RINVOQ® (upadacitinib) Efficacy for Giant Cell Arteritis

GCA patients on a 26-wk CS taper achieved sustained remission from Week 12 through 52 (primary endpoint). In patients who sustained remission from Week 28–52 with RINVOQ, remission rates were observed out to 2 years.^1-3

CS=corticosteroid; GCA=giant cell arteritis.

INDICATION

RINVOQ is indicated for the treatment of adults with giant cell arteritis (GCA).

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

NRI Data From SELECT-GCA^1,2

RINVOQ 15 mg + 26-wk CS taper (n=209), placebo + 52-wk CS taper (n=112)

Sustained Remission | PRIMARY ENDPOINT

46% RINVOQ vs 29% placebo + 52-wk CS taper from Week 12 through 52*

*P=0.002.

SELECT-GCA^1,2: 52-wk, randomized, double-blind, placebo‍-‍controlled study of 428 adult patients age 50+ with GCA. Patients were randomized to receive RINVOQ 15 mg + 26-wk CS taper or placebo + 52-wk CS taper.

Sustained remission: Absence of GCA signs and symptoms from Week 12 through 52 and adherence to the protocol-defined CS-taper regimen.

Please see Important Safety Information, including BOXED WARNING on Serious Infections, Mortality, Malignancies, Major Adverse Cardiovascular Events, and Thrombosis, below.

Learn more about these and the full Important Safety Information below

Rapid and Substantial Steroid Reduction

40% less cumulative steroid exposure with most patients off steroids in half the time
on RINVOQ 15 mg + 26-wk CS taper vs placebo + 52-wk CS taper^2,4

SELECT-GCA Period 1 (Week 0–52)

ALL DATA ARE AS OBSERVED CASES

Median Cumulative CS Exposure

At 52 weeks, patients on RINVOQ 15 mg + 26-wk CS taper were exposed to a 1615 mg median cumulative CS dose vs 2882 mg in patients on placebo + 52-wk CS taper.

At Week 52, a substantially lower cumulative CS dose was observed in the RINVOQ 15 mg + 26‍-‍wk CS-taper arm.

The cumulative CS exposure includes all CS use during the 52 weeks of the trial. This includes the CS dose per protocol and above protocol.

SEE HOW MANY PATIENTS WERE EXPOSED TO CS FROM WEEK 52–104

DATA LIMITATIONS: Data not labeled as ranked secondary endpoints were prespecified nonranked endpoints not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

Steroid-free Complete Remission Achieved at 1 Year, With Rates Observed
Out to 2 Years

WEEK 0–52

WEEK 52–104

Steroid-free remission achieved in a significantly higher proportion of patients at 1 year^2,4

SELECT-GCA Period 1

NRI-MI

Complete Remission

Defined as achieving all of the following:

NO GCA signs and symptoms
NO additional steroids above protocol-defined CS-taper regimen
Normalization of ESR and hsCRP

Steroid-free remission rates observed out to 2 years^6,7

SELECT-GCA Period 2

Patients with sustained remission on RINVOQ from Week 28–52

NRI-MI

Complete Remission

Defined as achieving all of the following:

NO GCA signs and symptoms
NO steroid use
Normalization of ESR and hsCRP

DATA LIMITATIONS: Data were prespecified nonranked endpoints not controlled for multiplicity; therefore, treatment differences could represent chance findings. No conclusions regarding these comparisons can be made.

Safety Considerations

Serious Infections: RINVOQ-treated patients are at increased risk of serious bacterial (including tuberculosis [TB]), fungal, viral, and opportunistic infections leading to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids.

Mortality: A higher rate of all-cause mortality, including sudden cardiovascular (CV) death, was observed with a Janus kinase inhibitor (JAKi) in a study comparing another JAKi with tumor necrosis factor (TNF) blockers in rheumatoid arthritis (RA) patients ≥50 years with ≥1 CV risk factor.

Malignancies: Malignancies have occurred in RINVOQ-treated patients. A higher rate of lymphomas and lung cancer (in current or past smokers) was observed with another JAKi when compared with TNF blockers in RA patients.

Major Adverse Cardiovascular Events: A higher rate of CV death, myocardial infarction, and stroke was observed with a JAKi in a study comparing another JAKi with TNF blockers in RA patients ≥50 years with ≥1 CV risk factor. History of smoking increases risk.

Thromboses: Deep venous thrombosis, pulmonary embolism, and arterial thrombosis have occurred in patients treated for inflammatory conditions with JAK inhibitors, including RINVOQ. A higher rate of thrombosis was observed with another JAKi when compared with TNF blockers in RA patients.

Hypersensitivity: RINVOQ is contraindicated in patients with hypersensitivity to RINVOQ or its excipients.

Other Serious Adverse Reactions: Hypersensitivity Reactions, Gastrointestinal Perforations, Laboratory Abnormalities, and Embryo-Fetal Toxicity.

