An Observational Study to Evaluate Impact of CRP-Level on Real World Effectiveness of Upadacitinib as Monotherapy or in Combination With MTX in Adult Participants With Rheumatoid Arthritis (UPWARDS)

UPwArds - Post Marketing Observational Study to Evaluate the Impact of CRP-Level on the Real World Effectiveness of UPadacitinib When Used in MonotherApy or in Combination With MTX in Patients With RheumatoiD ArthritiS

Rheumatoid Arthritis (RA) is a chronic inflammatory disease causing pain, stiffness, swelling and loss of joint function. RA can reduce the ability to perform everyday tasks. This study assesses whether C-reactive protein (CRP)-level has an impact on achieving remission with upadacitinib when used alone or in combination with methotrexate (MTX). This study will also assess the reduction in pain, morning stiffness, fatigue, functionality, health status and impact of RA.

CRP is an indicator of inflammation and often used for disease activity monitoring during RA treatment. Upadacitinib is a Janus kinase (JAK) inhibitor indicated for the treatment of adults with moderately to severely active RA who have had an inadequate response or intolerance to methotrexate. This study has two groups - upadacitinib monotherapy and combination. Adult participants with moderate to severe RA will be enrolled. Around 500 participants will be enrolled in the study in multiple sites within Germany.

Participants will receive upadacitinib alone or in combination with MTX per their physicians' usual prescription. Individual data will be collected for 12 months.

No additional study-related tests will be conducted during the routine physician visits. Only data which are routinely collected during a regular visit will be utilized for this study.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis (RA)

• Study Type: Observational
• Enrollment (Actual): 534

Contacts and Locations

Study Locations

• Germany
  • Altenburg, Germany, 04600
    • Kupka & Kupka, Altenburg, DE /ID# 218413
  • Amberg, Germany, 92224
    • Marycz, Amberg, DE /ID# 220808
  • Augsburg, Germany, 86157
    • Rheumapraxis am Webereck /ID# 218712
  • Bad Pyrmont, Germany, 31812
    • MVZ Weserbergland /ID# 220809
  • Bayreuth, Germany, 95444
    • Internistische-rheumatologische Praxisgemeinschaft /ID# 218540
  • Berlin, Germany, 10713
    • Bozorg-Doagoo, Berlin, DE /ID# 218431
  • Berlin, Germany, 13055
    • Praxis Dr. Silke Zinke /ID# 218433
  • Braunschweig, Germany, 38100
    • Eisterhues, Braunschweig, DE /ID# 218532
  • Burghausen, Germany, 84489
    • Medizinische Versorgungszentren Burghausen Altoetting /ID# 221385
  • Chemnitz, Germany, 09130
    • Med Versorgungszentrum AGILOMED /ID# 218538
  • Coburg, Germany, 96450
    • Dres. Schuh /ID# 218541
  • Dresden, Germany, 01109
    • Rheumatologisches MVZ Dresden /ID# 218411
  • Duesseldorf, Germany, 40211
    • Strothmeyer & Scheulen /ID# 218426
  • Düren, Germany, 52355
    • Rheumapraxis Düren /ID# 224950
  • Ehringshausen, Germany, 35630
    • Praxis Dilltal /ID# 218427
  • Erlangen, Germany, 91056
    • Praxisgemeinschaft Rheumatologie Nephrologie Erlangen /ID# 222579
  • Essen, Germany, 45326
    • Dres. Waehrisch/Flaxenberg /ID# 218711
  • Freiberg, Germany, 09599
    • Michael Mueller, Freiberg, DE /ID# 218414
  • Haldensleben, Germany, 39340
    • Praxis Dr. Kuehne /ID# 221389
  • Halle, Germany, 06128
    • Praxis Dr. Liebhaber /ID# 218899
  • Hamburg, Germany, 22767
    • Aries, Hamburg, DE /ID# 220804
  • Hannover, Germany, 30161
    • Stille, Hanover, DE /ID# 218429
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover /ID# 222068
  • Heidelberg, Germany, 69120
    • Heilig, Heidelberg, DE /ID# 221391
  • Hoppegarten, Germany, 15366
    • Praxis K. Pagel /ID# 218714
  • Leipzig, Germany, 04109
    • Hamann & Teich & Boche,Leipzig /ID# 218531
  • Leipzig, Germany, 04129
    • Schwarze/Haeder, Leipzig, DE /ID# 218412
  • Leverkusen, Germany, 51373
    • Dres. Teipel/Toussaint/Saech /ID# 223969
  • Magdeburg, Germany, 39104
    • Aurich & Sieburg, Magdeburg /ID# 220811
  • Marktredwitz, Germany, 95615
    • Harmuth, Marktredwitz, DE /ID# 218715
  • Munich, Germany, 80935
    • Prof-med-stud.de /ID# 218534
  • Neubrandenburg, Germany, 17033
    • Praxis Dr. med Thilo Klopsch /ID# 218535
  • Nienburg, Germany, 31582
    • Praxis Hein & Gess /ID# 218716
  • Nienburg, Germany, 31582
    • Praxis Hein & Gess /ID# 218896
  • Olsberg, Germany, 59939
    • Elisabeth-Klinik Bigge /ID# 218425
  • Planegg, Germany, 82152
    • MVZ für Rheumatologie Dr. M. Welcker GmbH /ID# 218543
  • Puettlingen, Germany, 66346
    • Knappschaftsklinikum Saar /ID# 218901
  • Ratingen, Germany, 40882
    • Rheumazentrum Ratingen /ID# 218897
  • Schwerin, Germany, 19053
    • Rheumatologische Gemeinschaftspraxis Schwerin /ID# 218432
  • Seesen, Germany, 38723
    • Melzer, Seesen, DE /ID# 220803
  • Stuttgart, Germany, 70372
    • Rheumatologische Schwerpunktpraxis /ID# 218415
  • Trier, Germany, 54292
    • Bruederkrankenhaus Trier /ID# 221393
  • Tuebingen, Germany, 72072
    • Praxis Dr. Haas /ID# 218423
  • Ulm, Germany, 89073
    • Rheumathologie Ulm /ID# 218539
  • Wuppertal, Germany, 42105
    • Krankenhaus St. Josef /ID# 221392
  • Wuppertal, Germany, 42285
    • Praxis Barmen /ID# 218895
  • Zwickau, Germany, 08060
    • Fricke-Wagner, Zwickau, DE /ID# 218533
  • Baden-Wuerttemberg
    • Ulm, Baden-Wuerttemberg, Germany, 89073
      • Praxis Dr. Rinaldi /ID# 218424
  • Bayern
    • Munich, Bayern, Germany, 81541
      • Praxis Dres. Kellerer/Kellerer/Krüger /ID# 218428
  • Brandenburg
    • Potsdam, Brandenburg, Germany, 14467
      • Rheumahaus Studien GbR, Potsdam, DE /ID# 218430
  • Nordrhein-Westfalen
    • Herne, Nordrhein-Westfalen, Germany, 44649
      • Rheumazentrum Ruhrgebiet /ID# 221388
  • Sachsen
    • Dresden, Sachsen, Germany, 01097
      • Praxis Dr. Lüthke /ID# 218900

