Dosing & MOA | Rheumatoid Arthritis | RINVOQ® (upadacitinib)

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

Rheumatoid Arthritis

Psoriatic Arthritis

Ankylosing Spondylitis

Non-radiographic Axial Spondyloarthritis

Atopic Dermatitis

Ulcerative Colitis

Crohn’s Disease

Visit RINVOQhcp.com

Plaque Psoriasis

Psoriatic Arthritis

Crohn's Disease

Visit SKYRIZIhcp.com

Please see Important Safety Information, including BOXED WARNING on Serious Infections and Malignancy.

Hidradenitis Suppurativa

Juvenile Idiopathic Arthritis

Pediatric Crohn's Disease

Pediatric Ulcerative Colitis

Pediatric Uveitis

Uveitis (Adult)

Other Indications

Visit HUMIRApro.com

US-MULT-230356

Immunology Therapies

Full Prescribing Information

Patient Site

For moderate to severe rheumatoid arthritis (RA) in adult TNFi-IR patients¹

IR=intolerance or inadequate response; TNFi=tumor necrosis factor inhibitor

A ONCE-DAILY ORAL THERAPY
STUDIED WITH OR WITHOUT MTX IN RA¹

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.¹

Download Dosing Guide

RINVOQ is a 15 mg extended-release pill.¹
Take one pill 1 time a day with or without food.
Advise patients to avoid food or drink containing grapefruit during treatment with RINVOQ.
Swallow pill whole. Do not split, crush, or chew.
Instruct patients to notify their healthcare provider if they repeatedly notice intact RINVOQ tablet or fragments in stool or ostomy output.
Store at 36˚F to 77˚F (2˚C to 25˚C) in the original bottle in order to protect from moisture.
In clinical trials, RINVOQ mean terminal elimination half-life ranged from 8-14 hours.

RINVOQ National Drug Code (NDC) number: 0074-2306-30

Awarded the Arthritis Foundation Ease of Use Commendation,² our innovative bottle cap includes:

Wide, easy-to-grip texture
Embedded tool that seamlessly punctures the foil liner to simplify medication access

IR=intolerance or inadequate response; MTX=methotrexate; RA=rheumatoid arthritis; TNFi=tumor necrosis factor inhibitor

Lab Monitoring
and
treatment considerations¹

TREATMENT WITH RINVOQ SHOULD NOT BE INITIATED, OR SHOULD BE INTERRUPTED IF:

Absolute neutrophil count <1000 cells/mm3*;Absolute lymphocyte count <500 cells/mm3*; Hemoglobin levels <8 g/dL*;Liver enzyme elevations and a drug-induced liver injury is suspected*; Patient has or develops a serious or opportunistic infection*

*Treatment can be initiated or restarted after levels return above specified values, drug-induced liver injury diagnosis is excluded, or infection is controlled.

In RA, PsA, AS, and nr‑axSpA:

No dose adjustment is required for mild, moderate or severe renal impairment.¹

No dose adjustment is required for mild or moderate hepatic impairment.¹

RINVOQ is not recommended in patients with:

Active hepatitis B or hepatitis C
Severe hepatic impairment (Child‑Pugh C)

RINVOQ has not been studied in end‑stage renal disease (eGFR <15 mL/min/1.73m²)

HYPERSENSITIVITY:¹ RINVOQ is contraindicated in patients with known hypersensitivity to upadacitinib or any of its excipients. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy.

Rinvoq is a JAK inhibitor¹

Why JAKs are important in RA^3-7

Pro-inflammatory cytokines use immune signaling networks, such as the JAK-STAT pathway, to communicate with the cell nucleus. When dysregulated, as in RA, these signals increase the inflammatory response, leading to cycles of chronic inflammation, presenting as pain, swelling, and progressive joint destruction.

Overview of the JAK-STAT pathway^3,4,6,8,9

A cytokine binds to a specific receptor on the cell surface...
...triggering JAK recruitment and activation inside the cell.
The activated JAKs recruit and activate STATs...
...which in turn transmit the signal into the cell nucleus...
...initiating an inflammatory response that continues the cycle of pathologic inflammation.

*The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.¹

By inactivating JAK, RINVOQ is thought to block the recruitment, phosphorylation, and activation of STATs preventing the pro‑inflammatory cytokine signal from reaching the nucleus and inhibiting pro‑inflammatory processes associated with the JAK‑STAT pathway.

