Upadacitinib for Psoriatic Arthritis

(UP-SPOUT Trial)

Recruiting at 3 trial locations

Overseen By Rana Dadashova

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: CARE ARTHRITIS LTD.

Must not be taking: JAK-inhibitors, TYK2-inhibitors

Disqualifiers: Active infection, Tuberculosis, Hepatitis, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

100 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of certain medications like NSAIDs, mild opioids, oral corticosteroids, topical therapies, and some csDMARDs for a specified period before starting the study. If you are on bioDMARD therapy, a washout period (time without taking the medication) is required before the screening MRI, but you should not stop a successful biological therapy just to join the study.

What data supports the effectiveness of the drug Upadacitinib for treating psoriatic arthritis?

Research shows that Upadacitinib helps improve symptoms and quality of life for people with psoriatic arthritis, especially those who haven't responded well to other treatments. Studies found it reduces pain and improves patient-reported outcomes compared to a placebo or other drugs like adalimumab. ^{1 2 3 4 5}

Is upadacitinib safe for humans?

Upadacitinib has been studied for safety in conditions like rheumatoid arthritis, psoriatic arthritis, and atopic dermatitis, with data showing it is generally safe for long-term use, though some adverse events have been reported. It is important to discuss potential risks with a healthcare provider. ^{1 6 7 8 9}

How is the drug Upadacitinib different from other treatments for psoriatic arthritis?

Upadacitinib is unique because it is an oral Janus kinase inhibitor, which works by blocking specific enzymes involved in the inflammatory process, and is effective for patients who have not responded well to biologic treatments. This makes it a novel option for those with psoriatic arthritis who have had inadequate responses to other therapies. ^{1 10 11 12 13}

What is the purpose of this trial?

A Randomized, Placebo-controlled, Multicenter, Study to Evaluate the Impact of Upadacitinib on Spondyloarthritis Outcomes in Patients with Active Psoriatic Arthritis (UP-SPOUT)

Research Team

Walter Maksymowych, Dr.

Principal Investigator

CARE ARTHRITIS LTD.

Eligibility Criteria

Adults with active psoriatic arthritis, evidence of axial involvement, and chronic back pain may join. They must have tried NSAIDs without success or cannot take them due to intolerance. Participants need a history or current signs of psoriasis, no rheumatoid factor, possible nail changes or dactylitis, and radiologic signs of bone formation near joints.

Inclusion Criteria

Evidence of axial involvement demonstrated by previous imaging techniques

I understand and agree to follow the study rules and will sign the consent form.

Classification of PsA according to CASPAR criteria with specific criteria points

Exclusion Criteria

History of certain autoimmune diseases or inflammatory conditions

I do not have any current infections needing treatment.

I have or might have COVID-19.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Upadacitinib or placebo tablets once per day

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Upadacitinib

Trial Overview The UP-SPOUT trial is testing Upadacitinib (Rinvoq), comparing it against a placebo in people with active psoriatic arthritis to see its effects on spondyloarthritis outcomes. It's randomized and controlled; participants won't know if they're getting the real drug or a dummy pill.

Participant Groups

Group I: Upadacitinib Experimental Treatment 1 Intervention

Participants randomized to this arm will receive Upadacitinib 15 mg tablets, once per day, for 12 weeks.

Group II: Placebo Placebo Group 1 Intervention

Participants randomized to this arm will receive matching placebo tablets with no active ingredients, once per day, for 12 weeks.

Who Is Running the Clinical Trial?

CARE ARTHRITIS LTD.

Lead Sponsor

Trials

3

Recruited

730+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Findings from Research

In a study of 296 patients with active psoriatic arthritis, upadacitinib significantly improved disease activity, with the proportion of patients achieving minimal disease activity rising from 2.7% at baseline to 39.1% by week 24.

The safety profile of upadacitinib remained consistent with previous studies, showing no new safety risks, indicating it is a safe and effective treatment option for patients with psoriatic arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with Upadacitinib in Active Psoriatic Arthritis: Efficacy and Safety Data of the First 192 Patients from the UPJOINT Study, a Multicentre, Observational Study in Clinical Practice. Werner, SG., Baraliakos, X., Reckert, S., et al.[2023]

In a phase 3 trial involving patients with psoriatic arthritis who did not respond to previous treatments, upadacitinib showed significant improvements in patient-reported outcomes (PROs) compared to placebo and was as effective as adalimumab, particularly in measures like the Health Assessment Questionnaire Disability Index (HAQ-DI) and the SF-36 Physical Component Summary score.

