Efficacy of Secukinumab Compared to Ustekinumab in Adults With Active Psoriatic Arthritis and Failure of TNFα-Inhibitor Treatment

Novartis Pharmaceuticals119 enrolled

Overview

The purpose of this study is to compare the safety and efficacy of secukinumab and ustekinumab in patients with active psoriatic arthritis who showed failure to previous TNFα-inhibitor treatment

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

119

Conditions

Psoriatic Arthritis

Interventions

SecukinumabBIOLOGICAL

Eligible subjects are randomized to one of two treatment arms in a 1:1 ratio

UstekinumabBIOLOGICAL

Eligible subjects are randomized to one of two treatment arms in a 1:1 ratio

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Diagnosis of PsA as classified by CASPAR criteria for at least 6 months before randomization. * Active PsA at baseline defined as ≥ 3 tender joints out of 68 and ≥ 3 swollen joints out of 66 (dactylitis of a digit counts as one joint each). * Inadequate response or intolerance to previous or current treatment with at least one TNFα inhibitor * Inadequate response or intolerance to conventional disease modifying anti-rheumatic drugs (cDMARDs) * Diagnosis of active plaque psoriasis, with at least one psoriatic plaque of ≥ 2 cm diameter and/or nail changes consistent with psoriasis and/or documented history of plaque psoriasis. * Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies negative at screening. Key Exclusion Criteria: * Pregnant or nursing women, * Previous exposure to secukinumab, ustekinumab or any other biologic drug directly targeting IL-17, IL-17 receptor, IL-12 or IL-23. * Patients for whom the use of secukinumab or ustekinumab is contraindicated. * Use of any other investigational drug. Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 or investigational agents * Evidence of ongoing infectious or malignant process * Subjects receiving high potency opioid analgesics * Ongoing use of prohibited psoriasis treatments/medications Other protocol-defined inclusion/exclusion criteria may apply

Locations (28)

Novartis Investigative Site

Rendsburg, Schleswig-Holstein, Germany

Outcomes

Primary Outcomes

Proportion of Patients With Health Assessment Questionnaire - Disability Index (HAQ-DI) Response at Week 28

The disability assessment component of the HAQ evaluated a subject's level of functional ability through 20 questions grouped into 8 categories: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item began with the prompt "Over the past week, are you able to…" and is scored on a 4-point scale: 0 (no difficulty), 1 (some difficulty), 2 (much difficulty), and 3 (unable to do). The overall score was calculated by averaging the scores across all answered domains, resulting in a total score ranging from 0 (no disability) to 3 (severe disability). A HAQ-DI response was defined as an improvement of ≥0.35 points from baseline at Week 28. Missing values were imputed as non-responders

Time frame: Baseline, Week 28

Secondary Outcomes

Number of Participants Achieving Psoriasis Area and Severity Index (PASI) 90 Response at Week 28

The Psoriasis Area and Severity Index (PASI) was a composite measure that evaluates the average severity of erythema, induration, and desquamation of psoriatic lesions-each graded on a scale from 0 (none) to 4 (severe)-across four body regions: head, upper limbs, trunk (including groin), and lower limbs (to the top of the buttocks). These scores were weighted by the area of skin involvement in each region to generate a total PASI score ranging from 0 to 72, with higher scores indicating more severe disease activity. The number of participants who achieved at least a 90% reduction in PASI score from baseline at Week 28 was assessed. Missing values were imputed as non-responders.

Time frame: Baseline, Week 28

Change From Baseline in Patient's Assessment of Pain on VAS at Week 28

The patient's level of pain was evaluated using a horizontal Visual Analogue Scale (VAS), on which individuals marked their pain intensity with a vertical tick. The scale ranged from 0 mm (indicating "no pain") to 100 mm (indicating "unbearable pain"). The change in the patient's pain assessment on the VAS from baseline to Week 28 was analyzed. A negative change from baseline indicated improvement.

