Comparison of remission and low disease activity states with DAPSA, MDA and VLDA in a clinical trial setting in psoriatic arthritis patients: 2-year results from the FUTURE 2 study.

Remission (REM) or low disease activity (LDA) states were compared in a clinical trial setting of the FUTURE 2 study (NCT01752634) using Disease Activity Index for Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) composite indices in secukinumab treated PsA patients. The proportion of patients reaching DAPSA-REM (cut-off ≤4) or REM+LDA (≤14), and very low disease activity (VLDA; achieving 7/7 criteria) or MDA (≥5/7), were compared in the overall population, by prior use of anti-TNF therapy, and by time since diagnosis using as observed data. The proportion of patients who met individual core component and other variables of interest were also computed to assess residual disease activity in DAPSA-REM/REM+LDA states and VLDA/MDA responses. The relationship between DAPSA/MDA and patient reported outcomes (PROs), including health-related quality of life, physical function, and fatigue were assessed using mixed model for repeated measures. More patients could achieve DAPSA-REM or DAPSA-REM+LDA status than VLDA or MDA responses, respectively, at all the time points in the overall population, irrespective of anti‒TNF status and time since diagnosis. Higher proportion of patients reaching DAPSA-REM or VLDA achieved more thresholds of core components (joints, pain, patient and physician global assessments, and function) than DAPSA-REM+LDA or MDA over Week 104. There were differences with numerically higher proportion of patients achieving patient global assessment ≤10 mm and ≤20 mm, and physician global assessment ≤10 mm with MDA than with DAPSA-REM+LDA, and patient pain VAS ≤15 mm, PASI ≤1, HAQ ≤0.5 with VLDA or MDA than with DAPSA-REM or DAPSA-REM+LDA, respectively, through 104 weeks. Improvements in PROs were significantly better for patients in DAPSA-REM+LDA versus DAPSA-moderate+high disease activity status, and for MDA responders versus non-responders. These analysis add to the evidence that both DAPSA and MDA composite index measures can be used for evaluation of the status and treatment response utilizing a treat to target approach in PsA patients in a clinical trial setting and improve patient health related outcomes. The study and analysis was funded by Novartis Pharma AG, Basel, Switzerland.

Coates LC ，Nash P ，Kvien TK ，Gossec L ，Mease PJ ，Rasouliyan L ，Pricop L ，Jugl SM ，Gandhi KK ，Gaillez C ，Smolen JS ... -  《-》

Comparison of disease activity index for psoriatic arthritis (DAPSA) and minimal disease activity (MDA) targets for patients with psoriatic arthritis: A post hoc analysis of data from phase 3 tofacitinib studies.

To compare achievement of Disease Activity Index in Psoriatic Arthritis (DAPSA) remission (REM)/low disease activity (LDA) with very low disease activity (VLDA)/minimal disease activity (MDA) targets in tofacitinib-treated patients with psoriatic arthritis (PsA). In this post hoc analysis, data were pooled from two phase 3 studies (6 months' [NCT01882439] and 12 months' [NCT01877668] duration) of patients with PsA receiving tofacitinib 5 or 10 mg twice daily. Cut-offs for DAPSA targets: ≤4 for clinical REM and >4-≤14 for LDA. VLDA and MDA were defined as meeting 7 or ≥5, respectively, of 7 criteria. An ordered logistic regression model was performed to evaluate associations between baseline characteristics and achievement of DAPSA targets as well as VLDA/MDA at month 3. Agreement between achieving DAPSA and VLDA/MDA targets at months 1-6 was assessed via kappa tests. Change from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) scores (month 6), modified Total Sharp Score (mTSS) and proportion of radiographic non-progressors (mTSS ≤0.5) at month 12 (NCT01877668 only) were compared across DAPSA and VLDA/MDA targets. Increased disease activity at baseline was associated with reduced likelihood of achieving DAPSA-REM/DAPSA-LDA or VLDA/MDA at month 3. There was moderate agreement (kappa values 0.41-0.60) between DAPSA-REM and VLDA, and DAPSA-LDA and MDA, from months 1 to 6, although over half of patients achieving DAPSA-REM and over two thirds of patients achieving DAPSA-LDA, respectively, were not captured by VLDA and MDA. Achieving DAPSA-REM/DAPSA-LDA or VLDA/MDA was associated with improved HAQ-DI and SF-36 PCS scores at month 6, and slightly reduced radiographic progression at month 12. This analysis of data from tofacitinib-treated patients with PsA demonstrated moderate agreement between the DAPSA and VLDA/MDA composite instruments. In agreement with previous studies, VLDA and MDA may be more difficult to achieve than DAPSA-REM and DAPSA-LDA, respectively. However, the clinical and prognostic relevance of this finding should be determined. These data support DAPSA and VLDA/MDA as useful tools for evaluating disease activity and treatment response in PsA. GOV: NCT01882439; NCT01877668.

