RINVOQ

Upadacitinib is an oral

Janus kinase (JAK)1-selective inhibitor and a disease-modifying antirheumatic drug (DMARD) used in the treatment of rheumatoid arthritis to slow down disease progression.

Rheumatoid arthritis is a chronic autoimmune inflammatory disease affecting the peripheral joints.

It is characterized by synovial inflammation and hyperplasia, autoantibody production, cartilage damage and bone destruction, leading to co-morbidities.

Despite a variety of therapeutic agents available for treatment, up to 40% of the patients do not respond to current therapies, including biological therapies.

The etiology of the disease is mostly unknown; however, the role of JAK as a driver of immune-mediated conditions was discovered, leading to the use of JAK as therapeutic targets for rheumatoid arthritis.

To reduce dose-related toxicity (as seen with some pan-JAK inhibitors) without significantly affecting efficacy, more selective JAK1 inhibitors, upadacitinib and filgotinib, were developed.

The FDA approved upadacitinib in

August and it is used for the treatment of active rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, and ankylosing spondylitis.

In December 2019, it was additionally approved by the European Commission and Health Canada. 10, 15 Upadacitinib is marketed under the brand name RINVOQ for oral administration. 9.

More recently, it has also been approved for the treatment of giant cell arteritis in adults and active polyarticular juvenile idiopathic arthritis in patients aged 2 years and older.

Upadacitinib is indicated for the treatment of moderately to severely active rheumatoid arthritis or active psoriatic arthritis in adult patients who have had an inadequate response or intolerance to one or more disease-modifying anti-rheumatic drugs (DMARDs), such as TNF blockers. 9, 14 In Europe, upadacitinib may be used as monotherapy or in combination with methotrexate for rheumatoid or psoriatic arthritis.

Upadacitinib is indicated for use in patients 12 years of age and older with refractory, moderate-to-severe atopic dermatitis whose disease is inadequately controlled with other systemic therapies or when other therapies are inadvisable. 9, 14 Upadacitinib is indicated for the treatment of active ankylosing spondylitis or radiographic axial spondyloarthritis in adult patients who have an inadequate response to conventional therapy. 9, 14 It is also indicated to treat non-radiographic axial spondyloarthritis with objective signs of inflammation in adults who have had an inadequate response or intolerance to TNF blocker therapy.

Upadacitinib is also indicated to treat moderately to severely active ulcerative colitis in adults who have had an inadequate response or intolerance to either conventional therapy or a biologic agent, 14 such as to one or more TNF blockers.

Upadacitinib is indicated to treat moderately to severely active Crohn's disease in adults who have had an inadequate response or intolerance to one or more TNF blockers. 17, 14 Upadacitinib is also indicated for the treatment of patients two years of age and older with active polyarticular juvenile idiopathic arthritis who have had an inadequate response or intolerance to one or more TNF blockers, and for the treatment of adults with giant cell arteritis. 9, 18 Combining upadacitinib with other JAK inhibitors, biologic DMARDs, or other potent immunosuppressive agents is not recommended.

Upadacitinib is a DMARD that works by inhibiting the Janus Kinases (JAKs), which are essential downstream cell signalling mediators of pro-inflammatory cytokines.

It is believed that these pro-inflammatory cytokines play a role in many autoimmune inflammatory conditions, such as rheumatoid arthritis.

In clinical trials, upadacitinib decreased the activity of pro-inflammatory interleukins, transiently increased the levels of lymphocytes, and insignificantly decreased the levels of immunoglobulins from the baseline.

Upadacitinib displays a dose-proportional pharmacokinetic profile over the therapeutic dose range.

Following oral administration, the median time to reach Cmax (Tmax) ranges from 2-4 hours.

The steady-state plasma concentrations of upadacitinib are reached within 4 days following multiple once-daily administrations, with minimal accumulation.

Food intake has no clinically relevant effect on the AUC, Cmax, and Cmin of upadacitinib from the extended-release formulation.

The volume of distribution of upadacitinib in a patient with rheumatoid arthritis and a body weight of 74 kg is estimated to be 224 L following oral administration of an extended-release formula.

In a pharmacokinetic study consisting of healthy volunteers receiving the extended-release formulation, the steady-state volume of distribution was 294 L.

Upadacitinib partitions similarly between plasma and blood cellular components with a blood to plasma ratio of 1.0.