*The relevance of inhibition of specific JAK enzymes to therapeutic effectiveness is not currently known.¹

Based on enzymatic and cellular assays, RINVOQ demonstrated greater inhibitory potency for JAK‑1 vs JAK‑2, JAK‑3, and TYK‑2.^1,*

EPO=erythropoietin; GH=growth hormone; GM‑CSF=granulocyte‑macrophage colony‑stimulating factor; IFN=interferon; IL=interleukin; JAK=Janus kinase; PsA=psoriatic arthritis; STAT=signal transducer and activator of transcription; TPO=thrombopoietin; TYK=tyrosine kinase

Discover how RINVOQ Complete can provide
exceptional access and support

SEE ACCESS & SUPPORT

IMPORTANT SAFETY INFORMATION & INDICATIONS¹

INDICATIONS¹

RINVOQ is indicated for the treatment of:

Moderately to severely active rheumatoid arthritis (RA) in adults who have had an inadequate response or intolerance to one or more tumor necrosis factor (TNF) blockers.
Active psoriatic arthritis (PsA) in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Active ankylosing spondylitis (AS) in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation in adults who have had an inadequate response or intolerance to TNF blocker therapy.

Refractory, moderate to severe atopic dermatitis (AD) in adults and pediatric patients 12 years of age and older whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants.

Moderately to severely active ulcerative colitis (UC) in adults who have had an inadequate response or intolerance to one or more TNF blockers.

Moderately to severely active Crohn's disease (CD) in adults who have had an inadequate response or intolerance to one or more TNF blockers.

Limitations of Use: RINVOQ is not recommended for use in combination with other JAK inhibitors, biological therapies for ulcerative colitis or Crohn’s disease, or with potent immunosuppressants such as azathioprine and cyclosporine.

SERIOUS INFECTIONS

Patients treated with RINVOQ are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants, such as methotrexate or corticosteroids. If a serious infection develops, interrupt RINVOQ until the infection is controlled.

Reported infections include:

Active tuberculosis (TB), which may present with pulmonary or extrapulmonary disease. Test patients for latent TB before RINVOQ use and during therapy. Consider treatment for latent TB infection prior to RINVOQ use.
Invasive fungal infections, including cryptococcosis and pneumocystosis.
Bacterial, viral, including herpes zoster, and other infections due to opportunistic pathogens.

Carefully consider the risks and benefits of treatment with RINVOQ prior to initiating therapy in patients with chronic or recurrent infection. Monitor patients closely for the development of signs and symptoms of infection during and after treatment with RINVOQ, including the possible development of TB in patients who tested negative for latent TB infection prior to initiating therapy.

MORTALITY

In a large, randomized, postmarketing safety study comparing another Janus kinase (JAK) inhibitor with tumor necrosis factor (TNF) blockers in rheumatoid arthritis (RA) patients ≥50 years old with at least one cardiovascular (CV) risk factor, a higher rate of all-cause mortality, including sudden CV death, was observed with the JAK inhibitor. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ.

MALIGNANCIES

Lymphoma and other malignancies have been observed in patients treated with RINVOQ.

In a large, randomized, postmarketing safety study comparing another JAK inhibitor with TNF blockers in RA patients, a higher rate of malignancies (excluding non-melanoma skin cancer [NMSC]), lymphomas, and lung cancer (in current or past smokers) was observed with the JAK inhibitor. Patients who are current or past smokers are at additional increased risk.

With RINVOQ, consider the benefits and risks for the individual patient prior to initiating or continuing therapy, particularly in patients with a known malignancy (other than a successfully treated 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 RINVOQ. 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

In a large, randomized, postmarketing study comparing another JAK inhibitor with TNF blockers in RA patients ≥50 years old with at least one CV risk factor, a higher rate of major adverse cardiovascular events (MACE) (defined as cardiovascular death, myocardial infarction, and stroke) was observed with the JAK inhibitor. Patients who are current or past smokers are at additional increased risk. Discontinue RINVOQ in patients that have experienced a myocardial infarction or stroke.

Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with RINVOQ, particularly in patients who are current or past smokers and patients with other CV risk factors. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur.

THROMBOSIS

Thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis have occurred in patients treated with JAK inhibitors used to treat inflammatory conditions. Many of these adverse events were serious and some resulted in death.

In a large, randomized, postmarketing study comparing another JAK inhibitor to TNF blockers in RA patients ≥50 years old with at least one CV risk factor, a higher rate of thrombosis was observed with the JAK inhibitor. Avoid RINVOQ in patients at risk. Patients with symptoms of thrombosis should discontinue RINVOQ and be promptly evaluated.