Patients treated with upadacitinib experienced rapid improvements in symptoms as early as week 2, with sustained benefits observed through week 56, indicating its efficacy in enhancing quality of life for those with psoriatic arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement in Patient-Reported Outcomes in Patients with Psoriatic Arthritis Treated with Upadacitinib Versus Placebo or Adalimumab: Results from SELECT-PsA 1. Strand, V., Mease, PJ., Soriano, ER., et al.[2022]

In three randomized trials involving patients with active psoriatic arthritis (PsA) and ankylosing spondylitis (AS), upadacitinib demonstrated significant pain relief, with a higher percentage of patients achieving at least a 30%, 50%, or 70% reduction in pain compared to placebo as early as week 2, and these improvements were sustained over one year.

Patients who switched from placebo to upadacitinib were able to achieve similar pain relief levels as those who continuously received upadacitinib, indicating its effectiveness even for those who initially did not respond to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: post hoc analysis of three randomised clinical trials. McInnes, IB., Ostor, AJK., Mease, PJ., et al.[2022]

In the phase 3 SELECT-PsA 2 trial involving patients with psoriatic arthritis who had inadequate responses to biologic treatments, upadacitinib significantly improved patient-reported outcomes (PROs) such as pain, physical function, and quality of life at weeks 12 and 24 compared to placebo.

Improvements in PROs were not only statistically significant but also clinically meaningful, with many patients experiencing benefits as early as week 2, and these improvements were maintained or enhanced through week 56.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes in Psoriatic Arthritis Patients with an Inadequate Response to Biologic Disease-Modifying Antirheumatic Drugs: SELECT-PsA 2. Strand, V., Van den Bosch, F., Ranza, R., et al.[2022]

Upadacitinib demonstrated sustained efficacy in patients with psoriatic arthritis (PsA) over 152 weeks, maintaining improvements in key clinical outcomes such as the American College of Rheumatology criteria and the Psoriasis Area and Severity Index.

The long-term safety profile of upadacitinib was favorable, with no new safety concerns identified, indicating it was well tolerated in this population with inadequate response to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib in patients with psoriatic arthritis and inadequate response to biologics: 3-year results from the open-label extension of the randomised controlled phase 3 SELECT-PsA 2 study. Mease, P., Setty, A., Papp, K., et al.[2023]

A total of 4,494 adverse event reports associated with upadacitinib were identified from over 3.8 million reports in the FDA database, indicating a significant number of potential safety concerns.

The study revealed unexpected adverse events such as arthralgia, musculoskeletal stiffness, diverticulitis, and cataracts, with most adverse events occurring within the first four months of treatment, highlighting the need for careful clinical monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Safety Concerns with Upadacitinib: A Disproportionality Analysis of the FDA Adverse Event Reporting system. Wu, XP., Lu, XK., Wang, ZT., et al.[2023]

Upadacitinib has been evaluated for long-term safety in 6991 patients across various conditions, showing that it is generally well tolerated with similar rates of treatment-emergent adverse events (TEAEs) across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and atopic dermatitis.

While the overall safety profile is favorable, certain risks such as herpes zoster and non-melanoma skin cancer were higher in patients with rheumatoid arthritis and psoriatic arthritis compared to active comparators, indicating the need for careful monitoring in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. Burmester, GR., Cohen, SB., Winthrop, KL., et al.[2023]

Upadacitinib, an oral Janus kinase inhibitor, demonstrated a safety profile similar to adalimumab in patients with active psoriatic arthritis over a treatment period of up to 3 years, with no new safety risks identified during long-term exposure.

While the overall rates of serious adverse events like malignancies and major cardiovascular events were comparable between upadacitinib and adalimumab, upadacitinib was associated with higher rates of herpes zoster and opportunistic infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials. Burmester, GR., Winthrop, K., Blanco, R., et al.[2022]

In a post-hoc analysis of two clinical trials involving patients with psoriatic arthritis (PsA), those with axial involvement showed significantly greater improvements in disease activity scores (BASDAI and ASDAS) when treated with upadacitinib (UPA15) compared to placebo and adalimumab (ADA).