Upadacitinib predominantly undergoes

CYP3A4-mediated metabolism; 9 however, upadacitinib is a nonsensitive substrate of CYP3A4.

It is also metabolized by

CYP2D6 to a lesser extent.

In a human radio-labelled study, about 79% of the total plasma radioactivity accounted for the parent drug, and about 13% of the total plasma radioactivity accounted for the main metabolite produced from mono-oxidation, followed by glucuronidation.

There are no known active metabolites of upadacitinib.

Following administration of a single radio-labelled dose from the immediate-release formulation, approximately 53% of the total dose was excreted in the feces where 38% of the excreted dose was an unchanged parent drug.

About 43% of the total dose was excreted in the urine, where 24% of that dose was in the unchanged parent drug form.

Approximately 34% of the total dose of upadacitinib dose was excreted as metabolites.

The mean terminal elimination half-life of upadacitinib ranged from 8-14 hours following administration of the extended-release formulation. 9, 11 In clinical trials, approximately 90% of upadacitinib in the systemic circulation was eliminated within 24 hours of dosing.

The apparent oral clearance of upadacitinib in healthy volunteers receiving the extended-release formulation was 53.7 L/h.

Improve decision support & research outcomes With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.

View sample adverse effects data in our new Data Library! See the data Improve decision support & research outcomes with our structured adverse effects data.

There is limited clinical information on the overdose from upacitinib: in clinical trials, once-daily administration of 60 mg in extended-release formulations were well tolerated.

In case of an overdose, it is recommended that the patient is monitored for signs and symptoms of adverse reactions and treated with appropriate symptomatic treatment.

The oral

LD in rats is 14500 mg/kg.

is contraindicated in patients with known hypersensitivity to upadacitinib or any of its excipients.

Known hypersensitivity to upadacitinib or any of the excipients in RINVOQ/RINVOQ LQ.

oral solution is not substitutable with RINVOQ extended-release tablets.

Changes between RINVOQ LQ oral solution and RINVOQ extended-release tablets should be made by the healthcare provider.

Prior to treatment update immunizations and consider evaluating for active and latent tuberculosis, viral hepatitis, hepatic function, and pregnancy status Avoid initiation or interrupt RINVOQ/RINVOQ LQ if absolute lymphocyte count is less than 500 cells/mm 3, absolute neutrophil count is less than 1000 cells/mm 3, or hemoglobin level is less than 8 g/dL.

Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis Adults: The recommended dosage of RINVOQ is 15 mg once daily.

Patients to less than 18 Years of Age Weighing at Least 10 kg: The recommended dosage is based on body weight Adults: The recommended dosage of RINVOQ is 15 mg once daily.

Patients 12 Years of Age and Older Weighing at Least 40 kg and Adults Less Than 65 Years of Age: Initiate treatment with RINVOQ 15 mg orally once daily.

If an adequate response is not achieved, consider increasing the dosage to 30 mg orally once daily.

Adults 65 Years of Age and Older: Recommended dosage of RINVOQ is 15 mg once daily.

Recommended dosage of RINVOQ is 15 mg once daily.

The recommended induction dosage of RINVOQ is 45 mg once daily for 8 weeks.

The recommended maintenance dosage of

RINVOQ is 15 mg once daily.

A maintenance dosage of 30 mg once daily may be considered for patients with refractory, severe, or extensive disease.

RINVOQ if adequate therapeutic response is not achieved with the 30 mg dosage.

Use the lowest effective dosage needed to maintain response.

Information for the recommended dosage in patients with renal or hepatic impairment and for dosage modification due to drug interactions.

Crohn’s D isease Adults: The recommended induction dosage of RINVOQ is 45 mg once daily for 12 weeks.

RINVOQ if an adequate therapeutic response is not achieved with the 30 mg dosage.

The recommended dosage is based on body weight Giant Cell Arteritis The recommended dosage of RINVOQ is 15 mg once daily in combination with a tapering course of corticosteroids.

RINVOQ 15 mg once daily can be used as monotherapy following discontinuation of corticosteroids 2.1 Recommended Evaluations and Immunizations Prior to Treatment Initiation Prior to RINVOQ/RINVOQ LQ treatment initiation, consider performing the following evaluations: Active and latent tuberculosis (TB) infection evaluation.

• If positive, treat for TB prior to RINVOQ/RINVOQ LQ use.

Viral hepatitis screening in accordance with clinical guidelines – RINVOQ/RINVOQ LQ initiation is not recommended in patients with active hepatitis B or hepatitis C.