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult Participants with moderate to severe rheumatoid arthritis (RA)

Description

Inclusion Criteria:

• Diagnosis of moderate to severe active rheumatoid arthritis (RA) upon judgment of the treating physician.
• Swollen Joint Count (SJC) >= 3 of 28 joints of the Disease Activity Score (DAS)28.
• Measurement of C-Reactive Protein (CRP)-level at Baseline (BL) or <= 4 weeks prior to BL at a timepoint when the Prednisolone equivalent dose of Glucocorticoid treatment was <= 10 mg/day for at least 7 days.
• Upadacitinib treatment is indicated as per local Summary of Product characteristics (SmPC).
• Decision on the treatment with Upadacitinib was made prior to any decision to approach the patient to participate in this study.

Exclusion Criteria:

• Participants who cannot be treated with Upadacitinib according to the local Upadacitinib SmPC.
• Prior treatment with Upadacitinib.
• Treatment with Sarilumab or Tocilizumab within the last 8 weeks before the CRP level for inclusion was measured.
• Participants currently participating in interventional research.
• Participants who are unwilling or unable to complete the patient reported questionnaires.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Participants treated with upadacitinib monotherapy; Participants will receive upadacitinib for 12 months as prescribed by the physician
Participants treated with upadacitinib in combination with MTX; Participants will receive upadacitinib in combination with MTX as prescribed by the physician for 12 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Remission	Remission is defined as clinical disease activity index (CDAI) <=2.8	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Remission	Remission is defined as the disease activity score at 28 joints (DAS28)-C-Reactive protein (CRP)<2.6, DAS28- erythrocyte sedimentation rate (ESR)<2.6, simplified disease activity index (SDAI)<=3.3, CDAI<=2.8, Boolean.	Up to 12 Months
Percentage of Participants Achieving Low Disease Activity (LDA)	LDA is defined as DAS28-CRP<3.2, DAS28-ESR<3.2, SDAI <=11, CDAI<=10	Up to 12 Months
Mean Change From Baseline in CDAI	The CDAI is a validated measure of RA disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global health assessed by the participant on a visual analogue scale (VAS) from 0 to 10 (cm), and global health assessed by an investigator on a visual analogue scale from 0 to 10 (cm) were included in the CDAI score. Scores on the CDAI range from 0 (lowest disease activity) to 76 (highest disease activity).	Up to 12 Months
Mean Change From Baseline in SDAI	The SDAI is a validated measure of RA disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, global disease activity assessed by the participant on a visual analogue scale from 0 to 10 (cm) , global disease activity assessed by an investigator on a visual analogue scale from 0 to 10 (cm), and serum levels of C-reactive protein (mg/dL) were included in the SDAI score. Scores on the SDAI range from 0 (lowest disease activity) to 86 (highest disease activity).	Up to 12 Months
Mean Change From Baseline in DAS28-CRP	The Disease Activity Score (DAS) 28 is a validated index of rheumatoid arthritis disease activity. Scores on the DAS28 range from 0 (lowest disease activity) to 10 (highest disease activity).	Up to 12 Months
Mean Change From Baseline in DAS28-ESR	The Disease Activity Score (DAS) 28 is a validated index of rheumatoid arthritis disease activity. Scores on the DAS28 range from 0 (lowest disease activity) to 10 (highest disease activity).	Up to 12 Months
Percentage of Participants Achieving Pain Reduction (Improvement by 30 %)	Improvement in pain reduction is assessed by numeric rating scale (NRS). The NRS of Pain sheet will be filled out in the office by participants at the designated visits.	Up to 12 Months
Percentage of Participants Achieving Pain Reduction (Improvement by 50 %)	Improvement in pain reduction is assessed by numeric rating scale (NRS). The NRS of Pain sheet will be filled out in the office by participants at the designated visits.	Up to 12 Months
Percentage of Participants Achieving Pain Reduction (Improvement by 70 %)	Improvement in pain reduction is assessed by numeric rating scale (NRS). The NRS of Pain sheet will be filled out in the office by participants at the designated visits.	Up to 12 Months
