Achievement Of Minimal Disease Activity Research Articles

Early Oligoarticular Psoriatic Arthritis Responds to Treatment With Apremilast: Week 16 Results From FOREMOST - a Phase 4 Randomized Controlled Trial

Early Oligoarticular Psoriatic Arthritis Responds to Treatment With Apremilast: Week 16 Results From FOREMOST – a Phase 4 Randomized Controlled Trial
 Laure Gossec1, Dafna Gladman2, Laura C. Coates3, Jacob Aelion4, Jitendra Vasandani5, Jyotsna Reddy6, Rebecca Wang6, Michele Brunori6, Stephen Colgan6, Philip Mease7
 1Sorbonne Université and Pitié Salpêtrière Hospital, Paris, France; 2Toronto Western Hospital, Toronto, ON, Canada; 3University of Oxford, Oxford, UK; 4West Tennessee Research Institute, Jackson, TN, USA; 5West Texas Clinical Research, Lubbock, TX, USA; 6Amgen Inc., Thousand Oaks, CA, USA; 7Swedish Medical Center/Providence St. Joseph Health and University of Washington School of Medicine, Seattle, WA, USA
 Introduction & Objectives:
 Psoriatic arthritis (PsA) is underdiagnosed in dermatology practice, typically presenting 10 years after skin symptoms. Dermatologists may encounter early PsA since up to 30% of patients with psoriasis have PsA. Oligoarticular PsA affects ≤4 joints, is very common, and is underrepresented in clinical trials as most pivotal studies exclude patients with <3 swollen and tender joints. Here, we report the efficacy and safety of apremilast vs. placebo for the treatment of early oligoarticular PsA.
 Materials & Methods:
 FOREMOST (NCT03747939) is a phase 4, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Patients with PsA,based on CAPSAR criteria, duration ≤5 years, swollen joint count (SJC) >1 but ≤4, and tender joint count (TJC) >1 but ≤4 were randomized 2:1 to apremilast 30 mg BID (APR) or placebo for 24 weeks. The primary endpoint was the achievement of minimal disease activity (MDA)-Joints1 (mandating SJC ≤1 and TJC ≤1, and 3/5 alternate items) at week 16.
 Results:
 Of 308 patients randomized (APR: n=203; placebo: n=105), mean PsA duration was 9.9 months, mean age was 50.9 years, and 39.9% of patients were using csDMARD. MDA-Joints response was achieved in 33.9% vs. 16.0% for patients treated with APR vs. placebo (primary endpoint, P=0.0008). At week 16, a significantly greater proportion, 70.2%, of patients treated with APR achieved cDAPSA REM/LDA vs. 51.8% with placebo (P=0.0017). A greater proportion of patients achieved a good/moderate response in PASDAS score with APR (59.9%) vs. placebo (42.7%). Greater improvements from baseline in PsA Impact of Disease (PsAID)-12 score (LS mean change, −1.5 vs. −0.4; nominal P<0.0001) and nail psoriasis score (visual analog scale [VAS]; LS mean change, −13.9 vs. −6.8; nominal P=0.0094) were observed with APR vs. placebo at week 16. Patients treated with APR also achieved greater improvement in quality of life measures (Patient Pain [VAS ≤15: 59.6 vs. 13.8; nominal P=0.0022], Patient Global Assessment [PtGA; VAS ≤20: 61.7 vs. 20.1; nominal P=0.0286]) when compared to placebo at week 16. No new safety signals were identified.
 Conclusion:
 FOREMOST is the first global randomized controlled trial exclusively studying early oligoarticular PsA. We report the first results of FOREMOST, the primary outcome, and show better disease control is achievable with APR, with twice the MDA-Joint response compared with placebo at 16 weeks. These findings show APR treatment of early oligoarticular PsA improves clinical and quality of life outcomes and may inform optimal management of these patients.
 Reference: 1. Coates LC, et al. J Rheumatol. 2016;43:371–5.

Continuous improvement through differential trajectories of individual minimal disease activity criteria with guselkumab in active psoriatic arthritis: post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled study