A complete blood count – RINVOQ/RINVOQ LQ initiation is not recommended in patients with an absolute lymphocyte count less than 500 cells/mm 3, absolute neutrophil count less than 1000 cells/mm 3, or hemoglobin level less than 8 g/dL.

Baseline hepatic function

RINVOQ/RINVOQ LQ initiation is not recommended for patients with severe hepatic impairment (Child-Pugh C) .

Verify the pregnancy status of females of reproductive potential prior to starting treatment.

Update immunizations according to current immunization guidelines. 2.2 Important Administration Instructions RINVOQ LQ oral solution is not substitutable with RINVOQ extended-release tablets.

Changes between RINVOQ LQ oral solution and RINVOQ extended-release tablets should be made by the health care provider.

RINVOQ/RINVOQ LQ should be taken orally with or without food.

RINVOQ tablets should be swallowed whole.

RINVOQ tablets should not be split, crushed, or chewed.

LQ should be administered using the provided press-in bottle adapter and oral dosing syringe.

LQ is dosed twice daily. 2.3 Recommended Dosage in Rheumatoid Arthritis The recommended dosage of RINVOQ is 15 mg once daily. 2.

Recommended Dosage in Psoriatic Arthritis Pediatric Patients to Less Than 18 Years of Age The recommended dosage is based on body weight ( Table 1 ).

Table 1: RINVOQ/RINVOQ LQ Dosage for Pediatric Patients 2 Years to Less Than 18 Years of Age with Psoriatic Arthritis Patient Weight RINVOQ LQ RINVOQ 10 kg to less than 20 kg 3 mg (3 mL oral solution) twice daily Not recommended 20 kg to less than 30 kg 4 mg (4 mL oral solution) twice daily Not recommended 30 kg and greater 6 mg (6 mL oral solution) twice daily 15 mg (one 15 mg tablet) once daily RINVOQ LQ oral solution is not substitutable with RINVOQ extended-release tablets.

Adults 18 Years of Age and Older The recommended dosage of RINVOQ is 15 mg once daily. 2.5 Recommended Dosage in Atopic Dermatitis Pediatric Patients 12 Years of Age and Older Weighing at Least 40 kg and Adults Less Than 65 Years of Age Initiate treatment with RINVOQ 15 mg once daily.

If an adequate response is not achieved, consider increasing the dosage to 30 mg once daily.

RINVOQ if an adequate response is not achieved with the 30 mg dose.

Use the lowest effective dose needed to maintain response.

Adults 65 Years of Age and Older The recommended dosage of RINVOQ is 15 mg once daily. 2.6 Recommended Dosage in Ulcerative Colitis Adult Patients: Induction The recommended induction dosage of RINVOQ is 45 mg once daily for 8 weeks.

Maintenance The recommended dosage of RINVOQ for maintenance treatment is 15 mg once daily.

A dosage of 30 mg once daily may be considered for patients with refractory, severe or extensive disease.

Use the lowest effective dosage needed to maintain response. 2.7 Recommended Dosage in Crohn’s Disease Adult Patients: Induction The recommended induction dosage of RINVOQ is 45 mg once daily for 12 weeks.

Use the lowest effective dosage needed to maintain response. 2.

Recommended Dosage in Ankylosing Spondylitis The recommended dosage of RINVOQ is 15 mg once daily. 2.

Recommend ed Dosage in Non-radiographic Axial Spondyloarthritis The recommended dosage of RINVOQ is 15 mg once daily. 2.

Recommended Dosage in Polyarticular Juvenile Idiopathic Arthritis The recommended dosage is based on body weight (Table 2).

Table 2: RINVOQ/RINVOQ LQ Dosage for Patients 2 years and older with pJIA Patient Weight RINVOQ LQ RINVOQ 10 kg to less than 20 kg 3 mg (3 mL oral solution) twice daily Not recommended 20 kg to less than 30 kg 4 mg (4 mL oral solution) twice daily Not recommended 30 kg and greater 6 mg (6 mL oral solution) twice daily 15 mg (one 15 mg tablet) once daily RINVOQ LQ oral solution is not substitutable with RINVOQ extended-release tablets.

Changes between RINVOQ LQ oral solution and RINVOQ extended-release tablets should be made by the health care provider. 2.11 Recommended Dosage in Giant Cell Arteritis The recommended dosage of RINVOQ is 15 mg once daily in combination with a tapering course of corticosteroids.

