PSORIATIC ARTHRITIS
The safety profile of RINVOQ in PsA was consistent with previously reported results in rheumatoid arthritis.1-2
SELECT-PsA 1: Adverse events through Week 242
The most common AEs were upper respiratory tract infection, nasopharingitis, blood CPK increase, ALT increase and AST increase2
*A higher incidence of acne and bronchitis was observed in patients treated with upadacitinib 15 mg (1.3% and 3.9%, respectively) compared to placebo (0.3% and 2.7%, respectively). In patients treated with RINVOQ in combination with methotrexate therapy compared to patients treated with monotherapy, a higher rate of serious infections (2.6 events per 100 patient years and 1.3 events per 100 patient years, respectively) and hepatic transaminase elevations (ALT elevations Grade 3 and higher rates 1.4% and 0.4%, respectively) was observed. There was a higher rate of serious infections in patients ≥ 65 years of age, although data are limited.2
**Lung cancer metastasis.
Treatment Emergent AEs reported in ≥5% of patients in any treatment arm through Week 24.
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CPK, creatine phosphokinase; MACE, major adverse cardiovascular event; MTX: methotrexate; NMSC, non-melanoma skin cancer; PYs: patient years; QD, once daily; SAE, serious adverse event; VTE, venous thromboembolism
SELECT-PsA 2: Adverse events through Week 243
Summary of the RINVOQ safety profile
The most commonly reported adverse reactions with RINVOQ 15 mg were upper respiratory tract infections, blood creatinine phosphokinase (CPK) increased, alanine transaminase increased, bronchitis, nausea, neutropaenia, cough, aspartate transaminase increased, and hypercholesterolaemia. The most common serious adverse reactions were serious infections (see RINVOQ Summary of Product Characteristics for more details).1
Adverse drug reactions
The following table of adverse reactions is based on experience from clinical studies.1
The frequency of adverse reactions is defined using the following convention: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.1
aPresented as grouped term.
bIn atopic dermatitis trials, the frequency of bronchitis, hypercholesterolaemia, hyperlipidaemia, ALT increased, and AST increased was uncommon.
cIn rheumatologic disease trials, the frequency was common for acne and uncommon for urticaria.
dIn ulcerative colitis trials, the frequency was common for acne; abdominal pain was less frequent for upadacitinib than for placebo.
eSerious hypersensitivity reactions including anaphylactic reaction and angioedema.
fMost events reported as basal cell carcinoma and squamous cell carcinoma of skin.
For more detailed safety information, please see the RINVOQ Prescribing Information link at the top of the page, or for complete product information, the RINVOQ Summary of Product Characteristics.
Screening your patients
Like many other PsA treatments, RINVOQ is associated with an increased rate of infections compared to placebo. The benefits and risks of treatment with RINVOQ should be considered prior to initiating therapy in patients with active, chronic, or recurrent infections.1
- Serious infections: RINVOQ should not be initiated in patients with an active, serious infection, including localised infections. Closely monitor patients for the development of signs and symptoms of infection during and after treatment with RINVOQ.
- Tuberculosis: Patients should be screened for tuberculosis (TB) before starting treatment with RINVOQ. Treatment should not be initiated in patients with active TB. Anti-TB therapy should be considered prior to treatment initiation of RINVOQ in patients with previously untreated TB or in patients with risk factors for TB infection. Consultation with a physician with expertise in the treatment of TB is recommended to aid in the decision about whether initiating anti-TB therapy is appropriate for an individial patient.
- Viral reactivation: Screening for viral hepatitis and monitoring for reactivation should be performed before starting and during treatment with RINVOQ. Patients who were positive for hepatitis C antibody and hepatitis C virus RNA were excluded from clinical studies. Patients who were positive for hepatitis B surface antigen or hepatitis B virus DNA were excluded from clinical studies. If hepatitis B virus DNA is detected while receiving RINVOQ, a liver specialist should be consulted. If a patient develops herpes zoster, consider interruption of RINVOQ therapy until the episode resolves.