Schneeberger EE ，Citera G ，Nash P ，Smolen JS ，Mease PJ ，Soriano ER ，Helling C ，Szumski AE ，Mundayat R ，de León DP ... -  《-》

Remission and low disease activity in psoriatic arthritis publications: a systematic literature review with meta-analysis.

Remission (REM) or low disease activity (LDA) is the treatment target in psoriatic arthritis (PsA). The objective of this study was to assess the reporting and prevalence of REM/LDA in published studies of PsA. This was a systematic literature review of all clinical papers published in PubMed, EMBASE or Cochrane database in English between 2012 and 2019 in the field of PsA. Data were collected regarding reporting of REM/LDA by very low disease activity/minimal disease activity (VLDA/MDA), Disease Activity index for Psoriatic Arthritis (DAPSA), or Disease Activity Score 28 joints (DAS28). The pooled rates of REM and LDA by each definition were calculated by random effect meta-analysis. In all, 258 publications (corresponding to 114 651 patients), of which 81 (31%) were randomized controlled trials, were analysed: patients' mean age was 49.4 ( 4.4) years; with a mean disease duration of 8.5 ( 3.8) years. REM/LDA was reported in 91/258 (35.3%) publications. VLDA/MDA was used in 61/91 (67.0%) studies, DAPSA in 27/91 (29.6%) and DAS28 in 28/91 (30.7%), with 40/91 (43.9%) papers reporting several of these definitions. The pooled prevalence (lower-upper limits) of REM was 13.1% (10.9-15.4), 23.1% (16.8-30.1) and 42.1% (33.9-50.4) using VLDA, DAPSA-REM and DAS28, respectively. For LDA the pooled prevalence was 36.3% (32.3-40.5), 52.8% (41.8-63.6) and 60.4% (52.5-68.0) using MDA, DAPSA-LDA and DAS28, respectively. REM/LDA status was reported in only1/3 of recent studies on PsA, with important variations in the frequency of these outcomes according to the definition used: 13.1-42.1% for REM, and 36.3-60.4% for LDA. This highlights the need for consensus.

Hagège B ，Tan E ，Gayraud M ，Fautrel B ，Gossec L ，Mitrovic S ... -  《-》

Secukinumab improves physical function and quality of life and inhibits structural damage in patients with PsA with sustained remission or low disease activity: results from the 2-year phase 3 FUTURE 5 study.