Data from ClinicalTrials.gov

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Novartis Investigative Site

Aachen, Germany

Novartis Investigative Site

Bad Bentheim, Germany

Novartis Investigative Site

Bad Doberan, Germany

Novartis Investigative Site

Berlin, Germany

Novartis Investigative Site

Berlin, Germany

Novartis Investigative Site

Berlin, Germany

Novartis Investigative Site

Bochum, Germany

Novartis Investigative Site

Cologne, Germany

Novartis Investigative Site

Cologne, Germany

...and 18 more locations

Time frame: Baseline, Week 28

Change From Baseline in Tender Joint Count (TJC) 68 at Week 28

Tender joint count (TJC) 68 was a method of assessing joint inflammation. Number of tender joints was determined by examining 68 joints and identifying the joints that were painful under pressure or to passive motion. The 68 joints assessed for tenderness included the 2 temporomandibular, 2 sternoclavicular, 2 acromioclavicular joints, 2 shoulders, 2 elbows, 2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal, 8 distal interphalangeal joints of the hands, 2 hips, 2 knees, 2 talo¬tibial, 2 mid-tarsal, 10 metatarsophalangeal, and 10 proximal interphalangeal joints of the feet. The change from baseline in TJC68 at Week 28 was assessed. A negative change from baseline indicated improvement.

Time frame: Baseline, Week 28

Change From Baseline in Swollen Joint Count (SJC) 66 at Week 28

Swollen Joint Count (SJC) 66 was a method of assessing joint inflammation. The number of swollen joints was determined by examining 66 joints and identifying those with visible or palpable swelling suggestive of synovitis. The 66 joints assessed for swelling included the 2 sternoclavicular, 2 acromioclavicular joints, 2 shoulders, 2 elbows, 2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal, 8 distal interphalangeal joints of the hands, 2 knees, 2 talotibial, 2 mid-tarsal, 10 metatarsophalangeal, and 10 proximal interphalangeal joints of the feet. The change from baseline in SJC66 at Week 28 was assessed. A negative change from baseline indicated improvement.

Time frame: Baseline, Week 28

Number of Patients Achieving PASI 100 at Week 28

The PASI was a composite measure that evaluates the average severity of erythema, induration, and desquamation of psoriatic lesions-each graded on a scale from 0 (none) to 4 (severe)-across four body regions: head, upper limbs, trunk (including groin), and lower limbs (to the top of the buttocks). These scores were weighted by the area of skin involvement in each region to generate a total PASI score ranging from 0 to 72, with higher scores indicating more severe disease activity. The number of participants who achieved 100% reduction in PASI score from baseline at Week 28 was assessed. Missing values were imputed as non-responders.

Time frame: Bseline, Week 28

Number of Patients Achieving PASI 75 at Week 28

The Psoriasis Area and Severity Index (PASI) was a composite measure that evaluates the average severity of erythema, induration, and desquamation of psoriatic lesions-each graded on a scale from 0 (none) to 4 (severe)-across four body regions: head, upper limbs, trunk (including groin), and lower limbs (to the top of the buttocks). These scores were weighted by the area of skin involvement in each region to generate a total PASI score ranging from 0 to 72, with higher scores indicating more severe disease activity. The number of participants who achieved at least a 75% reduction in PASI score from baseline at Week 28 was assessed. Missing values were imputed as non-responders.

Time frame: Baseline, Week 28

Change From Baseline in Patient's Global Assessment of Disease Activity on VAS

The patient's global assessment of disease activity was performed using a 100 mm (VAS) ranging from 0 (='very good') to 100 (='very poor') after the question 'Considering all the ways Psoriatic Arthritis affects you, please indicate with a vertical mark through the horizontal line how well you are today'. The change in the patient's global assessment on the VAS from baseline to Week 28 was analyzed. A negative change from baseline indicated improvement.

Time frame: Baseline, Week 28

Change From Baseline in Patient's Global Assessment of Psoriasis and Arthritis Disease Activity on VAS

The patient's assessment of psoriasis and arthritis was performed using a 100 mm VAS ranging from 0 (='Excellent') to 100 (='Poor') after the question 'Considering all the ways PSORIASIS and ARTHRITIS affects you, please indicate with a vertical mark through the horizontal line how well you are doing over the past week' The change in the patient's global assessment of psoriasis and arthritis disease activity on the VAS from baseline to Week 28 was analyzed. A negative change from baseline indicated improvement.