HYPERSENSITIVITY

RINVOQ 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 RINVOQ in clinical trials. If a clinically significant hypersensitivity reaction occurs, discontinue RINVOQ and institute appropriate therapy.

GASTROINTESTINAL PERFORATIONS

Gastrointestinal (GI) perforations have been reported in clinical trials with RINVOQ. Monitor RINVOQ-treated patients who may be at risk for gastrointestinal perforation (e.g., patients with a history of diverticulitis and patients taking NSAIDs or corticosteroids). Promptly evaluate patients presenting with new onset abdominal pain for early identification of GI perforation.

LABORATORY ABNORMALITIES

Neutropenia

Treatment with RINVOQ was associated with an increased incidence of neutropenia (absolute neutrophil count [ANC] <1000 cells/mm³). Treatment with RINVOQ is not recommended in patients with an ANC <1000 cells/mm³. Evaluate neutrophil counts at baseline and thereafter according to routine patient management.

Lymphopenia

Absolute lymphocyte counts (ALC) <500 cells/mm³ were reported in RINVOQ-treated patients. Treatment with RINVOQ is not recommended in patients with an ALC <500 cells/mm³. Evaluate at baseline and thereafter according to routine patient management.

Anemia

Decreases in hemoglobin levels to <8 g/dL were reported in RINVOQ-treated patients. Treatment should not be initiated or should be interrupted in patients with hemoglobin levels <8 g/dL. Evaluate at baseline and thereafter according to routine patient management.

Lipids

Treatment with RINVOQ was associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. Manage patients according to clinical guidelines for the management of hyperlipidemia. Evaluate patients 12 weeks after initiation of treatment and thereafter according to the clinical guidelines for hyperlipidemia.

Liver enzyme elevations

Treatment with RINVOQ was associated with increased incidence of liver enzyme elevation compared to placebo. Evaluate at baseline and thereafter according to routine patient management. Prompt investigation of the cause of liver enzyme elevation is recommended to identify potential cases of drug-induced liver injury. If increases in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) are observed during routine patient management and drug-induced liver injury is suspected, RINVOQ should be interrupted until this diagnosis is excluded.

EMBRYO-FETAL TOXICITY

Based on findings in animal studies, RINVOQ may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with RINVOQ and for 4 weeks after the final dose. Verify pregnancy status of females of reproductive potential prior to starting treatment with RINVOQ.

VACCINATION

Avoid use of live vaccines during, or immediately prior to, RINVOQ therapy. Prior to initiating RINVOQ, patients should be brought up to date on 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 RINVOQ. Most reports described anatomic or functional GI conditions with shortened GI transit times. Instruct patients to contact their healthcare provider if medication residue is observed repeatedly. Monitor patients clinically and consider alternative treatment if there is an inadequate therapeutic response.

LACTATION

There are no data on the presence of RINVOQ in human milk, the effects on the breastfed infant, or the effects on milk production. Available data in animals have shown the excretion of RINVOQ in milk. Advise patients that breastfeeding is not recommended during treatment with RINVOQ and for 6 days after the last dose.

HEPATIC IMPAIRMENT

RINVOQ is not recommended for use in patients with severe hepatic impairment.

ADVERSE REACTIONS

The most common adverse reactions in RINVOQ clinical trials were upper respiratory tract infections, herpes zoster, herpes simplex, bronchitis, nausea, cough, pyrexia, acne, headache, increased blood creatine phosphokinase, hypersensitivity, folliculitis, abdominal pain, increased weight, influenza, fatigue, neutropenia, myalgia, influenza-like illness, elevated liver enzymes, rash, and anemia.

Inform patients that retinal detachment has been reported in clinical trials with RINVOQ. Advise patients to immediately inform their healthcare provider if they develop any sudden changes in vision while receiving RINVOQ.

Dosage Forms and Strengths: RINVOQ is available in 15 mg, 30 mg, and 45 mg extended-release tablets.

US-RNQ-230518

Please see full Prescribing Information.

