Aug2026 - RN15

UPA After TNFi Failure in RA: SELECT-SWITCH at Week 12

15-minute listen

Rheumatologists Dr. Christina Charles-Schoeman and Dr.
Manish Jain return for a new episode!

- Recent data from SELECT-SWITCH, including a post hoc analysis presented at EULAR 2026
- Insights on RA treatment decisions after TNFi failure
- Patient case discussion

Podcast: Recent findings, new insights

Making the SWITCH in RA

Dr. Christina Charles-Schoeman & Dr. Manish Jain • August 2026

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The experts

Christina Charles-Schoeman, MD, MS

Professor of Medicine
Chief of the Division of Rheumatology
UCLA Health
Los Angeles, CA

Manish Jain, MD

Attending Physician
Ravenswood Rheumatology
Chicago, IL

Disease control is the goal for every patient

Uncontrolled disease is associated with higher long-term comorbidity risk

CV Disease^1–3

Malignancy^1–4

Serious Infections^5,6

Longer duration of disease is associated with a lower likelihood of remission7

Therapy in RA should be individualized to patients and their treatment goals

Listen to Episode 1 to review considerations for treatment decisions in RA

Despite being standard first-line advanced therapy, many patients fail their first TNFi^8-11

Types of TNFi nonresponse¹²

What guides your treatment decisions after TNFi failure?

Treatment Guidelines

ACR: Conditionally recommend MoA switch over 2nd TNFi13

EULAR: Recommend either MoA switch or 2nd TNFi14

While guidelines were developed based on real-world evidence, data from RCTs directly comparing options was limited^13-18

Real-world treatment decisions

Review a hypothetical patient case similar to what was discussed in the podcast

Patient Case: The Drummer

Key case details:

- 62 years old
- Debilitating impact of RA on his life and profession
- Symptoms did not improve within 3 months of starting TNFi therapy (primary nonresponder)

The Decision: Use a second TNFi or switch to a JAKi?

Considerations for his next treatment

Long-term risks
with uncontrolled
disease

Treatment
benefit vs risk

Patient preferences 

“We then have to take all that information about the patient's treatment history, their comorbidities, lifestyle, and then come to a shared decision” – Dr. Jain

Within weeks of starting a JAKi, his symptoms noticeably improved

“It's remarkable how their life just changes tremendously when you hit a mechanism of action that works” – Dr. Charles-Schoeman

What is the latest data to support this clinical decision?

SELECT-SWITCH

SELECT-SWITCH is the first RCT to assess switching to upadacitinib (UPA) vs adalimumab (ADA) after first TNFi failure

This trial directly addresses optimal treatment sequencing in a head-to-head trial

SELECT-SWITCH is a randomized, double-blind study in adults with moderate-to-severe RA who failed one TNFi (non-ADA)^19,20

^aAt W12, W24, or W36 (after W12 assessments have been performed), patients who do not achieve ≥20% improvement in both TJC and SJC compared with baseline are rescued with optimizing (initiate or increase) background RA medications: NSAIDs, corticosteroids, acetaminophen, or adding or increasing doses in up to 2 csDMARDs (except the combination of MTX and leflunomide).  bAt W24 or W36, patients who do not achieve ≥20% improvement in both TJC and SJC, despite optimization of background RA therapies at the previous visit, are discontinued from study drug and treated according to standard of care at the discretion of the clinician.

Key baseline demographics and clinical characteristics^19,20

^aClassifications for sex and gender were defined as male or female per the protocol.
^bADA n=246, UPA n=244 , total N=490.
^cADA n=245, UPA n=245, total N=490.
^dADA n=236, UPA n=235, total N=471.
^eCV risk were defined as prior history of a CV event, hypertension, diabetes mellitus, current or former smoker, elevated LDL-C (≥3.36 mmol/L), and lowered HDL-C (<1.034 mmol/L).

In patients with one TNFi failure,
UPA15 + MTX was superior to ADA + MTX in DAS28-CRP LDA and remission at Week 12¹⁹

Achievement of DAS28-CRP LDA at W1219

(DAS28-CRP ≤3.2; primary endpoint)

*nominal P<0.05.

