 48 weeks 6 . The findings revealed a crude incidence rate of disease flare of 0.36 per person-year 6 .
The median time to flare was 1.6 years, with cumulative flare probabilities estimated at 45% at 1 year, 64% at 3 years, and 80% at 5 years after discontinuation 6 .
Importantly, the Japanese study also examined structural joint damage, finding that 87.1% of patients who maintained remission for 3 years after discontinuation showed no or minimal radiological progression 6 . This suggests that even if disease activity returns, structural damage may not rapidly progress during drug-free remission.
of flare patients rapidly regained disease control within one month after reintroducing previous treatment 6
Research has identified several factors that predict better outcomes after treatment discontinuation:
Patients who began treatment earlier in their disease course had lower flare risk after discontinuation 6
Maintaining remission or low disease activity for a longer period before discontinuation reduces flare risk 6
Patients without a history of failing previous biologic treatments have better success with discontinuation 6
Continuing methotrexate while stopping advanced therapy appears beneficial
Higher dosage → Worse outcomes for discontinuation
| Predictive Factor | Impact on Discontinuation Success |
|---|---|
| RA duration at treatment start | Shorter duration → Better outcomes |
| Period of remission before discontinuation | Longer period → Better outcomes |
| Previous bDMARD failures | No failures → Better outcomes |
| Concomitant methotrexate | Continued use → Better outcomes |
| Steroid dosage | Higher dosage → Worse outcomes |
The evidence suggests that discontinuation of advanced RA therapies is a feasible strategy for selected patients, particularly those with earlier-treated disease who have maintained longer periods of remission 6 . While flare rates are substantial, reintroduction of previous therapy is generally effective at rapidly regaining disease control 6 .
The choice between TNF inhibitors and tofacitinib involves trade-offs: while both show similar overall discontinuation rates, tofacitinib appears associated with a higher rate of discontinuation due to adverse events 3 .
This nuanced understanding helps patients and clinicians make more informed decisions about treatment plans tailored to each individual's unique circumstances and preferences.
Note: This article synthesizes findings from multiple clinical studies to provide a comprehensive overview of current evidence regarding treatment discontinuation in rheumatoid arthritis. As with any medical information, consult with your healthcare provider before making changes to your treatment regimen.