REFERENCES

RINVOQ [package insert]. North Chicago, IL: AbbVie Inc.
Bradley Fain W. Abbvie child resistant special feature closure packaging evaluation report of consumer product accessibility for users with arthritis. Intuitive Design Applied Research Institute, Atlanta GA (2017).
Malemud CJ. The role of the JAK/STAT signal pathway in rheumatoid arthritis. Ther Adv Musculoskelet Dis. 2018;10(5‑6):117‑127.
Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. Erratum to: JAK‑STAT signaling as a target for inflammatory and autoimmune
diseases: current and future prospects. Drugs. 2017;77(11):1261.
Virtanen AT, Haikarainen T, Raivola J, Silvennoinen O. Selective JAKinibs: prospects in inflammatory and autoimmune diseases. BioDrugs. 2019;33(1):15‑32.
Malemud CJ. Suppression of autoimmune arthritis by small molecule inhibitors of the JAK/STAT pathway. Pharmaceuticals 2010;3(5):1446‑1455.
Salaffi F, Giacobazzi G, Di Carlo M. Chronic pain in inflammatory arthritis: mechanisms, metrology, and emerging targets—a focus on the JAK-STAT pathway. Pain Research and Management. 2018;2018:1‑14.
Winthrop KL. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol. 2017;13(5):320.
Alunno A, Carubbi F, Giacomelli R, Gerli R. Cytokines in the pathogenesis of rheumatoid arthritis: new players and therapeutic targets. BMC Rheumatol. 2017;1:3.
Patterson H, Nibbs R, McInnes I, Siebert S. Protein kinase inhibitors in the treatment of inflammatory and autoimmune diseases. Clinical & Experimental Immunology. 2014;176(1):1‑10.
Parmentier JM, Voss J, Graff C, et al. In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC
Rheumatol. 2018;2:23.
Fleischmann R, Bessette L, Sparks J et al. Safety and efficacy of upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biologic DMARDs: results through 5 years from the SELECT-BEYOND study. Poster presented at: the American College of Rheumatology Convergence, November 10-14, 2022, Philadelphia, PA, USA.
Smolen JS, Emery P, Rigby W, et al. Upadacitinib as monotherapy in patients with rheumatoid arthritis and prior inadequate response to methotrexate: results at 260 weeks from the SELECT-MONOTHERAPY study. Poster presented at: The European Congress of Rheumatology, 31 May - 3 June 2023, Milan, Italy.
Smolen JS, Pangan AL, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet. 2019;393(10188):2‍3‍0‍3‍-‍2‍3‍1‍1.
Data on File. ABVRRTI72945.

RA patients met ACR20 at Week 12 or 14 (Primary Endpoints) and Disease Control through Remission
(DAS28-CRP <2.6)* at Weeks 12 or 14 and observed up to 5 years. Explore the Data

*Clinical remission does not mean drug-free remission or complete absence of disease activity

Clinical Remission

Remission + LDA at Weeks 12 and 14

Remission out to ~5 years

LDA out to ~5 years

Safety Profile

Data Up to 12 Months

Long-term Exposure Data

Monitoring & Dose Interruptions

Important Safety Information

Access & Support

Commercial Access

RINVOQ Complete

How To Enroll Patients

Downloadable Resources

Dosing & MOA

Dosing

Monitoring

Mechanism of Action

Important Safety Information

Prescribing Information (English)

Información en español

INDICATIONS & LIMITATION OF USE¹

RINVOQ is indicated for the treatment of:

Moderately to severely active rheumatoid arthritis (RA) in adults who have had an inadequate response or intolerance to one or more
tumor necrosis factor (TNF) blockers.
Active psoriatic arthritis (PsA) in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Active ankylosing spondylitis (AS) in adults who have had an inadequate response or intolerance to one or more TNF blockers.

IMPORTANT SAFETY INFORMATION¹

WARNING: Serious Infections, Mortality, Malignancies, Major Adverse Cardiovascular Events, and Thrombosis.

SERIOUS INFECTIONS

IMPORTANT SAFETY INFORMATION¹

WARNING: Serious Infections, Mortality, Malignancies, Major Adverse Cardiovascular Events, and Thrombosis.

SERIOUS INFECTIONS

Patients treated with RINVOQ are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant

INDICATIONS & LIMITATION OF USE¹

RINVOQ is indicated for the treatment of:

Moderately to severely active rheumatoid arthritis (RA) in adults who have had an inadequate response or intolerance to one or more
tumor necrosis factor (TNF) blockers.
Active psoriatic arthritis (PsA) in adults who have had an inadequate response or intolerance to one or more TNF blockers.
Active ankylosing spondylitis (AS) in adults who have had an inadequate response or intolerance to one or more TNF blockers.

IMPORTANT SAFETY INFORMATION¹

WARNING: Serious Infections, Mortality, Malignancies, Major Adverse Cardiovascular Events, and Thrombosis.

SERIOUS INFECTIONS

IMPORTANT SAFETY INFORMATION¹

WARNING: Serious Infections, Mortality, Malignancies, Major Adverse Cardiovascular Events, and Thrombosis.

SERIOUS INFECTIONS