Achievement of DAS28-CRP remissiona at W1219

(DAS28-CRP <2.6; ranked secondary endpoint)

aRemission does not mean drug-free remission or complete absence of disease activity.

UPA15 + MTX achieved higher rates of CDAI LDA vs ADA + MTX at Week 12¹⁹

Achievement of CDAI LDA at W12¹⁹

(CDAI ≤10; additional endpoint)

****nominal P<0.0001.

Achievement of CDAI remissiona at W12¹⁹

(CDAI ≤2.8; additional endpoint)

^aRemission does not mean drug-free remission or complete absence of disease activity.

SELECT-SWITCH Manuscript: Primary Analysis Results

Review the April 2026 publication from the Annals of the Rheumatic Diseases, which includes additional efficacy results and patient-reported outcomes from the primary analysis of SELECT-SWITCH

In a post hoc analysis, UPA15 + MTX achieved numerically higher rates of LDA and remission in both primary and secondary nonresponders²¹

Achievement of DAS28-CRP LDA and remission^a at W12 in primary and secondary nonresponders²¹

^aRemission does not mean drug-free remission or complete absence of disease activity.

Achievement of DAS28-CRP LDA and remission^a at W12 in primary and secondary nonresponders²¹

^aRemission does not mean drug-free remission or complete absence of disease activity.

Poster presented at EULAR 2026: Post hoc analysis of primary and secondary nonresponders

See the full results of the SELECT-SWITCH post hoc analysis presented at EULAR 2026

Safety through Week 12¹⁹

Laboratory abnormalities: Patients with laboratory-related treatment-emergent AEs for ADA and UPA, respectively, n (%): anemia (1 [0.4%], 4 [1.6%]), neutropenia (3 [1.2%], 1 [0.4%]), lymphopenia (1 [0.4%], 2 [0.8%]), and hepatic disorders (4 [1.6%], 7 [2.9%]).

UPA requires laboratory monitoring for neutropenia, lymphopenia, anemia, increased lipids, and AST/ALT elevations, whereas ADA does not.

Common Adverse Reactions in RA: The most common adverse reactions (≥1%) were upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, and headache.

Adverse reaction rates observed in clinical trials and long-term extension studies may not predict rates observed in clinical practice.

^aDefined as an AE with an onset date on or after the first dose of study drug in a controlled short-term period, or up to 30 days after the last dose of UPA and up to 70 days for ADA, if patients discontinued prematurely before W12 visit.22
^bOne patient randomized to the ADA arm did not receive active treatment, only oral placebo, and was therefore excluded from the safety analysis set.
^cNo ophthalmic herpes zoster or herpes zoster with liver or CNS involvement were reported.
^dMACE is defined as CV death, nonfatal MI, and nonfatal stroke.22
^eVTE includes DVT and PE.22

Consider how SELECT-SWITCH may support your treatment decisions with patients with RA who failed initial TNFi therapy

Additionally, consider the data across the UPA RA clinical program to support these decisions

UPA15 in patients with moderately to severely active RA:

- Safety data through ~9.5 years²³
- Met all primary endpoints across seven Phase 3 clinical trials^19,24-29

Long-term UPA safety has been assessed through up to 9.5 years in the SELECT RA clinical program^a,23

^aSafety data for ADA reported from the active comparator arm of SELECT-COMPARE and data for UPA15 reported from the 6 SELECT RA clinical trials with long-term data reported (does not include SELECT–SWITCH).
^bDefined as an AE with an onset date on or after the first dose of study drug and up to 30 days after the last dose of UPA and 70 days for ADA, if subjects discontinued prematurely from the study.
^cStudy size-adjusted number of patients with ≥1 event per 100 PYs.
^dn/100 PYs.
^eMACE is defined as CV death, nonfatal MI, and nonfatal stroke.
^fVTE includes DVT and PE.