RINVOQ 15 mg once daily can be used as monotherapy following discontinuation of corticosteroids. 2.1 2 Recommended Dosage in Patients with Renal Impairment or Hepatic Impairment Renal Impairment Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Non-radiographic Axial Spondyloarthritis, pJIA, and Giant Cell Arteritis: No dosage adjustment is needed for patients with mild, moderate, or severe renal impairment.

For patients with severe renal impairment [estimated glomerular filtration rate (eGFR) 15 to < 30 mL/min/1.73m 2 ] the recommended dosage of RINVOQ is 15 mg once daily.

No dosage adjustment is needed for patients with mild or moderate renal impairment (eGFR ≥ 30 mL/min/1.73m 2 ).

RINVOQ is not recommended for use in patients with end stage renal disease (eGFR < 15 mL/min/1.73m 2 ) .

For patients with severe renal impairment (eGFR to < 30 mL/min/1.73m 2 ), the recommended dosage of RINVOQ is:

• Induction: 30 mg once daily for 8 weeks.

• Maintenance: 15 mg once daily No dosage adjustment is needed for patients with mild or moderate renal impairment (eGFR ≥ 30 mL/min/1.73m 2 ).

RINVOQ is not recommended for use in patients with end stage renal disease (eGFR < 15 mL/min/1.73m 2 ) .

Crohn’s Disease: For patients with severe renal impairment (eGFR to < 30 mL/min/1.73m 2 ), the recommended dosage of RINVOQ is:

• Induction: 30 mg once daily for 12 weeks.

RINVOQ/RINVOQ LQ is not recommended for use in patients with severe hepatic impairment (Child-Pugh C) .

Arthritis, Psoriatic Arthritis, Atopic Dermatitis, Ankylosing Spondylitis, Non-radiographic Axial Spondyloarthritis, pJIA, and Giant Cell Arteritis: No dosage adjustment is needed for patients with mild or moderate hepatic impairment (Child-Pugh A or B).

For patients with mild to moderate hepatic impairment (Child-Pugh A or B) the recommended dosage of RINVOQ is: Induction: 30 mg once daily for 8 weeks Maintenance: 15 mg once daily Crohn’s Disease: For patients with mild to moderate hepatic impairment (Child-Pugh A or B) the recommended dosage of RINVOQ is: Induction: 30 mg once daily for 12 weeks Maintenance: 15 mg once daily 2. 1 3 Dosage Modifications Due to Drug Interactions Rheumatoid Arthritis, Psoriatic Arthritis, Ankylos ing Spondylitis, Non-radiographic Axial Spondyloarthritis, pJIA, and Giant Cell Arteritis No dosage adjustment is needed in patients receiving strong CYP3A4 inhibitors.

Atopic Dermatitis The recommended dosage of

RINVOQ in patients receiving strong CYP3A4 inhibitors is 15 mg once daily.

Ulcerative Colitis The recommended dosage of

RINVOQ in patients with ulcerative colitis receiving strong CYP3A4 inhibitors [see Dr.

RINVOQ extended-release tablets are supplied as: 15 mg: purple, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a15’ on one side. 30 tablets in a bottle; NDC: 0074-2306-30 30 mg: red, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a30’ on one side. 30 tablets in a bottle; NDC: 0074-2310-30 45 mg: yellow to mottled yellow, biconvex oblong, with dimensions of 14 x 8 mm, and debossed with ‘a45’ on one side. 28 tablets in a bottle; NDC: 0074-1043-28 RINVOQ LQ oral solution is supplied as: A 1 mg/mL oral solution in HDPE bottles with a child-resistant cap.

Each bottle contains a labeled volume of 180 mL of clear, colorless to light yellow solution.

The bottle is packaged in a carton with one press-in bottle adapter and one 10 mL oral dosing syringe; NDC: 0074-2320-01 Storage and Handling RINVOQ extended-release tablets Store at 2˚C to 25˚C (36˚F to 77˚F).

Store in the original bottle in order to protect from moisture.

RINVOQ LQ oral solution

Store between 2°C to 30°C (36°F to 86°F).

Discard remaining oral solution 60 days after opening the bottle.

Surveillance Program There is a pregnancy surveillance program for RINVOQ/RINVOQ LQ that monitors pregnancy outcomes in women exposed to RINVOQ/RINVOQ LQ.

