Guselkumab improves diverse psoriatic arthritis manifestations through 1 year
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Guselkumab demonstrates sustained benefits for multiple, diverse manifestations of psoriatic arthritis through 1 year, according to data published in Rheumatology.
“The study is obviously a further look at the trial data with guselkumab in PsA,” Laura Coates, MBChB, MRCP, PhD, of the University of Oxford, and the lead author of the study, told Healio. “Whilst the studies usually focus on single domain outcomes as primary outcome (eg, ACR20) for regulatory reasons, we are increasingly interested in the response using composite measures. These help us to understand response in PsA overall, taking into account multiple domains like arthritis, enthesitis and skin disease.”
To further investigate the safety and efficacy of guselkumab (Tremfya, Janssen) in patients with PsA, Coates and colleagues analyzed data from the DISCOVER-1 and DISCOVER-2 trials. In DISCOVER-1, the classification criteria for PsA were three or more each of tender and swollen joints and a serum C-reactive protein level of 0.3 mg per dL or greater. In DISCOVER-2, the criteria were stricter, with a minimum swollen and tender joint count of five each, and a CRP of 0.6 mg per dL or greater. Additionally, all patients in DISCOVER-2 were biologic-naïve.
Patients in both studies were randomized 1:1:1 to receive either subcutaneous guselkumab 100 mg every 4 weeks; guselkumab 100 mg at weeks 0 and 4, then every 8 weeks; or placebo every 4 weeks until week 24, when they switched to guselkumab 100 mg every 4 weeks.
Prespecified endpoints for both studies included the proportion of patients who achieved Disease Activity Index for Psoriatic Arthritis (DAPSA) low disease activity, remission, and Psoriatic Arthritis Disease Activity Score (PASDAS) low disease activity and remission. The authors pooled data from both trials for the current study.
DAPSA was calculated as the sum of tender joint count, swollen joint count, patient pain assessment, patient global and assessment of arthritis activity. DAPSA low disease activity was defined as a score of 13 or less, while remission was defined as four or less. Patients achieved PASDAS LDA if they had a score of 3.2 or lower, and achieved a very LDA score if they reached 1.9 or less.
A total of 1,120 patients were included in the current analysis. According to the researchers, there were greater proportions of patients receiving guselkumab than those receiving placebo who reached DAPSA low disease activity or remission, PASDAS low disease activity or very low disease activity at week 24 (P < .05).
At week 52, DAPSA low disease activity rates were 54.2% and 52.5% among patients receiving once-every-4-week doses (Q4W) and once-every-8-week (Q8W) doses, respectively. Additional response rates among the Q4W and Q8W guselkumab groups were 18.2% and 17.6% for DAPSA remission, 45.3% and 41.9% for PASDAS LDA, 16.9% and 19.5% for PASDAS very low disease activity, 35.9% and 30.7% for minimum disease activity, and 13.1% and 14.4% for very low disease activity, respectively. In the placebo group, patients saw an increased response rate after switching to guselkumab at week 24.
“The study showed that patients treated with guselkumab had a higher chance of achieving all of the composite and remission/low disease activity outcomes compared to placebo,” Coates said. “This was true for measures of arthritis remission like DAPSA remission but also for multiple domain outcomes like minimum disease activity and PASDAS, showing that a good level of disease control can be reached across multiple domains.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Play Ball! Scoring in rheumatology has progressed from the days when Ted Pincus would lecture us to “Measure something!” to seeing the extent of scoring that was referenced in this post-hoc analysis of the DISCOVER-1 and DISCOVER-2 studies. The authors analyzed four composite indices: Disease Activity Index for Psoriatic Arthritis (DAPSA), Psoriatic Arthritis Disease Activity Score (PASDAS), minimal disease activity (MDA) and very low disease activity (VLDA). DAPSA was further subdivided into DAPSA and DAPSA that excluded CRP (cDAPSA).
Over 52 weeks, multiple visits had the calculation to determine scores for DAPSA LDA, DAPSA remission, PASDAS LDA, PASDAS VLDA, MDA, and VLDA. They also analyzed the PsA-modified van der Heijde-Sharp scores from DISCOVER-2. The DAPSA scores were calculated as the sum of Tender Joint Count (range of 0 to 68), Swollen Joint Count (range of 0 to 66), patient pain assessment (0 cm to 10 cm visual analogue scale [VAS]), patient global assessment (GA) of arthritis activity (0 cm to 10 cm VAS), and CRP (mg/dL). The higher the score the more severe the disease with ≤14 defined as LDA and ≤4 as remission.
PASDAS scores were calculated based on a formula that included physician global assessment of skin and joints (0 mm to 100 mm VAS), patient global opinion of skin and joints (0 mm to 100 mm VAS), 36-item Short Form Health Survey physical component summary score (range of 0 to 100), SJC (0 to 66), TJC (0 to 68), Leeds Enthesitis Index (LEI) score (range of 0 to 6), tender dactylitis count (range of 0 to 20), and CRP (mg/L). As you can see, lots of measurements looking at all facets of psoriasis and psoriatic arthritis.
PASDAS LDA was defined as ≤3.2 and PASDA VLDA ≤1.9. MDA and VLDA criteria included the scoring of 7 outcomes: TJC ≤1, SJC ≤1, LEI ≤1, Psoriasis Area and Severity Index (PASI) score ≤1, patient pain VAS ≤15 mm (range of 0 to 100), Patient GA of the maximum component of either psoriasis activity or PsA activity VAS ≤20 mm (range of 0 to 100), and a Health Assessment Questionnaire-Disability Index (HAQ-DI) score of ≤0.5 (range of 0 to 3). Meanwhile, MDA was defined as <5 and VLDA <7.
PsA-modified van der Heijde-Sharp scores were compared to those achieving and not achieving PASDAS LDA, DAPSA LDA and MDA responses at week 24. Patient reported outcomes were included in all scores except for radiology, as the FDA has been requesting. This certainly was a comprehensive analysis of the psoriasis patient with arthritis, dactylitis, and enthesitis.
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