The Treatment Dilemma: When Can RA Patients Safely Stop Advanced Therapies?

For millions living with rheumatoid arthritis, the question of whether they can ever stop their medication is one of both hope and uncertainty.

Exploring the evidence on discontinuing advanced therapies for rheumatoid arthritis patients in remission

Imagine achieving complete relief from rheumatoid arthritis symptoms—the morning stiffness gone, the joint pain vanished, the fatigue lifted. Now imagine facing a difficult decision: continue taking expensive medications with potential side effects, or risk stopping treatment and possibly undoing all that progress.

This is the very dilemma confronting rheumatologists and their patients every day. Biological drugs and targeted synthetic medications have revolutionized RA treatment, but the question of when—and if—treatment can be safely reduced or stopped remains intensely debated in the medical community ¹ ⁶ .

Remission in RA: What Does It Really Mean?

Before understanding treatment discontinuation, we must first understand the treatment goal: remission.

Clinical Remission

When signs and symptoms of RA have largely or completely disappeared. Doctors use specific measures like DAS28 (Disease Activity Score in 28 joints) or CDAI (Clinical Disease Activity Index) to determine if someone has reached this state ¹ ⁶ .

Low Disease Activity (LDA)

The next best outcome, where minimal disease activity remains but doesn't significantly impact daily life ¹ ⁶ .

Sustained Remission

This is the key to considering treatment changes. Most studies require patients to maintain remission or LDA for at least 6-12 months before contemplating reduction or discontinuation of advanced therapies ¹ ⁵ .

The fundamental question researchers are exploring is whether remission represents a temporary state controlled by medication, or a more durable condition that might persist even after treatment withdrawal.

To Stop or Not to Stop? What the Evidence Reveals

Numerous studies have investigated the outcomes of discontinuing advanced RA therapies, with remarkably consistent findings across different medications and patient populations.

The High Risk of Complete Withdrawal

Multiple studies demonstrate that complete discontinuation of TNF inhibitors or tofacitinib carries a high risk of disease flare:

A 2022 Japanese study followed 97 patients who stopped treatment after sustained remission. The flare rate was 45% at 1 year, increasing to 64% at 3 years, and 80% at 5 years ¹ ⁶ .
The 2025 ARCTIC REWIND trial compared continued TNF inhibitor treatment versus tapering to withdrawal. Only 25% of patients in the discontinuation group remained flare-free after three years, compared to 85% in the continued treatment group ² .
A 2023 Chinese randomized trial testing tofacitinib discontinuation found only 20.5% of patients maintained low disease activity at 6 months after stopping, compared to 95.1% who continued treatment ⁵ .

Dose Reduction: A Promising Middle Ground

While complete discontinuation shows high failure rates, dose reduction may offer a more viable approach:

The 2023 Chinese trial found that reducing tofacitinib from 5 mg twice daily to 5 mg once daily maintained low disease activity in 64.3% of patients at 6 months—significantly better than the 20.5% with complete withdrawal ⁵ .
A Cochrane systematic review of 14 studies concluded that fixed-dose reduction of anti-TNF agents was comparable to continuing standard dosing regarding disease activity and function ⁴ .

Comparing RA Treatment Strategies After Achieving Remission

Strategy	Percentage Maintaining Disease Control	Key Advantages	Key Limitations
Continue Full Dose	85-95% after 6 months ² ⁵	Highest probability of maintaining remission	Ongoing cost, potential side effects, possible overtreatment
Dose Reduction	64-75% after 6 months ⁴ ⁵	Reduces cost and potential side effects while maintaining good disease control	Moderate risk of disease flare
Complete Discontinuation	20-25% after 6 months ² ⁵	Eliminates medication costs and side effects completely	High risk of disease flare requiring restart of treatment

A Landmark Trial: The ARCTIC REWIND Study

The 2025 ARCTIC REWIND trial provides some of the most rigorous evidence to date on treatment discontinuation. This multicenter randomized trial followed patients with RA in remission for ≥12 months who were taking stable TNF inhibitor therapy ² .