If RINVOQ/RINVOQ LQ exposure occurs during pregnancy, healthcare providers or patients should report the pregnancy by calling 1-800-633-9110.

Available data from the pharmacovigilance safety database and postmarketing case reports on use of RINVOQ in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage.

Based on animal studies, RINVOQ/RINVOQ LQ has the potential to adversely affect a developing fetus.

Advise patients of reproductive potential and pregnant patients of the potential risk to the fetus.

In animal embryo-fetal development studies, oral upadacitinib administration to pregnant rats and rabbits at exposures equal to or greater than approximately 1.6 and 15 times the 15 mg tablet dose, 0.8 and 7.6 times the 30 mg tablet dose, and 0.6 and 5.6 times the maximum recommended human dose (MRHD) of 45 mg (on an AUC basis) resulted in dose-related increases in skeletal malformations (rats only), an increased incidence of cardiovascular malformations (rabbits only), increased post-implantation loss (rabbits only), and decreased fetal body weights in both rats and rabbits.

No developmental toxicity was observed in pregnant rats and rabbits treated with oral upadacitinib during organogenesis at exposures approximately 0.29 and 2.2 times the 15 mg dose, 0.15 times and 1.1 times the 30 mg dose, and at 0.11 and 0.82 times the MRHD (on an AUC basis).

In a pre.

• and post-natal development study in pregnant female rats, oral upadacitinib administration at exposures approximately 3 times the 15 mg dose, 1.4 times the 30 mg dose, and the same as the MRHD (on an AUC basis) resulted in no maternal or developmental toxicity.

The background risks of major birth defects and miscarriage for the indicated populations are unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriages are 2-4% and 15-20%, respectively.

Maternal and/or Embryo/Fetal Risk Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with rheumatoid arthritis or inflammatory bowel disease.

Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth.

In an oral embryo-fetal development study, pregnant rats received upadacitinib at doses of 5, 25, and 75 mg/kg/day during the period of organogenesis from gestation day to 17.

Upadacitinib was teratogenic (skeletal malformations that consisted of misshapen humerus and bent scapula) at exposures equal to or greater than approximately 1.7 times the 15 mg tablet dose, 0.9 times the 30 mg tablet dose, and 0.6 times the MRHD (on an AUC basis at maternal oral doses of 5 mg/kg/day and higher).

Additional skeletal malformations (bent forelimbs/hindlimbs and rib/vertebral defects) and decreased fetal body weights were observed in the absence of maternal toxicity at an exposure approximately 84 times the 15 mg dose, 43 times the 30 mg dose, and 31 times the MRHD (on an AUC basis at a maternal oral dose of 75 mg/kg/day).

In a second oral embryo-fetal development study, pregnant rats received upadacitinib at doses of 1.5 and 4 mg/kg/day during the period of organogenesis from gestation day to 17.

Upadacitinib was teratogenic (skeletal malformations that included bent humerus and scapula) at exposures approximately 1.6 times the 15 mg dose, 0.8 times the 30 mg dose, and 0.6 times the MRHD (on an AUC basis at maternal oral doses of 4 mg/kg/day).

No developmental toxicity was observed in rats at an exposure approximately 0.29 times the 15 mg tablet dose, 0.15 times the 30 mg tablet dose, and 0.11 times the MRHD (on an AUC basis at a maternal oral dose of 1.5 mg/kg/day).

In an oral embryo-fetal developmental study, pregnant rabbits received upadacitinib at doses of 2.5, 10, and 25 mg/kg/day during the period of organogenesis from gestation day to 19.

Embryolethality, decreased fetal body weights, and cardiovascular malformations were observed in the presence of maternal toxicity at an exposure approximately 15 times the 15 mg tablet dose, 7.6 times the 30 mg tablet dose, and 5.6 times the MRHD (on an AUC basis at a maternal oral dose of 25 mg/kg/day).

Embryolethality consisted of increased post-implantation loss that was due to elevated incidences of both total and early resorptions.

No developmental toxicity was observed in rabbits at an exposure approximately 2.2 times the 15 mg tablet dose, 1.1 times the 30 mg tablet dose, and 0.82 times the MRHD (on an AUC basis at a maternal oral dose of 10 mg/kg/day).

In an oral pre.

• and post-natal development study, pregnant female rats received upadacitinib at doses of 2.5, 5, and 10 mg/kg/day from gestation day 6 through lactation day 20.