- Non-melanoma skin cancer: Periodic skin examination is recommended for all patients, particularly those with risk factors for skin cancer.
- Vaccinations: Use of live, attenuated vaccines during, or immediately prior to, RINVOQ treatment is not recommended. Prior to initiating RINVOQ, it is recommended that patients be brought up to date with all immunisations, including prophylactic zoster vaccinations, in agreement with current immunization guidelines.
- Venous thromboembolism: Rinvoq should be used with caution in patients with known VTE risk factors. Patients should be re-evaluated periodically during Rinvoq treatment to assess for changes in VTE risk. Promptly evaluate patients with signs and symptoms of VTE and discontinue Rinvoq in patients with suspected VTE.
- Gastrointestinal perforations: Rinvoq should be used with caution in patients who may be at risk for gastrointestinal perforation (e.g., patients with diverticular disease, a history of diverticulitis, or who are taking NSAIDs, corticosteroids, or opioids). Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis or gastrointestinal perforation.
Contraindications
- Hypersensitivity to the active substance or to any of the excipients listed (RINVOQ SmPC section 6.1)
- Active TB or active serious infections (RINVOQ SmPC section 4.4)
- Severe hepatic impairment
- Pregnancy
Monitoring requirements
Treatment with RINVOQ should not be initiated, or should be interrupted if:1
- Absolute neutrophil count <1 x 109 cells/L*
- Absolute lymphocyte count <0.5 x 109 cells/L*
- Haemoglobin <8g/dL*
- Drug-induced liver injury is suspected
- Patient develops a serious or opportunistic infection
- A patient with an infection is not responding to antimicrobial therapy
Laboratory measures and monitoring guidance1
Renal impairment
No dose adjustment is required in patients with mild or moderate renal impairment. There are limited data on the use of RINVOQ in subjects with severe renal impairment. RINVOQ should be used with caution in patients with severe renal impairment.1
Hepatic impairment
No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. RINVOQ should not be used in patients with severe hepatic impairment.1
*Treatment may be initiated or restarted after levels return above specified values.
Lab abnormalities1
Hepatic transaminase elevations
Lipid elevations
Creatine phosphokinase (CPK)
Neutropaenia
In RA population: In placebo-controlled studies with background DMARDs, for up to 12/14 weeks, alanine transaminase (ALT) and aspartate transaminase (AST) elevations ≥3x upper limit of normal (ULN) in at least one measurement were observed in 2.1% and 1.5% of patients treated with RINVOQ, compared to 1.5% and 0.7%, respectively, of patients treated with placebo. Most cases of hepatic transaminase elevations were asymptomatic and transient.
In MTX-controlled studies, for up to 12/14 weeks, ALT and AST elevations ≥3x ULN in at least one measurement were observed in 0.8% and 0.4% of patients treated with RINVOQ, compared to 1.9% and 0.9%, respectively, of patients treated with MTX.
The pattern and incidence of elevation in ALT/AST remained stable over time including in long-term extension studies.
RINVOQ treatment was associated with dose-dependent increases in lipid parameters, including total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. There was no change in the LDL/HDL ratio. Elevations were observed at 2 to 4 weeks of treatment and remained stable with longer-term treatment.
In placebo-controlled studies with background DMARDs, for up to 12/14 weeks, increases in CPK were observed. CPK elevations >5x upper limit of normal (ULN) were reported in 1.0%, and 0.3% of patients over 12/14 weeks in the RINVOQ and placebo groups, respectively. Most elevations >5x ULN were transient and did not require treatment discontinuation. Mean CPK values increased by 4 weeks with a mean increase of 60 U/L at 12 weeks and then remained stable at an increased value thereafter, including with extended therapy.
In placebo-controlled studies with background DMARDs, for up to 12/14 weeks, decreases in neutrophil counts below 1 x 109 cells/L in at least one measurement occurred in 1.1% and <0.1% of patients in the RINVOQ and placebo groups, respectively. In clinical studies, treatment was interrupted in response to ANC <1 x 109 cells/L. Mean neutrophil counts decreased over 4 to 8 weeks. The decreases in neutrophil counts remained stable at a lower value than baseline over time, including with extended therapy.