Learn more about these and the full Important Safety Information below

Safety Considerations

Consider the Benefits and Risks for the Individual Patient Prior to Initiating Therapy with RINVOQ

Cumulative Exposure to Additional Rescue Steroid at Week 52

SELECT-GCA

Post hoc Analysis

This data is derived from a post hoc analysis of the cumulative CS exposure through Week 52.

RESCUE STEROIDS: Patients unable to adhere to the CS-taper protocol due to disease flare received open-label CS rescue therapy at the investigator’s discretion. Patients who required rescue CS were no longer in remission.

DATA LIMITATIONS: Post hoc subgroup analysis data not controlled for multiplicity; therefore, treatment difference could represent chance findings. No conclusions regarding these comparisons can be made.

Interested in the safety data for RINVOQ?

See RINVOQ’s safety data across clinical trials

See Safety Profile

	PERIOD 1 (Week 0–52)	PERIOD 2 (Week 52–104)
GCA signs and symptoms	Absent	Absent
Corticosteroid status	Adherence to the protocol-defined CS-taper regimen (RINVOQ: 26-wk taper; placebo: 52-wk taper)	CS-free
ESR	≤30 mm/hr	≤30 mm/hr
hsCRP	<1 mg/dL	<1 mg/dL

Subject Disposition	Placebo + 52-wk CS Taper N=112 n (%)	RINVOQ 15 mg + 26-wk CS Taper N=209 n (%)
Randomized and dosed	112 (100)	209 (100)
Completed Study Drug in Period 1	71 (63.4)	155 (74.2)
Prematurely Discontinued Study Drug in Period 1 (Primary Reasons)	41 (36.6)	54 (25.8)
Adverse Event	23 (20.5)	32 (15.3)
Withdrew Consent	3 (2.7)	8 (3.8)
Lost to Follow-Up	0	0
Lack of Efficacy	8 (7.1)	7 (3.3)
COVID-19 Infection	0	0
COVID-19 Logistical Restrictions	1 (0.9)	0
Other	6 (5.4)	7 (3.3)

Baseline Characteristics and Demographics^1-3	Placebo + 52-wk CS Taper N=112	RINVOQ 15 mg + 26-wk CS Taper N=209	Stopped RINVOQ 15 mg and Switched to Placebo^† N=35	Continued RINVOQ 15 mg^† N=68
	PERIOD 1 (WEEK 0–52)		PERIOD 2 (WEEK 52–104)*
Female, n (%)	77 (68.8)	156 (74.6)	27 (77.1)	51 (75.0)
Age (years), mean (SD)	71.6 (7.3)	70.8 (7.3)	69.9 (6.7)	71.3 (8.2)
Age group (years), n (%)
<65	17 (15.2)	42 (20.1)	9 (25.7)	12 (17.6)
≥65 to <75	59 (52.7)	102 (48.8)	16 (45.7)	34 (50)
≥75	36 (32.1)	65 (31.1)	10 (28.6)	22 (32.4)
BMI (kg/m²), mean (SD)	25.8 (4.3)	25.3 (4.6)	24 (3.7)	25 (4.2)
Prior use of IL-6 inhibitor, n (%)	7 (6.2)	9 (4.3)	4 (11.4)	2 (2.9)
Baseline CS dose (mg), mean (SD)	34.6 (11.9)	34.6 (12.7)	32.3 (12.4)	33.1 (12.4)
New onset of GCA, n (%)	76 (67.9)	148 (70.8)	26 (74.3)	49 (72.1)
Relapsing GCA, n (%)	36 (32.1)	61 (29.2)	9 (25.7)	19 (27.9)
Disease duration since diagnosis (days), mean (SD)
New-onset disease	38.2 (14.8)	39.5 (28.1)	39.9 (13.7)	46.0 (45.5)
Relapsing disease	665.7 (816.3)	664.9 (687.5)	931.6 (769.7)	757.4 (770.6)
ESR (mm/hr), mean (SD)	21.7 (25.5)	19.5 (17.5)	15.9 (12.8)	20.9 (17.9)
hsCRP (mg/dL), median (min, max)	0.23 (0.02, 5.83)	0.24 (0.02, 10.10)	0.27 (0.02, 10.0)	0.24 (0.02, 3.5)
History of PMR	69 (61.6)	109 (52.2)	19 (54.3)	35 (51.5)
History of TAB	44 (39.3)	86 (41.1)	17 (48.6)	27 (39.7)
Evidence of LVV	81 (73.0)	159 (76.1)	26 (74.3)	52 (76.5)
Ischemia-related vision loss	22 (19.6)	20 (9.6)	5 (14.3)	2 (2.9)

