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RINVOQ's safety profile demonstrated out to 4.5 years, across Phase III trials involving 4,400 patients and more than 7,000 patient-years of exposure2

Integrated safety analysis of RINVOQ up to 4.5 years of exposure*2

Data from 6 randomised, double-blind, controlled Phase III RINVOQ trials (SELECT-EARLY, SELECT-NEXT, SELECT-MONOTHERAPY, SELECT-COMPARE, SELECT-BEYOND and SELECT-CHOICE) were analysed.2

*Patients who switched from placebo, adalimumab or MTX to RINVOQ were included in the RINVOQ analysis set from the start of RINVOQ, while those who switched from RINVOQ to adalimumab (SELECT-COMPARE) were included in the adalimumab analysis set from the start of adalimumab. MTX monotherapy was censored at the time of rescue to combination therapy (addition of RINVOQ).

#Most cases of herpes zoster were non-serious and single dermatome. MACE defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. VTE defined as deep vein thrombosis and pulmonary embolism. §Deaths including non-treatment-emergent deaths. There were 27, 4 and 1 treatment-emergent deaths in patients receiving RINVOQ 15 mg OD, adalimumab 40 mg EOW + MTX and MTX monotherapy, respectively. SMR analysis, using World Health Organization data to estimate the number of expected deaths, demonstrated that the number of deaths in patients exposed to RINVOQ 15 mg OD was not higher than what would be expected for the general population. The most frequent treatment-emergent adverse events (≥5 Events/100 PYs) in RINVOQ-treated patients were upper respiratory tract infection, nasopharyngitis, urinary tract infection, bronchitis, increased creatine phosphokinase, increased alanine aminotransferase, worsening RA and herpes zoster.2

AE = adverse event; MACE = major adverse cardiovascular event; MTX = methotrexate; NMSC = non-melanoma skin cancer; PYs = patient years; OD = once-daily; SAE =  serious adverse event; VTE = venous thromboembolism.

Treatment emergent AEs of special interest in patients treated with RINVOQ + MTX or adalimumab + MTX*2

Graph adapted from source material.

*ADA 40 mg EOW: n=579, PY=1051.8; RIN 15 mg OD pooled; n=3209, PY=7023.8

Patients who switched from placebo, adalimumab or MTX to RINVOQ were included in the RINVOQ analysis set from the start of RINVOQ, while those who switched from RINVOQ to adalimumab (SELECT-COMPARE) were included in the adalimumab analysis set from the start of adalimumab.

#Most cases of herpes zoster were non-serious and single dermatome.

MACE defined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke.

VTE defined as deep vein thrombosis and pulmonary embolism.

The safety profile of RINVOQ monotherapy was similar to that reported in other RINVOQ trials4

Safety analysis of RINVOQ 15mg monotherapy at Week 144

No new safety signals were reported at Week 845

  • The most frequently reported TEAEs in patients receiving  RINVOQ 15 mg monotherapy (≥5 events /100 PY) were urinary tract infection, CPK increase, upper respiratory tract infection, nasopharyngitis, worsening of RA, bronchitis, herpes zoster, and alanine aminotransferase increase5

Table adapted from source material.  

*MTX: urosepsis; RINVOQ 15 mg: limb abscess. 

MTX: fungal oesophagitis. 

Except for 1 case of mild hepatic cyst in the RINVOQ 15 mg arm, all due to liver enzyme elevation. 

§MTX: basal cell carcinoma; RINVOQ 15: 1 non-Hodgkin lymphoma, 1 breast cancer. 

Pulmonary embolism (in a patient on oestrogen hormone with a body-mass index of 44.9); investigator deemed as unrelated to study drug.

||RINVOQ 15: 1 haemorrhagic stroke due to ruptured aneurysm (fatal); investigator deemed as unrelated to study drug.

**Haemorrhagic stroke due to ruptured aneurysm.3

Summary of the RINVOQ safety profile

The most commonly reported adverse reactions with RINVOQ 15 mg were upper respiratory tract infections, blood creatine 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

*Presented as grouped term.

In atopic dermatitis trials, the frequency of bronchitis, hypercholesterolaemia, ALT increased, and AST increased was uncommon.

In rheumatologic disease trials, the frequency was common for acne and uncommon for urticaria.

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.

Contraindications

  • Patient has a hypersensitivity to the active substance or to any of the excipients
  • Patient has active tuberculosis (TB) or an active, serious infection, including localised infections, or develops a serious or opportunistic infection
  • Patient is pregnant
  • Patient has severe hepatic impairment (Child Pugh C)

Monitoring requirements

Treatment with RINVOQ should not be initiated, or should be interrupted if:1

  • Absolute neutrophil count <1 x 109 cells/L3*
  • Absolute lymphocyte count <0.5 x 109 cells/L3*
  • Haemoglobin <8 g/dL
  • Drug-induced liver injury is suspected
  • Patient develops a serious or opportunistic infection
  • A patient with an infection who 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 (Child-Pugh C) 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 ≥3 x ULN in at least one measurement were observed in 0.8% and 0.4% of patients treated with RINVOQ 15 mg, 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 15 mg treatment was associated with 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 15 mg 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.

Safety Information3

Important safety information for RINVOQ

Before starting RINVOQ treatment, please note the following:

  1. RINVOQ should be initiated and supervised by physicians experienced in the treatment of rheumatoid arthritis
  2. Treatment should not be initiated in patients with an absolute lymphocyte count (ALC) <0.5 x 109 cells/L, absolute neutrophil count (ANC) <1 x 109 cells/L or Hb <8 g/dL

 

Concomitant use with other potent immunosuppressants

  • Not recommended, as a risk of additive immunosuppression cannot be excluded

 

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, caution should be used when treating this population

 

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

  • Immunological medicinal products may increase the risk of malignancies. In RA patients the risk of malignancies, including lymphoma is increased. Consider the risk benefit prior to initiating RINVOQ

 

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

 

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

  • Use 15mg with caution in patients with severe renal impairment

 

VTE

  • Use with caution in patient at high risk of DVT/PE and discontinue treatment if clinical signs of DVT/PE 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

 

Cardiovascular

  • Manage patients with known cardiovascular risk factors e.g. hypertension, hyperlipidaemia as part of usual standard of care

 

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 (across all RINVOQ indications)

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, follilculitis, influenza, urinary tract infection, 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.

 

References

  1. RINVOQ SmPC.
  2. Cohen SB, van Vollenhoven R, Curtis JR, et al. 2021 EULAR E-Congress; POS0220.
  3. RINVOQ Product Safety Message.
  4. Smolen JS, Pangan AL, Emery P, et al. Lancet. 2019;393:2303-11.
  5. Smolen JS, Emery P, Rigby W, et al. Eur Congress Rheumatol, 3-6 June, 2020; THU0213.

UK-UPAD-220198. Date of preparation: August 2022.

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 GBPV@abbvie.com