In PsA population: Overall, the safety profile observed in patients with active PsA treated with RINVOQ 15 mg was consistent with the safety profile observed in patients with RA. A higher rate of serious infections (2.6 events per 100 patient-years and 1.3 events per 100 patient-years, respectively) and hepatic transaminase elevations (ALT elevations Grade 3 and higher rates 1.4% and 0.4%, respectively) was observed in patients treated with RINVOQ in combination with MTX therapy compared to patients treated with monotherapy.
Safety Information4
Important safety information for RINVOQ
You are also strongly advised to read the prescribing information (PI) which can be found at the top of this page
Before starting RINVOQ treatment, please note the following
1. RINVOQ should be initiated and supervised by physicians experienced in the treatment of psoriatic arthritis
2. RINVOQ should only be used if no suitable treatment alternatives are available in patients:
a. ≥65 years of age
b. With history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (e.g., current or previous long-time smokers)
c. With malignancy risk factors (e.g., current malignancy or history of malignancy)
3. Posology
Rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis
The recommended dose of upadacitinib is 15 mg once daily.
Consideration should be given to discontinuing treatment in patients with axial spondyloarthritis who have shown no clinical response after 16 weeks of treatment. Some patients with initial partial response may subsequently improve with continued treatment beyond 16 weeks.
Elderly
- There is an increased risk of MACE, malignancies, serious infections, and all-cause mortality in patients ≥65 years of age
- Only use RINVOQ in patients ≥65 years of age and older if no suitable treatment alternatives are available
- There is an increased risk of adverse reactions with RINVOQ 30 mg in patients ≥65 years of age and older
- The licensed dose in PsA is 15mg once daily
Concomitant use with other potent immunosuppressants
- Not recommended, as a risk of additive immunosuppression cannot be excluded
Concomitant use with strong CYP3A4 inhibitors and inducers
- Use with caution (see SmPC for dose adjustments), consider alternatives to strong inhibitors if used long-term and monitor for changes in disease activity if using strong inducers
Infections
- Do not use RINVOQ in active, serious and localised infections
- Consider the risks and benefits in patients with chronic/recurrent infection, those exposed to TB, those that have a history of opportunistic/serious infections, those that have resided or travelled in areas of endemic TB/mycoses or with underlying conditions that predispose them to infection
- Monitor for signs and symptoms of infection during and after treatment. Interrupt treatment if the patient shows signs and symptoms of serious or opportunistic infection. Resume treatment after control of serious infection with careful benefit-risk consideration. Patients who develop new infection require prompt diagnostic testing as appropriate for immunosuppressed patients and appropriate therapy. Monitor closely and interrupt treatment if the patient is not responding to appropriate antimicrobial therapy. Restart RINVOQ when infection is controlled following careful consideration of benefit risk.
- There is a higher incidence of infections in the elderly ≥ 65 years of age and in diabetics, caution should be used when treating these populations.
Tuberculosis
- Screen pre-treatment for TB. Do not start treatment in patients with active TB. Consult with a physician experienced in the treatment of TB and consider anti-TB therapy in those patients with previously untreated latent TB or patients with risk factors for TB infection
- Monitor for the development of signs and symptoms of TB, including those patients that tested negative for latent TB prior to treatment
Viral reactivation
- Consider interrupting treatment if patient develops herpes zoster until resolution
- Screen pre-treatment for viral hepatitis and monitor for reactivation during therapy. If hepatitis B DNA is detected during treatment consult a liver specialist
Vaccination
- It is not recommended to administer live attenuated vaccines during, or immediately prior to RINVOQ treatment
- It is recommended that patients are brought up-to-date with all immunisations including prophylactic zoster vaccination in agreement with current immunisation guidelines prior to starting RINVOQ
Malignancy
- There is a higher rate of malignancies with RINVOQ 30 mg compared to RINVOQ 15 mg
- In patients 65 years of age and older, patients who are current or past long-time smokers, or with other malignancy risk factors (e.g., current malignancy or history of malignancy) upadacitinib should only be used if no suitable treatment alternatives are available.