To investigate the impact of sustained low disease activity (LDA)/remission (REM) on physical function, quality of life (QoL) and structural outcomes in secukinumab-treated psoriatic arthritis (PsA) patients from the FUTURE 5 study. FUTURE 5 was a randomised, double-blind, placebo-controlled, parallel-group, phase 3 study in patients with active PsA. Patients were categorised according to LDA (Minimal Disease Activity, MDA/Disease Activity index for Psoriatic Arthritis, DAPSA LDA+REM) or REM (very LDA/DAPSA REM): not achieving LDA/REM, achieving it once or sustained LDA/REM ≥3 times up to week 104. Key outcomes were improvements in Health Assessment Questionnaire Disability Index and Short Form-36 Physical Component Summary Score, proportion of non-radiographic progressors and predictors of sustained LDA response. Patients were randomised (N=996) into the following treatment groups: secukinumab 300 mg (N=222), secukinumab 150 mg loading (N=220)/non-loading (N=222) and placebo (N=332). Baseline characteristics were comparable between patients with sustained DAPSA and MDA responses. By week 104, 48%-81% and 19%-36% of the secukinumab-treated patients achieved sustained LDA and REM, respectively. Numerically greater improvements in physical function and QoL were observed with sustained LDA/REM versus LDA/REM achieved once or not at all, although patients reached the established minimal clinically important difference for all composite indices. A high proportion of secukinumab-treated patients were non-structural progressors at 2 years irrespective of achieving sustained LDA/REM. Younger age, lower body mass index at baseline, reduced tender joint count and PsA pain at week 16 were key predictors of sustained LDA in secukinumab-treated patients. Sustained LDA/REM was associated with improvements in physical function, QoL and inhibition of structural damage progression.

Coates LC ，Mease PJ ，Gladman DD ，Navarra S ，Bao W ，Gaillez C ... -  《-》

Comparing patient-perceived and physician-perceived remission and low disease activity in psoriatic arthritis: an analysis of 410 patients from 14 countries.

The objective was to compare different definitions of remission and low disease activity (LDA) in patients with psoriatic arthritis (PsA), based on both patients' and physicians' perspectives. In ReFlap (Remission/Flare in PsA; NCT03119805), adults with physician-confirmed PsA and >2 years of disease duration in 14 countries were included. Remission was defined as very low disease activity (VLDA), Disease Activity index for PSoriatic Arthritis (DAPSA) ≤4, and physician-perceived and patient-perceived remission (specific question yes/no), and LDA as minimal disease activity (MDA), DAPSA <14, and physician-perceived and patient-perceived LDA. Frequencies of these definitions, their agreement (prevalence-adjusted kappa), and sensitivity and specificity versus patient-defined status were assessed cross-sectionally. Of 410 patients, the mean age (SD) was 53.9 (12.5) years, 50.7% were male, disease duration was 11.2 (8.2) years, 56.8% were on biologics, and remission/LDA was frequently attained: respectively, for remission from 12.4% (VLDA) to 36.1% (physician-perceived remission), and for LDA from 25.4% (MDA) to 43.9% (patient-perceived LDA). Thus, patient-perceived remission/LDA was frequent (65.4%). Agreement between patient-perceived remission/LDA and composite scores was moderate to good (kappa range, 0.12-0.65). When patient-perceived remission or LDA status is used as reference, DAPSA-defined remission/LDA and VLDA/MDA had a sensitivity of 73.1% and 51.5%, respectively, and a specificity of 76.8% and 88.0%, respectively. Physician-perceived remission/LDA using a single question was frequent (67.6%) but performed poorly against other definitions. In this unselected population, remission/LDA was frequently attained. VLDA/MDA was a more stringent definition than DAPSA-based remission/LDA. DAPSA-based remission/LDA performed better than VLDA/MDA to detect patient-defined remission or remission/LDA. Further studies of long-term outcomes are needed.

Gorlier C ，Orbai AM ，Puyraimond-Zemmour D ，Coates LC ，Kiltz U ，Leung YY ，Palominos P ，Cañete JD ，Scrivo R ，Balanescu A ，Dernis E ，Tälli S ，Ruyssen-Witrand A ，Soubrier M ，Aydin SZ ，Eder L ，Gaydukova I ，Lubrano E ，Kalyoncu U ，Richette P ，Husni ME ，de Wit M ，Smolen JS ，Gossec L ... -  《-》