Time frame: Baseline, Week 28

Number of Patients Achieving Minimal Disease Activity (MDA) at Week 28

MDA was a composite endpoint used to assess low disease activity in patients with psoriatic arthritis and psoriasis. A patient was considered to have achieved MDA if they met at least 5 of the following 7 criteria: * TJC (0-68)≤1 * SJC (0-66 joints)≤1 * PASI ≤1 \[the total score ranged from 0 (no disease) to 72 (maximal disease)\] or body surface area≤3% * Patient's pain VAS ≤ 15 mm on a 100 mm scale, where 0 ="no pain" and 100= "pain as severe as can be imagined" * Patient's global assessment of disease activity (PtGA) ≤ 20 mm on a 100 mm scale, where 0 represented the lowest level of disease activity and 100 the highest * HAQ-DI ≤ 0.5, where 0 represented no difficulty and 3 represented inability to perform activities * Enthesitis count ≤ 1, based on the Leeds Enthesitis Index, where 0 indicated no tenderness and 6 indicated tenderness at all assessed tendon insertions The number of participants achieving MDA at Week 28 was assessed. Missing values were imputed as non-responders.

Time frame: Week 28

Change From Baseline in the Leeds Enthesitis Index (LEI)

The LEI was a validated enthesitis index that used six sites to evaluate enthesitis: the left and right lateral epicondyles of the humerus, the left and right proximal Achilles tendon insertions, and the left and right medial femoral condyles.Each site was scored as 0 (non-tender) or 1 (tender), resulting in a total score ranging from 0 to 6. A higher score reflected a greater burden of enthesitis. The change in the LEI score from baseline to Week 28 was analyzed. A negative change from baseline indicated an improvement in enthesitis severity

Time frame: Baseline, Week 28

Change From Baseline in the Leeds Dactylitis Index (LDI)

The LDI was used to quantitatively assess dactylitis by measuring the circumference of affected digits and their corresponding control digits, along with the tenderness of each affected digit. Digits were classified as dactylitic if there was a ≥10% difference in circumference compared to the contralateral digit. When both digits were affected or a contralateral control was unavailable, a standardized reference range was applied. For each dactylitic digit, the ratio of the affected to control circumference was multiplied by a binary tenderness score (1 = tender, 0 = non-tender). The resulting values were summed across all affected digits to calculate the total LDI score. Scores ranged from 0 to 20, with higher scores indicating more severe or widespread dactylitis. The change in the LDI score from baseline to Week 28 was analyzed. A negative change from baseline indicated an improvement in dactylitis severity.

Time frame: Baseline, Week 28

Change From Baseline in Psoriatic Arthritis Quality of Life (PsAQoL)

The PsAQoL questionnaire was used to assess the impact of psoriatic arthritis on patients' quality of life. The PsAQoL is a validated, disease-specific, self-administered instrument consisting of 20 items with binary response options ("true" or "not true"). Items covered physical, emotional, and social domains, including fatigue, independence, and interpersonal relationships. The total score ranged from 0 to 20, with higher scores indicating greater impairment in quality of life. The change in the PsAQoL score from baseline to Week 28 was analyzed. A negative change from baseline indicated an improvement in health-related quality of life.

Time frame: Baseline, Week 28

Percentage of Participants Achieving a Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Response at Week 28

The FACIT-Fatigue Scale was used to assess fatigue and its impact on daily functioning over the previous 7 days. The instrument consisted of 13 self-administered items, each scored on a 5-point Likert scale ranging from 0 ("Not at all") to 4 ("Very much"). The total score ranged from 0 to 52, with higher scores indicating less fatigue and better functioning. Response was achieved if the score had improved by at least 4 points from baseline. Missing values were imputed as non-responders

Time frame: Baseline, Week 28

Percentage of Participants Achieving a Dermatology Life Quality Index (DLQI) Response at Week 28

The DLQI was used to evaluate the impact of dermatological conditions on patients' quality of life over the previous 7 days. It consisted of 10 self-administered items covering symptoms, daily activities, leisure, work/school, personal relationships, and treatment burden. Each item was scored from 0 ("Not at all") to 3 ("Very much"), with a total score ranging from 0 to 30. Higher scores indicated greater impairment. Response was achieved if the absolute score was either 0 or 1. Missing values were imputed as non-responders.

Time frame: Week 28