Non-melanoma skin cancer
- There is a higher rate of NMSC with RINVOQ 30 mg compared to RINVOQ 15 mg
- Periodically examine skin, particularly patients with risk factors for skin cancer
Haematologic abnormalities
- Screen pre-treatment for abnormalities
- Do not initiate RINVOQ and consider temporarily interrupting treatment if ANC <1 x 109 cells/L, ALC <0.5 x 109 cells/L or Hb <8g/dL
Major adverse cardiovascular events
- MACE events have been observed during RINVOQ treatment
- Patients 65 years of age and older, patients who are current or past long-time smokers, and patients with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors, upadacitinib should only be used if no suitable treatment alternatives are available
Lipids
- Monitor lipid levels at 12 weeks and thereafter according to clinical guidelines for hyperlipidaemia
Hepatic transaminase elevations
- Contraindicated in severe hepatic impairment
- Screen LFTs pre-treatment and monitor throughout therapy. Promptly investigate elevated LFTs to rule out drug induced liver injury. If increases in ALT or AST are observed during routine patient management and drug-induced liver injury is suspected, RINVOQ therapy should be interrupted until this diagnosis is excluded
Severe renal impairment
The recommended dose to be used with caution is:
- 15 mg in patients with RA, AS, PsA, nr-axSpA
Venous thromboembolism
- Use with caution in patients with risk factors for VTE
- Re-evaluate patient periodically to assess change in VTE risk
- Promptly evaluate any signs and symptoms of VTE and discontinue treatment if clinical signs of VTE occur and treat promptly
Diverticulitis
- Diverticulitis may cause gastrointestinal perforation
- Use with caution in patients with diverticular disease especially when treated with concomitant medications associated with an increase risk of diverticulitis: NSAIDs, corticosteroids and opioids
- Promptly evaluate new onset abdominal signs and symptoms for early identification
Allergic reaction
- Contraindicated in patients with known hypersensitivity to active substance or to any of its excipients
Pregnancy and lactation
- Contraindicated in pregnancy
- Women of childbearing potential should be advised to use effective contraception during treatment and for 4 weeks following the final dose of RINVOQ
- Should not be used during breastfeeding
Food and drink
- Should not consume food or drink containing grapefruit juice during treatment
Adverse reactions
Very common adverse reactions (≥1/10): Upper respiratory tract infections and acne. Common adverse reactions (≥1/100 to <1/10): Bronchitis, herpes zoster, herpes simplex, folliculitis, influenza, urinary tract infection, non-melanoma skin cancer, anaemia, neutropaenia, lymphopaenia, hypercholesterolaemia, hyperlipidaemia, cough, abdominal pain, nausea, urticaria, rash, fatigue, pyrexia, increased blood CPK/ALT/AST, increased weight and headache. Serious adverse reactions: The most common serious adverse events were serious infections
Please refer to Summary of Product Characteristics for complete product information.
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References
- RINVOQ SmPC.
- McInnes IB, Anderson J, Magrey M, et al. Efficacy and safety of upadacitinib versus placebo and adalimumab in patients active psoriatic arthritis and inadequate response to non-biologic disease-modifying antirheumatic drugs (SELECT-PsA 1): a double blind, randomized controlled phase 3 trial. Presented at: European Congress of Rheumatology Annual Meeting; June 3-6, 2020. Oral Presentation LB0001.
- Mease, et al. Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. Ann Rheum Dis. 2021;80:312-20.
- RINVOQ Product Safety Message.
UK-UPAD-230038. Date of preparation: March 2023
Adverse events should be reported. Reporting forms and information can be found at yellowcard.mhra.gov.uk.
Adverse events should also be reported to AbbVie on [email protected]
