Methotrexate Stayed in Place When Biologic or Targeted Therapy Began in Rheumatoid Arthritis
In routine rheumatoid arthritis care, methotrexate often remains the anchor drug even after escalation to a biologic or targeted synthetic DMARD. The 2-year STRATEGE2 cohort shows how firmly that practice has taken hold: methotrexate was continued at the start of b/tsDMARD therapy in 97.7% of participants, reflecting a treatment pattern that still treats the conventional agent as the backbone rather than a disposable bridge.
This matters because the study population was not composed of treatment-naive patients or people with mild disease. These were adults with established rheumatoid arthritis who had already been treated with methotrexate for at least 3 months and still required escalation because disease activity remained active. In other words, the cohort reflects the clinical moment when rheumatologists decide whether to preserve methotrexate, change route, adjust dose, or stop it altogether when introducing a more advanced therapy.
Baseline Disease Burden Was Still Substantial at Escalation
At enrollment, 173 participants had a mean disease duration of 5.6 years, with wide variability around that average, and a mean DAS28 of 4.3. That level of disease activity sits well above remission and is consistent with ongoing inflammatory burden despite prior conventional therapy. Two-thirds had already been on methotrexate for more than a year, suggesting a population in whom the drug had already been tried long enough to establish tolerance, adherence, and partial effectiveness before escalation was triggered.
The methotrexate dose at baseline averaged 18.8 mg weekly, with a median of 20.0 mg, and 72.3% were receiving the drug subcutaneously. The route is clinically meaningful. Subcutaneous administration is often selected when oral methotrexate is insufficient, when absorption is a concern, or when clinicians want to push dose intensity without losing tolerability. In practice, it signals a deliberate effort to preserve methotrexate exposure rather than abandon it.
Continuation Dominated the Early Combination Phase
When the first biologic or targeted synthetic DMARD was introduced, methotrexate was almost universally carried forward. At 12 months, 83.2% of participants were still on methotrexate. Among the subgroup with stable therapy, 39.9% retained the same dose and route, with a 95% confidence interval of 32.5% to 47.6%.
A single sentence captures the practical reality: methotrexate was usually not stopped at the point of escalation.
Discontinuation did occur, but the reasons were familiar rather than mysterious. Participant choice and adverse events accounted for most of the stopping decisions. That pattern is clinically important because it suggests the barrier to long-term combination therapy is less about immediate loss of efficacy than about real-world tolerability, preferences, and the cumulative burden of chronic treatment. In inflammatory arthritis, adherence often turns on the everyday experience of the drug, not on abstract pharmacology.
Disease Activity Fell Sharply Over Two Years
By 24 months, mean DAS28 had fallen by 2.0 points from baseline, with a standard deviation of 1.3. The magnitude of that decline is consistent with meaningful disease control rather than a marginal shift in symptom reporting. Sixty-six percent of participants had achieved remission at M24, while EULAR response classification showed 65.2% with a good response, 19.1% with a moderate response, and 15.6% with an inadequate response.
Those response proportions suggest that the treatment strategy was effective for most, though not all, patients. From a bedside perspective, the data reinforce a familiar principle in rheumatoid arthritis management: escalation to advanced therapy can produce strong control even in people who arrive at the decision point with persistent activity after methotrexate. The sustained improvement also supports the idea that methotrexate continuation did not interfere with the expected benefit of the new agent in this cohort.
Biologically, the strategy makes sense. Methotrexate has long been used to dampen immune activation and can complement biologic or targeted therapy by reducing inflammatory signaling across parallel pathways. In some patients, combination treatment may help maintain response durability and lower the likelihood that inflammation rebounds when one mechanism is suppressed but others remain active. The study does not measure mechanisms directly, but the clinical trajectory is compatible with that pharmacologic logic.
Guideline-Concordant Practice Remained the Dominant Pattern
The central conclusion is straightforward: clinicians largely followed current guideline-based practice by keeping methotrexate on board when initiating b/tsDMARD therapy for rheumatoid arthritis. The STRATEGE2 cohort does not present this as an experimental strategy or a contested approach. It documents what rheumatology teams already do when faced with persistent disease despite methotrexate monotherapy: they commonly continue the conventional agent and build on it rather than replacing it outright.
That approach also helps explain why subcutaneous methotrexate remained so common at baseline and why the same dose and route were preserved in many patients at 12 months. Once a patient has tolerated methotrexate and is deriving some benefit, stopping it at the point of biologic or targeted initiation may not be the default choice. The combination strategy is simpler to justify when the disease is active, the safety profile is acceptable, and the treatment goal is remission rather than partial control.
What This Cohort Adds to Everyday Rheumatology Decisions
STRATEGE2 is non-interventional, so it reflects practice rather than imposing a treatment algorithm. That makes it especially useful for understanding how rheumatologists manage the transition from conventional to advanced therapy in real life. The cohort was not large enough to settle every question about which patients need methotrexate continuation and which can safely discontinue it, but it does show that continuation is the prevailing standard across a multicenter prospective setting.
The durability of remission at 2 years also argues against the idea that methotrexate must be dropped when a biologic or targeted drug begins. For many patients, the two therapies work as partners rather than competitors. Still, the reasons for stopping methotrexate—especially patient choice and adverse events—signal that the decision remains individualized and can shift as treatment burden accumulates over time.
The trial registration identifies STRATEGE2 as a therapeutic strategy study spanning bDMARDs and tsDMARDs in rheumatoid arthritis and psoriatic arthritis, but the data presented here center on the rheumatoid arthritis cohort and its methotrexate continuation pattern. What remains unresolved is not whether combination therapy is common, but which clinical subgroups are most likely to keep methotrexate long term without sacrificing tolerability or adherence.