Mean Change From Baseline in Pain	The NRS of Pain sheet will be filled out in the office by participants at the designated visits.	Up to 12 Months
Percentage of Participants Achieving Fatigue Reduction (Improvement by 30 %)	Improvement in fatigue reduction is assessed by numeric rating scale (NRS). The NRS of fatigue sheet will be filled out in the office by participants at the designated visits.	Up to 12 Months
Percentage of Participants Achieving Fatigue Reduction (Improvement by 50 %)	Improvement in fatigue reduction is assessed by numeric rating scale (NRS). The NRS of fatigue sheet will be filled out in the office by participants at the designated visits.	Up to 12 Months
Percentage of Participants Achieving Fatigue Reduction (Improvement by 70 %)	Improvement in fatigue reduction is assessed by numeric rating scale (NRS). The NRS of fatigue sheet will be filled out in the office by participants at the designated visits.	Up to 12 Months
Mean Change From Baseline in Fatigue	Change in Fatigue is assessed by numeric rating scale (NRS). The NRS of fatigue sheet will be filled out in the office by participants at the designated visits.	Up to 12 Months
Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID)	RAID is a tool for assessment of disease activity purely based on a patient questionnaire.	Up to 12 Months
Percentage of Participants Achieving RAID <= 3	RAID is a tool for assessment of disease activity purely based on a patient questionnaire.	Up to 12 Months
Percentage of Participants Achieving RAID > 3 and <=4	RAID is a tool for assessment of disease activity purely based on a patient questionnaire.	Up to 12 Months
Percentage of Participants Achieving RAID > 4 and <=6	RAID is a tool for assessment of disease activity purely based on a patient questionnaire.	Up to 12 Months
Percentage of Participants Achieving RAID > 6	RAID is a tool for assessment of disease activity purely based on a patient questionnaire.	Up to 12 Months
Change From Baseline in Morning Stiffness Severity	Morning stiffness severity was assessed by a numeric rating-scale (NRS). Participants rated the severity of morning stiffness during the past week from 0 to 10 with 0 representing "not severe" and 10 "very severe".	Up to 12 Months
Change From Baseline in Morning Stiffness Duration	The duration of morning stiffness was reported by participants as the average daily length during the past week in minutes (from time of awaking to time of maximal improvement).	Up to 12 Months
Change From Baseline in Functionality (FFbH)	A self-administered patient questionnaire used to assess patient function based on 18 questions. The numerically coded responses to the questions are added to provide a total patient score.	Up to 12 Months
Change From Baseline in Patient Health Questionnaire (PHQ-9)	The PHQ-9 is a 9-item questionnaire for assessing the severity of depression. Each question is answered on a scale from 0 (not at all) to 3 (nearly every day). The total score ranges from 0 to 27, where higher scores indicate more severe depression.	Up to 12 Months
Percentage of Participants With Minimal Clinically Important Difference (MCID) in PHQ-9	MCID is defined as the at least 5 points difference from baseline in PHQ-9. The PHQ-9 is a 9-item questionnaire for assessing the severity of depression.	Up to 12 Months
Percentage of Participants With Low Disease Activity (LDA) or Remission Without Actual Concomitant MTX	LDA is defined as DAS28 < 3.2, CDAI<=10, SDAI <11. Remission is defined as DAS28<2.6, CDAI<=2.8; Boolean Remission.	Up to 12 Months
Percentage of Participants With LDA or Remission With Actual Concomitant MTX	LDA is defined as DAS28 < 3.2, CDAI<=10, SDAI <11. Remission is defined as DAS28<2.6, CDAI<=2.8; Boolean Remission.	Up to 12 Months

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

Helpful Links

• clinical study report synopsis

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2020
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): February 1, 2022

Study Registration Dates

• First Submitted: February 11, 2020
• First Submitted That Met QC Criteria: February 11, 2020
• First Posted (Actual): February 13, 2020

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Upadacitinib; C-reactive protein (CRP); Rheumatoid Arthritis (RA); RINVOQ; ABT-494; Methotrexate (MTX)
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: P20-078

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No