SELECT-GCA:
A Phase 3 Trial of Upadacitinib in Patients With GCA
- 15-minute listen
Podcast
- Dr. Andrea Rubbert-Roth • May 2025
The expert
Andrea Rubbert-Roth, MD
Senior Physician,
Division of Rheumatology,
Kantonsspital St. Gallen,
St. Gallen, Switzerland
Study design
Target population:
- People ≥50 years old with new-onset or relapsing GCA who had received prior GCA treatment with ≥40 mg prednisone QD (or equivalent) before baseline and were on prednisone ≥20 mg QD (or equivalent) at baseline
- Excluded patients with prior JAK inhibitor exposure, inadequate response to IL-6is, exposure to IL-6is within 4 weeks of baseline, and chronic use of systemic GCs
*R1=remission at Week 52 with continuous achievement of remission for ≥24 weeks prior.
†R2=remission at Week 52 and continuous achievement of remission for <24 weeks prior.
*Most of whom were from Japan (placebo group, n=5; UPA 15 mg + 26-week GC taper group, n=10).
†Patients previously treated with an IL-6i who experienced disease flare during treatment were excluded from study entry.
UPA 15 mg + 26-week GC taper met its primary endpoint and 9 of the 11 ranked secondary endpoints
Sustained remission is defined as:
- Absence of GCA signs and symptoms from Week 12–52
- Adherence to the protocol-defined GC taper regimen
Sustained complete remission is defined as:
- Sustained remission
- Normalization of ESR (to <30 mm/hr*) and hsCRP (to <1 mg/dL, without elevation to ≥1 mg/dL [on 2 consecutive visits]) from Week 12–52
Ranked secondary endpoint: Median cumulative GC* exposure through 52 weeks
Cumulative GC* exposure was lower in patients receiving UPA 15 mg + 26-week GC taper vs PBO + 52-week GC taper through 52 weeks
*In prednisone/prednisolone equivalents.
Safety
Adverse reaction rates observed in clinical trials may not fully characterize the risks of UPA. Certain adverse events may require longer observation periods and longer-term patient exposure to ascertain risk.
The safety profile observed in patients with GCA was generally consistent with the known safety profile for upadacitinib. Refer to the upadacitinib Important Safety Considerations regarding risk of serious infections, mortality, malignancies, MACE, and thromboses.
Abbreviations
CI: confidence interval; CRP: C-reactive protein; DB: double-blind; E: event; ESR: erythrocyte sedimentation rate; GC: glucocorticoid; GCA: giant cell arteritis; GI: gastrointestinal; hr: hour; IL-6: interleukin-6; IL-6i: interleukin-6 inhibitor; JAK: Janus kinase; MACE: major adverse cardiovascular event; NMSC: nonmelanoma skin cancer; PBO: placebo; PMR: polymyalgia rheumatica; PY: patient-years; QD: once a day; SD: standard deviation; TEAE: treatment-emergent adverse event; UPA: upadacitinib; VTE: venous thromboembolism; wk: week.
Upadacitinib INDICATIONS
Upadacitinib is a Janus kinase (JAK) inhibitor indicated for the treatment of:
Adults with giant cell arteritis (GCA).
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.
Common Adverse Reactions in GCA: The most common adverse reactions (≥5%) are upper respiratory tract infections, headache, fatigue, peripheral edema, cough, anemia, rash, herpes zoster, and nausea.
Review accompanying upadacitinib full Prescribing Information for additional information, visit www.rxabbvie.com or contact AbbVie Medical Information at 1-800-633-9110.
Reference:
Blockmans D et al. N Engl J Med. Published online April 2, 2025. doi: 10.1056/NEJMoa2413449.