UPA achieved higher rates of LDA and remission versus ADA and abatacept (ABA) across three head-to-head clinical trials (COMPARE, SWITCH, and CHOICE)19,24,25

Achievement of LDA at Week 1219,24,25

(DAS28-CRP ≤3.2)

***nominal P≤0.001

SELECT-COMPARE: A 48-week study of 1629 adults who had an inadequate response to MTX. Patients on background MTX received UPA15 (n=651), placebo (n=651), or ADA 40 mg EOW (n=327). UPA met the primary endpoint: 71% of patients in the UPA15 + MTX group achieved ACR20 at W12 vs 36% in the PBO group (P≤0.001).24

SELECT-CHOICE: A 24-week study of 612 adults who have had an inadequate response to bDMARDs. Patients on stable csDMARDs received UPA15 or weight-based ABA IV. UPA met the primary endpoint: Mean change in DAS28-CRP was −2.52 in the UPA15 + csDMARD group vs −2.00 in the ABA + csDMARD group (P<0.001).25

Achievement of remissiona at Week 12^19,24,25

(DAS28-CRP <2.6)

***nominal P≤0.001

^aRemission does not mean drug-free remission or complete absence of disease activity.

UPADACITINIB INDICATIONS

Upadacitinib is a Janus kinase (JAK) inhibitor indicated for the treatment of:

Adults with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.

Limitations of Use: Upadacitinib is not recommended for use in combination with other JAK inhibitors, biologic disease-modifying antirheumatic drugs (bDMARDs), or with potent immunosuppressants such as azathioprine and cyclosporine.

UPADACITINIB IMPORTANT SAFETY CONSIDERATIONS AND BOXED WARNING

Serious Infections: Patients treated with upadacitinib are at increased risk for developing serious infections that may lead to hospitalization or death. These infections include tuberculosis (TB), invasive fungal, bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids. Test for latent TB before and during therapy; treat latent TB prior to use. Consider the risks and benefits prior to initiating therapy in patients with chronic or recurrent infection. If a serious infection develops, interrupt upadacitinib until the infection is controlled.

Mortality: In a postmarketing safety study in RA patients ≥ 50 years of age with at least one cardiovascular (CV) risk factor comparing another JAK inhibitor to TNF blockers, a higher rate of all-cause mortality, including sudden CV death, was observed with the JAK inhibitor.

Malignancies: Malignancies have been observed in upadacitinib treated patients. In RA patients treated with another JAK inhibitor, a higher rate of lymphomas and lung cancers was observed when compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with upadacitinib, particularly in patients with a known malignancy (other than a successfully treated non-melanoma skin cancer [ NMSC ]), patients who develop a malignancy when on treatment, and patients who are current or past smokers. NMSCs have been reported in patients treated with upadacitinib. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. Advise patients to limit sunlight exposure by wearing protective clothing and using sunscreen.

Major Adverse Cardiovascular Events (MACE): In RA patients who were ≥ 50 years of age with at least one CV risk factor treated with another JAK inhibitor, a higher rate of MACE (CV death, myocardial infarction, and stroke) was observed compared with TNF blockers. Patients who are current or past smokers are at additional increased risk. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with upadacitinib. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. Discontinue upadacitinib in patients that have experienced a myocardial infarction or stroke.

Thrombosis: Thromboses, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have occurred in patients treated with JAK inhibitors, including upadacitinib. Many of these adverse events were serious and some resulted in death. In RA patients who were ≥ 50 years of age with at least one CV risk factor treated with another JAK inhibitor, a higher rate of thrombosis was observed when compared with TNF blockers. Avoid upadacitinib in patients at risk. Patients with symptoms of thrombosis should discontinue upadacitinib and be promptly evaluated.

Hypersensitivity Reactions: Upadacitinib is contraindicated in patients with known hypersensitivity to upadacitinib or any of its excipients. Serious hypersensitivity reactions such as anaphylaxis and angioedema were reported in patients receiving upadacitinib in clinical trials. If a clinically significant hypersensitivity reaction occurs, discontinue upadacitinib and institute appropriate therapy.

Other Serious Adverse Reactions: Patients treated with upadacitinib also may be at risk for other serious adverse reactions, including gastrointestinal perforations, neutropenia, lymphopenia, anemia, lipid elevations, liver enzyme elevations, and embryo-fetal toxicity. If upadacitinib exposure occurs during pregnancy, please report the pregnancy to the surveillance program by calling 1-800-633-9110.