Methodology

Study Design: Open-label, noninferiority trial
Participants: 99 randomized patients, 92 received allocated therapy, 80 completed three-year follow-up
Groups: Randomized 1:1 to either taper TNF inhibitor to withdrawal or continue stable treatment
Primary Endpoints: Flare-free survival and radiographic progression over three years
Patient Profile: Mean baseline Disease Activity Score was 0.8 (indicating deep remission), with 90% using conventional synthetic DMARD co-medication ²

Results and Implications

The findings were striking in their clarity:

Flare-free survival: Only 25% (95% CI 13%-38%) remained flare-free in the discontinuation group versus 85% (95% CI 70%-93%) in the continued treatment group ² .
Hazard ratio for flare: 9.4 (95% CI 3.9-22.8), meaning those who discontinued were over 9 times more likely to experience a flare ² .
Radiographic progression: No statistically significant difference between groups, suggesting that even if clinical symptoms returned, joint damage progression wasn't significantly worse in the discontinuation group over three years ² .

ARCTIC REWIND Trial Results at 3 Years

Outcome Measure	Tapering to Withdrawal Group	Stable Treatment Group	Statistical Significance
Flare-free Survival	25% (13%-38%)	85% (70%-93%)	P < 0.0001
Hazard Ratio for Flare	9.4 (3.9-22.8)	Reference (1.0)	P < 0.0001
Radiographic Progression	15% (6/41)	8% (3/38)	P = 0.3 (not significant)
Adverse Events	81%	89%	Not reported

25%

Flare-free survival in discontinuation group

85%

Flare-free survival in continued treatment group

Who Can Successfully Stop Treatment?

Research has identified several factors that predict better outcomes after treatment discontinuation:

Factors Favoring Successful Discontinuation

Shorter RA duration at start of advanced therapy: Patients who received earlier intervention had better outcomes after discontinuation ¹ ⁶ .
No prior failure of other bDMARDs: Patients without a history of failing multiple advanced therapies were more likely to maintain remission ¹ ⁶ .
Longer period of remission before discontinuation: The longer the remission was maintained before stopping treatment, the better the outcomes ¹ ⁶ .
Type of discontinued drug wasn't a significant predictor: The study found similar outcomes regardless of which specific TNF inhibitor or tofacitinib was discontinued ¹ ⁶ .

Predictors of Successful Treatment Discontinuation

Predictor	Favors Successful Discontinuation	Evidence Source
Disease Duration	Shorter duration at start of advanced therapy ¹ ⁶	Mori et al. 2022
Treatment History	No prior failure of other bDMARDs ¹ ⁶	Mori et al. 2022
Stability of Remission	Longer period of sustained remission before discontinuation ¹ ⁶	Mori et al. 2022
Conventional DMARD Use	Continued use of methotrexate or similar drugs ²	ARCTIC REWIND 2025

The Scientist's Toolkit: Measuring RA Treatment Success

Rheumatologists use specific tools and measures to guide treatment decisions:

Disease Activity Scores (DAS28)

Composite measure incorporating tender/swollen joint counts, patient global assessment, and inflammatory markers ⁵ .

Function: Primary outcome measure in most clinical trials.

Clinical Disease Activity Index (CDAI)

Simplified measure using only clinical findings without laboratory tests ¹ ⁶ .

Function: Quick assessment of disease status during clinical visits.

Modified Total Sharp Score (mTSS)

Detailed radiographic assessment of joint damage ¹ ⁶ .

Function: Measures structural damage progression, crucial for long-term outcomes.

Health Assessment Questionnaire (HAQ)

Patient-reported measure of physical function ³ ⁵ .

Function: Assesses real-world impact of RA on daily activities.

Conclusion: A Personalized Path Forward

The evidence clearly indicates that while complete discontinuation of advanced RA therapies carries a high risk of disease flare for most patients, dose reduction represents a promising middle ground that balances risk reduction with medication burden ⁴ ⁵ .

Critically, studies consistently show that when flares do occur after discontinuation, restarting the previous treatment typically regains disease control rapidly—often within one month ¹ ⁶ . This safety net may make attempting discontinuation more feasible for suitable candidates.

The future of RA treatment de-escalation lies in better predicting which patients can successfully reduce or stop therapy. As research advances, the decision to continue, reduce, or stop advanced therapies will increasingly become a personalized choice based on disease characteristics, treatment history, and patient preferences—moving us closer to truly precision medicine in rheumatoid arthritis.

The journey toward treatment discontinuation represents not a failure of therapy, but its greatest success—the possibility of sustained wellness even without continuous intervention.

Personalized Approach

Treatment decisions based on individual patient factors

Dose Reduction

Promising middle ground between continuation and discontinuation

Continued Research

Better predictors for successful treatment de-escalation