No maternal or developmental toxicity was observed in either mothers or offspring, respectively, at an exposure approximately 3 times the 15 mg tablet dose, 1.4 times the 30 mg tablet dose, and at approximately the same exposure as the MRHD (on an AUC basis at a maternal oral dose of 10 mg/kg/day).

Spondylitis, Non-radiographic Axial Spondyloarthritis, Ulcerative Colitis, and Crohn’s Disease The safety and effectiveness of RINVOQ/RINVOQ LQ in pediatric patients with ankylosing spondylitis, non-radiographic axial spondyloarthritis, ulcerative colitis, or Crohn’s disease have not been established.

Polyarticular Juvenile Idiopathic Arthritis and Psoriatic Arthritis The safety and effectiveness of RINVOQ/RINVOQ LQ in pediatric patients to less than 18 years of age with pJIA and psoriatic arthritis have been established.

The use of

RINVOQ/RINVOQ LQ in these age groups is supported by evidence from well-controlled studies of RINVOQ in adults with rheumatoid arthritis and psoriatic arthritis, pharmacokinetic data from adult patients with rheumatoid arthritis and psoriatic arthritis and 51 pediatric patients with JIA with active polyarthritis, and safety data from 83 pediatric patients to < 18 years of age with JIA with active polyarthritis.

Upadacitinib plasma exposures in pediatric patients with pJIA and psoriatic arthritis at the recommended dosage are predicted to be comparable to those observed in adults with rheumatoid arthritis and psoriatic arthritis based on population pharmacokinetic modeling and simulation.

The safety and effectiveness of

RINVOQ/RINVOQ LQ in pediatric patients less than 2 years of age with pJIA or psoriatic arthritis have not been established.

Atopic Dermatitis The safety and effectiveness of RINVOQ in pediatric patients 12 years of age and older weighing at least 40 kg with atopic dermatitis have been established.

A total of 344 pediatric patients aged to 17 years with moderate to severe atopic dermatitis were randomized across three trials (AD-1, AD-2 and AD-3) to receive either RINVOQ 15 mg (N=114) or 30 mg (N=114) or matching placebo (N=116) in monotherapy or combination with topical corticosteroids.

Efficacy was consistent between the pediatric patients and adults.

The adverse reaction profile in the pediatric patients was similar to the adults.

RINVOQ in pediatric patients less than 12 years of age with atopic dermatitis have not been established.

The safety and effectiveness of RINVOQ

LQ in pediatric patients with atopic dermatitis have not been established.

Of the 4381 patients treated in the five clinical trials, a total of 906 rheumatoid arthritis patients were 65 years of age or older, including 146 patients 75 years and older.

Of the 1827 patients treated in the two psoriatic arthritis Phase 3 clinical trials, a total of 274 patients were 65 years of age or older, including 34 patients 75 years and older.

No differences in effectiveness were observed between these patients and younger patients; however, there was a higher rate of overall adverse events, including serious infections, in patients 65 years of age and older.

Of the 2583 patients treated in the three Phase 3 clinical trials, a total of 120 patients with atopic dermatitis were 65 years of age or older, including 6 patients 75 years of age.

No differences in effectiveness were observed between these patients and younger patients; however, there was a higher rate of serious infections and malignancies in those patients 65 years of age or older in the 30 mg dosing group in the long-term trials.

Of the 1097 patients treated in the controlled clinical trials, a total of 95 patients with ulcerative colitis were 65 years and older.

Clinical studies of

RINVOQ did not include sufficient numbers of patients 65 years of age and older with ulcerative colitis to determine whether they respond differently from younger adult patients.

Crohn’s Disease Of the 1021 patients who were treated in the controlled induction clinical trials, a total of 39 patients with Crohn’s disease were 65 years of age or older, and no patients were 75 years of age or older.

RINVOQ did not include sufficient numbers of patients 65 years of age and older with Crohn’s disease to determine whether they respond differently from younger adult patients.

Of the 607 patients treated in the controlled clinical trials, a total of 32 patients with ankylosing spondylitis were 65 years and older.

RINVOQ did not include sufficient numbers of patients 65 years of age and older with ankylosing spondylitis to determine whether they respond differently from younger adult patients.

Of the 313 patients treated in a phase 3 clinical trial, a total of 9 patients with non-radiographic axial spondyloarthritis were 65 years and older.

RINVOQ did not include sufficient numbers of patients 65 years of age and older with non-radiographic axial spondyloarthritis to determine whether they respond differently from younger adult patients.