MEAN (SD) or n (%)	PBO + 52-wk CS Taper (n=112)	RINVOQ 15 mg + 26-wk CS Taper (n=209)	Stopped RINVOQ 15 mg and Switched to PBO^§(n=35)	Continued RINVOQ 15 mg^§(n=68)
	PERIOD 1 (WEEK 0–52)		PERIOD 2 (WEEK 52–104)^‡
Female, n (%)	77 (68.8)	156 (74.6)	27 (77.1)	51 (75.0)
Age (years), mean (SD)	71.6 (7.3)	70.8 (7.3)	69.9 (6.7)	71.3 (8.2)
Age group (years), n (%)
<65	17 (15.2)	42 (20.1)	9 (25.7)	12 (17.6)
≥65 to <75	59 (52.7)	102 (48.8)	16 (45.7)	34 (50)
≥75	36 (32.1)	65 (31.1)	10 (28.6)	22 (32.4)
BMI (kg/m²), mean (SD)	25.8 (4.3)	25.3 (4.6)	24 (3.7)	25 (4.2)
Prior use of IL-6 inhibitor, n (%)	7 (6.2)	9 (4.3)	4 (11.4)	2 (2.9)
Baseline CS dose (mg), mean (SD)	34.6 (11.9)	34.6 (12.7)	32.3 (12.4)	33.1 (12.4)
New onset of GCA, n (%)	76 (67.9)	148 (70.8)	26 (74.3)	49 (72.1)
Relapsing GCA, n (%)	36 (32.1)	61 (29.2)	9 (25.7)	19 (27.9)
Disease duration since diagnosis (days), mean (SD)
New-onset disease	38.2 (14.8)	39.5 (28.1)	39.9 (13.7)	46.0 (45.5)
Relapsing disease	665.7 (816.3)	664.9 (687.5)	931.6 (769.7)	757.4 (770.6)
ESR (mm/hr), mean (SD)	21.7 (25.5)	19.5 (17.5)	15.9 (12.8)	20.9 (17.9)
hsCRP (mg/dL), median (min, max)	0.23 (0.02, 5.83)	0.24 (0.02, 10.10)	0.27 (0.02, 10.0)	0.24 (0.02, 3.5)
History of PMR, n (%)	69 (61.6)	109 (52.2)	19 (54.3)	35 (51.5)
History of TAB, n (%)	44 (39.3)	86 (41.1)	17 (48.6)	27 (39.7)
Evidence of LVV, n (%)	81 (73.0)	159 (76.1)	26 (74.3)	52 (76.5)
Ischemia-related vision loss, n (%)	22 (19.6)	20 (9.6)	5 (14.3)	2 (2.9)

	Blinded 52-wk CS* Taper (mg)
Baseline	20	30	40	50	60
Week 1	17	25	35	40	50
Week 2	17	20	30	35	40
Week 3	15	17	25	30	35
Week 4	15	17	20	25	30
Week 5	12	15	17	20	25
Week 6	10	15	17	17	20
Week 7	10	12	15	17	17
Week 8	10	10	15	16	17
Week 9	10	10	12	15	15
Week 10	9	10	10	12	15
Week 11	9	10	10	10	12
Week 12	9	9	10	10	10
Week 13	9	9	10	10	10
Week 14	8	9	9	10	10
Week 15+	Taper 1 mg every 4 weeks until 0 mg at Week 46	Taper 1 mg every 4 weeks until 0 mg at Week 48	Taper 1 mg every 4 weeks until 0 mg at Week 50	Taper 1 mg every 4 weeks until 0 mg at Week 51	Taper 1 mg every 4 weeks until 0 mg at Week 52

DURABLE REMISSION WITH RAPID STEROID REDUCTION

Rapid and Substantial Steroid Reduction

Steroid-free Complete Remission Achieved at 1 Year, With Rates Observed Out to 2 Years

Safety Considerations

Safety Considerations

Cumulative Exposure to Additional Rescue Steroid at Week 52

Interested in the safety data for RINVOQ?

IMPORTANT SAFETY INFORMATION & INDICATIONS1

INDICATION1

IMPORTANT SAFETY INFORMATION FOR RINVOQ/RINVOQ LQ (upadacitinib)

SERIOUS INFECTIONS

MORTALITY

MALIGNANCIES

MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)

THROMBOSIS

HYPERSENSITIVITY

GASTROINTESTINAL PERFORATIONS

LABORATORY ABNORMALITIES

EMBRYO-FETAL TOXICITY

VACCINATION

MEDICATION RESIDUE IN STOOL

LACTATION

HEPATIC IMPAIRMENT

ADVERSE REACTIONS

IMPORTANT SAFETY INFORMATION & INDICATIONS1

INDICATIONS1

IMPORTANT SAFETY INFORMATION FOR RINVOQ/RINVOQ LQ (upadacitinib)

SERIOUS INFECTIONS

MORTALITY

MALIGNANCIES

MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE)

THROMBOSIS

HYPERSENSITIVITY

GASTROINTESTINAL PERFORATIONS

LABORATORY ABNORMALITIES

EMBRYO-FETAL TOXICITY

VACCINATION

MEDICATION RESIDUE IN STOOL

LACTATION

HEPATIC IMPAIRMENT

ADVERSE REACTIONS

DURABLE REMISSION
WITH RAPID STEROID REDUCTION

Steroid-free Complete Remission Achieved at 1 Year, With Rates Observed
Out to 2 Years

IMPORTANT SAFETY INFORMATION & INDICATIONS¹

INDICATION¹

IMPORTANT SAFETY INFORMATION & INDICATIONS¹

INDICATIONS¹