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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called upadacitinib, a Janus kinase inhibitor, to evaluate its effectiveness for people with active psoriatic arthritis, which causes painful joint swelling, particularly in the spine. Participants will be divided into two groups: one receiving the medication and the other a placebo (a pill with no active ingredients) to compare results over 12 weeks. Ideal candidates for this trial have psoriatic arthritis with chronic back pain and have tried at least two different non-steroidal anti-inflammatory drugs (NSAIDs) without success. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

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 is the safety track record for Upadacitinib?

Research shows that upadacitinib is consistently safe. Studies have found no new safety issues, even with long-term use. Patients have used upadacitinib for several years without any new risks appearing, indicating that the treatment is generally well-tolerated. Overall, evidence suggests that upadacitinib is safe for treating conditions like psoriatic arthritis. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Upadacitinib is unique because it targets the Janus kinase (JAK) pathway, which plays a crucial role in the inflammatory processes of psoriatic arthritis. Unlike standard treatments like methotrexate or TNF inhibitors that broadly suppress the immune system, upadacitinib specifically inhibits JAK enzymes, potentially offering more precise control of inflammation with fewer side effects. Researchers are excited about upadacitinib because it offers a different mechanism of action, which could benefit patients who haven't responded well to other treatments or who experience significant side effects.

What is the effectiveness track record for Upadacitinib in treating psoriatic arthritis?

Research has shown that upadacitinib, which participants in this trial may receive, effectively treats psoriatic arthritis. One study found that 66% of patients with this condition experienced significant improvements with upadacitinib. Another study confirmed its effectiveness over 24 weeks, demonstrating its efficacy and safety in everyday use. Upadacitinib has also provided lasting benefits for up to 12 months, with many patients continuing its use. Thorough studies have revealed no new safety issues, making it a promising choice for people with psoriatic arthritis. ^{2 6 7 8 9}

Who Is on the Research Team?

Walter Maksymowych, Dr.

Principal Investigator

CARE ARTHRITIS LTD.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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 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 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, 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]

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 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]

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]

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]

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, 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9569172/

2-Year Results from the Phase 3 SELECT-PsA 1 Study Similar efficacy, including improvements in peripheral arthritis, was observed with upadacitinib 15 mg and 30 mg. Furthermore, no new safety risks were ...

2. arthritis-research.biomedcentral.com arthritis-research.biomedcentral.com/articles/10.1186/s13075-023-03182-9

Upadacitinib effectiveness and factors associated with ... The 24-week results from the UPREAL-PsA study confirm the remarkable efficacy and good safety profile of upadacitinib therapy in real-life PsA, ...

3. rheumatologyadvisor.com rheumatologyadvisor.com/news/upa-shows-sustained-efficacy-in-axial-and-peripheral-psa/

UPA Shows Sustained 12 Month Efficacy and Safety in PsA Upadacitinib persistence at 12 months was 75.1%, with higher rates found among patients with peripheral-only vs mixed PsA (P =.039) and lower ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0003496725022435

5-YEAR RESULTS FROM THE PHASE 3 SELECT-PsA 1 ... In total, 1704 patients received ≥ 1 dose of study drug and 983 (57.7%) patients completed 260 weeks of treatment. Across all patients, the most common primary ...

5. rinvoqhcp.com rinvoqhcp.com/psoriatic-arthritis/efficacy

RINVOQ® (upadacitinib) Efficacy for Psoriatic Arthritis SELECT-PsA 2 Biologic DMARD-IR Patient data: 66% of patients achieved. *PASI assessed in patients with psoriatic skin involvement of ≥3% BSA at baseline.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11111431/

Safety Profile of Upadacitinib up to 5 Years in Psoriatic ... Upadacitinib 15 mg demonstrated a generally consistent safety profile across disease states with no new safety signals identified.

7. arthritis-research.biomedcentral.com arthritis-research.biomedcentral.com/articles/10.1186/s13075-023-03027-5

Efficacy and safety of upadacitinib in patients with active ... Overall BASDAI score improvements were greater with upadacitinib 15 mg versus placebo at weeks 12 and 24 in both studies and according to both ...

8. rmdopen.bmj.com rmdopen.bmj.com/content/9/1/e002735

Safety profile of upadacitinib over 15 000 patient-years ... A definitive safety outcomes study like ORAL Surveillance has not been conducted with upadacitinib and whether the potential increased risk of ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03104374

NCT03104374 | A Study Comparing Upadacitinib (ABT- ... This is a Phase 3 multicenter study that included two periods. Period 1 was designed to compare the safety, tolerability, and efficacy of upadacitinib 15 mg ...