Vaccinations: Avoid use of live vaccines during, or immediately prior to, upadacitinib therapy. Prior to initiating upadacitinib, it is recommended that patients be brought up to date with all immunizations, including prophylactic varicella zoster or herpes zoster vaccinations, in agreement with current immunization guidelines.

Medication Residue in Stool: Reports of medication residue in stool or ostomy output have occurred in patients taking upadacitinib extended-release tablet. Most reports described patients with shortened gastrointestinal transit times. Instruct patients to contact their healthcare provider if medication residue is observed repeatedly.

Review accompanying upadacitinib full Prescribing Information for additional information, visit www.rxabbvie.com or contact AbbVie Medical Information at 1-800-633-9110.

ADALIMUMAB INDICATIONS

Adalimumab is a tumor necrosis factor (TNF) blocker indicated for the treatment of:

Rheumatoid Arthritis: reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA.

ADALIMUMAB IMPORTANT SAFETY CONSIDERATIONS AND BOXED WARNING

Serious infections

Patients treated with adalimumab are at an increased risk of developing serious infections that may lead to hospitalization or death. These infections include active tuberculosis (TB), reactivation of latent TB, invasive fungal infections, and bacterial, viral, and other infections due to opportunistic pathogens. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Malignancies

Lymphoma, including a rare type of T-cell lymphoma, and other malignancies, some fatal, have been reported in patients treated with TNF blockers, including adalimumab. 

Other Serious Adverse Reactions

Patients treated with adalimumab also may be at risk for other serious adverse reactions, including anaphylaxis, hepatitis B virus reactivation, demyelinating disease, cytopenias, pancytopenia, heart failure, a lupus-like syndrome, and autoimmune hepatitis. Avoid live vaccines in patients taking adalimumab.

Common Adverse Reactions

The most common adverse reactions in adalimumab clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.

Review accompanying adalimumab full Prescribing Information for additional information, visit www.rxabbvie.com or contact AbbVie Medical Information at 1-800-633-9110.

ABATACEPT INDICATIONS

Rheumatoid Arthritis

Abatacept is indicated for the treatment of adults with moderately to severely active RA.

Limitations of Use: The concomitant use of abatacept with other potent immunosuppressants (e.g., biologic DMARDs, JAK inhibitors) is not recommended.

ABATACEPT IMPORTANT SAFETY CONSIDERATIONS

BOXED WARNING: None

CONTRAINDICATIONS: None

Malignancies

WARNINGS AND PRECAUTIONS

Infections: Concomitant use with a TNF blocker can increase the risk of infections and serious infections. Serious infections have been reported. Patients with a history of recurrent infections or underlying conditions predisposing to infections may experience more infections. Discontinue if a serious infection develops. Screen for latent TB infection prior to initiating therapy. Patients testing positive should be treated prior to initiating abatacept.

Hypersensitivity and anaphylaxis have occurred.

Screen for viral hepatitis prior to initiating abatacept.

The most common adverse reactions in adalimumab clinical trials (>10%) were: infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.

Vaccinations: Update vaccinations prior to initiating abatacept. Live vaccines should not be given concurrently or within 3 months of discontinuation. Abatacept may blunt the effectiveness of some immunizations.

Chronic Obstructive Pulmonary Disease: COPD patients may develop more frequent respiratory adverse events.

Common Adverse Reactions: The most common adverse reactions (≥10%) are headache, upper respiratory tract infections, nasopharyngitis, and nausea.

For additional information, please refer to abatacept Prescribing Information.

Want to learn more about how to assess benefit-risk when considering a switch to UPA?

Previously on RheumNow: Decision-making in uncontrolled RA

Listen to Dr. Jeffrey Curtis and Dr. Kevin Winthrop discuss how they talk to their patients about the risks of uncontrolled RA and the efficacy and safety of upadacitinib

Previously on RheumNow: Decision-making in uncontrolled RA

Listen to Dr. Jeffrey Curtis and Dr. Kevin Winthrop discuss how they talk to their patients about the risks of uncontrolled RA and the efficacy and safety of upadacitinib

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Making the SWITCH in RA

Key baseline demographics and clinical characteristics19,20​

Key baseline demographics and clinical characteristics^19,20