Active Pharmacovigilance Study of the Medicine Rinvoq™ (Upadacitinib) (LOOK-UP)

The LOOK-UP is an investigator-initiated clinical study with the aim of monitoring the post-marketing safety of the medicine Rinvoq™ (upadacitinib), which is indicated for the treatment of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, ulcerative colitis, and Crohn's disease. The Marketing Authorisation Holder is AbbVie Deutschland GmbH & Co. KG.

Study Overview

• Status: Recruiting
• Conditions: Drug Use; Safety Issues; Adverse Drug Event; Inflammatory Disease; Adverse Drug Reaction; Drug Side Effect
• Intervention / Treatment: Drug: Upadacitinib

Detailed Description

The LOOK-UP study is an investigator-initiated clinical study conducted by INFARMED, the Portuguese Authority of Medicines and Health Products, I.P., and coordinated by the Porto Pharmacovigilance Centre at the Faculty of Medicine, University of Porto. The study aims to monitor the post-marketing safety of Rinvoq™ (upadacitinib), a medicine indicated for the treatment of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, ulcerative colitis, and Crohn's disease. Rinvoq™, a selective and reversible Janus Kinase (JAK) 1 inhibitor, has been under additional monitoring by the European Medicines Agency (EMA) since its approval in December 2019, necessitating active safety surveillance in real-world settings.

The primary objective of the LOOK-UP study is to quantify the incidence of adverse events in patients prescribed Rinvoq™, with a focus on serious adverse events such as malignant neoplasms, non-melanoma skin cancer, major adverse cardiovascular events, venous thromboembolism, serious and opportunistic infections, gastrointestinal perforations, liver injuries, bone fractures, and all-cause mortality. Secondary objectives include describing the incidence of adverse events among specific subgroups, such as very elderly patients, patients with moderate hepatic impairment, and patients with severe renal impairment. Additionally, the study aims to characterize patient-reported adverse events using MedDRA terms. An exploratory objective is to evaluate adherence to risk minimization measures recommended by the Pharmacovigilance Risk Assessment Committee (PRAC) for the safe use of Rinvoq™.

The study is designed as a Phase 4 post-authorization safety study (PASS), utilizing an observational cohort approach that is both multicentric and ambispective. This design includes prospective and retrospective monitoring of patients, ensuring comprehensive safety analysis. The study will be conducted exclusively in hospital settings within the Porto district, reflecting the prescription and usage constraints of Rinvoq™.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Inês Ribeiro Vaz, PharmD, MPH, PhD; Phone Number: + 351220426952; Email: inesvaz@med.up.pt
• Study Contact Backup: Name: Renato Ferreira da Silva, PharmD; Phone Number: +351220426913; Email: rsilva@med.up.pt

Study Locations

• Portugal
  • Porto, Portugal, 4050-366
    • Active, not recruiting
    • Unidade Local de Saude de Santo Antonio, E.P.E.
  • Porto, Portugal, 4200-319
    • Recruiting
    • Unidade Local de Saúde de São João, E.P.E.
    • Contact: Manuela Pinto, PharmD; Phone Number: +351225512143; Email: manuela.milne@ulssjoao.min-saud.pt
    • Principal Investigator: Manuela Pinto, PharmD
  • Porto, Portugal, 4434-502
    • Active, not recruiting
    • Unidade Local de Saude de Gaia/Espinho, E.P.E.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients exposed to upadacitinib (Rinvoq™).

Description

Inclusion Criteria:

• Prescription of Rinvoq™ from January 1, 2024;
• 18 years of age or older at the time of recruitment; and
• Expressed consent to participate in the study.

Exclusion Criteria:

• They have any degree of cognitive impairment that prevents them from responding to a questionnaire administered by telephone;
• They are participating in a phase I, II, or III clinical trial;
• They have a life expectancy of less than 1 month; or
• They do not have a valid telephone contact.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Upadatacinib Arm; Patients exposed to upadacitinib (Rinvoq™)	Drug: Upadacitinib; Exposure to upadacitinib (Rinvoq™) in its different formulations approved by the Portuguese regulatory authority (15, 30, or 45mg extended-release tablets).; Other Names: Rinvoq; ATC 200000041628

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Incidence of adverse events occurring during the established follow-up period, coded according to MedDRA terminology. The outcome will be assessed through an ad-hoc questionnaire. The occurrence of adverse events will be queried in an open-ended, non-directed manner. Patients will be encouraged to report any undesired events they experience during the treatment, without being limited to predefined specific adverse events.	For the prospective cohort, the follow-up includes contacts at baseline (t=0), 2 weeks (t=1), 1 month (t=2), 2 months (t=3), and 3 months (t=4) after starting treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of non-compliance with PRAC recommendations	Rate at which patients identified with risk factors are prescribed Rinvoq™ despite the availability of viable therapeutic alternatives. Patients considered to have risk factors include: (i) individuals aged 65 or older; (ii) current smokers or those with a long history of smoking; (iii) individuals at high risk of serious cardiovascular problems, such as heart attacks or strokes, or those more likely to develop cancer. The outcome will be assessed through direct contact with clinical specialists (prescribers) to confirm the availability of therapeutic alternatives. A case is non-compliant if a patient with risk factors is prescribed Rinvoq™ despite an available alternative.	This outcome will be assessed at any time during the three-month monitoring period of each patient.

Collaborators and Investigators

• Sponsor: Universidade do Porto
• Collaborators: INFARMED - Autoridade Nacional do Medicamento e Produtos de Saúde, I.P.; Unidade de Farmacovigilância do Porto; Unidade Local de Saúde de São João, E.P.E.; Unidade Local de Saúde de Santo António, E.P.E.; Unidade Local de Saúde de Gaia/Espinho, E.P.E.; RISE Health
• Investigators: Principal Investigator: Inês Ribeiro Vaz, PharmD, MPH, PhD, Universidade do Porto

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2024
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 4, 2024
• First Submitted That Met QC Criteria: July 4, 2024
• First Posted (Actual): July 12, 2024

Study Record Updates

• Last Update Posted (Actual): July 15, 2024
• Last Update Submitted That Met QC Criteria: July 12, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Patient Safety; Upadacitinib; Crohn's disease; Atopic dermatitis; Ulcerative colitis; Psoriatic arthritis; Rheumatoid arthritis; Axial spondyloarthritis; Rinvoq; Pharmacovigilance risk; Drug safety monitoring
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Janus Kinase Inhibitors; Upadacitinib
• Other Study ID Numbers: LookUp; EUPAS1000000227 (Other Identifier: European Medicines Agency)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No