The safety profile of upadacitinib was consistent across patients with and without axial involvement, indicating that it is a safe treatment option for PsA patients regardless of their axial symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of upadacitinib in patients with active psoriatic arthritis and axial involvement: results from two phase 3 studies. Baraliakos, X., Ranza, R., Östör, A., et al.[2023]

In a 24-week phase 3 trial with 1704 patients, upadacitinib (both 15 mg and 30 mg doses) significantly improved ACR20 response rates compared to placebo, indicating its efficacy in treating psoriatic arthritis.

The 30 mg dose of upadacitinib was found to be superior to adalimumab, while both doses were noninferior, suggesting that upadacitinib could be a more effective option for patients who do not respond adequately to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial of Upadacitinib and Adalimumab for Psoriatic Arthritis. McInnes, IB., Anderson, JK., Magrey, M., et al.[2021]

In a 56-week study involving 641 patients with psoriatic arthritis who had not responded well to biologic therapy, upadacitinib demonstrated sustained efficacy in improving symptoms, as measured by ACR and PASI criteria.

The safety profile of upadacitinib was acceptable, with serious infections occurring at a low rate, although there was a higher incidence of non-serious herpes zoster in patients taking the higher dose of 30 mg.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib in Patients with Psoriatic Arthritis and Inadequate Response to Biologics: 56-Week Data from the Randomized Controlled Phase 3 SELECT-PsA 2 Study. Mease, PJ., Lertratanakul, A., Papp, KA., et al.[2021]

In a 24-week phase 3 trial involving 642 patients with psoriatic arthritis who had previously not responded to biologic DMARDs, upadacitinib at doses of 15 mg and 30 mg significantly improved symptoms compared to placebo, with ACR20 response rates of 56.9% and 63.8% respectively versus 24.1% for placebo.

At week 24, a higher percentage of patients treated with upadacitinib achieved minimal disease activity (MDA) compared to placebo (25.1% for 15 mg and 28.9% for 30 mg versus 2.8% for placebo), indicating its efficacy in managing psoriatic arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. Mease, PJ., Lertratanakul, A., Anderson, JK., et al.[2022]

Upadacitinib, an oral Janus kinase inhibitor, has demonstrated robust efficacy in treating psoriatic arthritis (PsA) in two global phase III studies involving 1916 patients, with efficacy endpoints improving as plasma concentrations of the drug increased.

The 15 mg daily dosage of upadacitinib is predicted to provide effective treatment for PsA while maintaining a favorable safety profile, showing limited incidences of serious infections and significant reductions in hemoglobin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upadacitinib pharmacokinetics and exposure-response analyses of efficacy and safety in psoriatic arthritis patients - Analyses of phase III clinical trials. Muensterman, E., Engelhardt, B., Gopalakrishnan, S., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Treatment with Upadacitinib in Active Psoriatic Arthritis: Efficacy and Safety Data of the First 192 Patients from the UPJOINT Study, a Multicentre, Observational Study in Clinical Practice. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Improvement in Patient-Reported Outcomes in Patients with Psoriatic Arthritis Treated with Upadacitinib Versus Placebo or Adalimumab: Results from SELECT-PsA 1. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Effect of upadacitinib on reducing pain in patients with active psoriatic arthritis or ankylosing spondylitis: post hoc analysis of three randomised clinical trials. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes in Psoriatic Arthritis Patients with an Inadequate Response to Biologic Disease-Modifying Antirheumatic Drugs: SELECT-PsA 2. [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

Upadacitinib in patients with psoriatic arthritis and inadequate response to biologics: 3-year results from the open-label extension of the randomised controlled phase 3 SELECT-PsA 2 study. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Post-Marketing Safety Concerns with Upadacitinib: A Disproportionality Analysis of the FDA Adverse Event Reporting system. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Safety Profile of Upadacitinib up to 3 Years in Psoriatic Arthritis: An Integrated Analysis of Two Pivotal Phase 3 Trials. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of upadacitinib in patients with active psoriatic arthritis and axial involvement: results from two phase 3 studies. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Trial of Upadacitinib and Adalimumab for Psoriatic Arthritis. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Upadacitinib in Patients with Psoriatic Arthritis and Inadequate Response to Biologics: 56-Week Data from the Randomized Controlled Phase 3 SELECT-PsA 2 Study. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Upadacitinib pharmacokinetics and exposure-response analyses of efficacy and safety in psoriatic arthritis patients - Analyses of phase III clinical trials. [2022]