BackgroundTo explore the trajectory of, and factors contributing to, achievement of individual criteria of minimal disease activity (MDA) in patients with active psoriatic arthritis (PsA) treated with guselkumab.MethodsThe Phase 3, randomized, placebo-controlled DISCOVER-2 study enrolled adults (N = 739) with active PsA despite standard therapies who were biologic/Janus kinase inhibitor-naive. Patients were randomized 1:1:1 to guselkumab 100 mg every 4 weeks; guselkumab 100 mg at week 0, week 4, then every 8 weeks; or placebo. In this post hoc analysis, patients randomized to guselkumab were included and pooled (N = 493). Longitudinal trajectories of achieving each MDA criterion through week 100 were derived using non-responder imputation. Time to achieve each criterion was estimated with Kaplan-Meier analysis. Multivariate regression for time to achieve each criterion (Cox regression) and achievement at week 100 (logistic regression) was used to identify contributing factors.ResultsContinuous improvement across all MDA domains was shown over time. ~70% of patients achieved near remission in swollen joint count (SJC), Psoriasis Area and Severity Index (PASI), and enthesitis through week 100. Median times to achieve individual criteria differed significantly (p < 0.0001), with SJC ≤ 1 (20 weeks), PASI ≤ 1 (16 weeks), and ≤ 1 tender entheses (16 weeks) being faster than patient-reported criteria (pain ≤ 15 mm, patient global assessment of arthritis and psoriasis ≤ 20 mm, Health Assessment Questionnaire-Disability Index ≤ 0.5) and tender joint count ≤ 1. Higher baseline domain scores, older age, worse fatigue, and increased body mass index were significant predictors of longer time to achieve minimal levels of disease activity assessed via patient-reported criteria.ConclusionsSubstantial proportions of guselkumab-treated patients achieved individual MDA criteria, each showing continuous improvement through week 100, although with distinct trajectories. Median times to achieve physician-assessed MDA criteria were significantly faster compared with patient-driven criteria. Identification of modifiable factors affecting the time to achieve patient-reported criteria has the potential to optimize the achievement and sustainability of MDA in the clinic via a multidisciplinary approach to managing PsA, involving both medical and lifestyle interventions.Trial registration numberNCT03158285.Trial registration dateMay 16, 2017.

Search for predictors of achieving minimal disease activity during tofacitinib therapy in patients with psoriatic arthritis

Objective: to search predictors of achieving minimal disease activity (MDA) during therapy in patients with psoriatic arthritis (PsA).Materials and methods. The study included 41 patients, predominantly men (58.9 %), with a confirmed PsA diagnosis and a disease duration of at least 6 months. In all cases, the diagnosis fulfilled the CASPAR criteria. The mean age of the patients at the time of enrolment in the study was 43.0±10.1 years, the duration of PsA was 7.7±7.1 years, the duration of psoriasis was 18.6±10.4 years, and the DAPSA index was 44.2±17.1. All patients were prescribed tofacitinib at a dose of 5 mg twice daily, followed by a possible dose increase to 10 mg twice daily. In addition to a general clinical examination and a standard rheumatological examination, the level of secreted DKK-1 protein and health-related quality of life (HRQoL, using a special PsAID-12 questionnaire) were determined. Multivariate stepwise discriminant analysis was used to search for predictors for the achievement of MDA in patients with PsA and to calculate the coefficients.Results and discussion. Based on the results obtained, a predictor for the achievement of MDA (PMDA) was developed: PMDA=-1.165 × number of inflamed entheses + DKK-1 level (pmol/l) + 3.086 × PsAID-12 “Skin lesions” scale value (if this indicator was ≤3 points, it was assigned a value of 1, if it was &gt;3 points – 0) + 2.568 × PsAID-12 “Pain” scale (if this indicator was ≤6 points, it was assigned a value of 1, if it was &gt;6 points – 0).The ROC analysis, which reflects the prognostic significance of this index, showed AUC (area under the curve) of 0.803 (95% confidence interval 0.739–0.867; p=0.02). PMDA=3.89 was chosen as the cut-off value; the sensitivity of this indicator was 91 %, the specificity – 79 %. Therefore with a PMDA ≥3.89, the probability of the patient achieving a MDA after 3 months is high; with a PMDA ˂ 3.89, it is low.Conclusion. We identified factors influencing the achievement of MDA in patients with PsA and developed a mathematical model. It allows timely assessment of the quality of treatment and its correction if necessary, thereby slowing disease progression.

Factors associated with achieving an acceptable health-related quality of life in the treatment of patients with psoriatic arthritis

Objective: to analyze factors associated with the achievement of acceptable health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA) 7 years after the start of observation.Material and methods. The study included 53 patients (28 women, 25 men) with PsA who met the 2006 CASPAR criteria. The mean age of patients was 45.7±12.0 years, the median duration of PsA was 90 [72; 99] months, and the observation period was 81 [61; 91] months. The study included patients in early stage of PsA (duration up to 2 years), who were treated according to the “treat-to-target” strategy (T2T) for 24 months. Subsequently, all patients continued therapy according to the standards of medical care under the supervision of the treating physician. Over time, a standard rheumatological examination was performed. Activity of PsA was assessed by DAPSA, psoriasis by BSA, HRQoL by Psoriatic Arthritis Impact of Disease (PsAID-12); body mass index (BMI, kg/m2 ) and functional status by HAQ were also assessed. PsAID-12 ≤4 corresponded to achieving a Patient Acceptable State Status (PASS). The results were analyzed in two groups of patients: PsAID-12 ≤4 and PsAID-12 &gt;4. The number of patients (%) who achieved minimal disease activity (MDA) after 1–2 years of active treatment and after 7 years was assessed. X-rays of the hands and feet (n=42) were performed using standard methods, changes were assessed using the Sharp/van der Heijde method modified for PsA (m-Sharp/van der Heijde).Results and discussion. After 7 years, 38 (71.7%) of 53 patients were found to have PASS. Patients who achieved PASS had significantly lower PsA and psoriasis activity, lower CRP levels, lower m-Sharp/van der Heijde scores, better functional status and HRQoL, and lower BMI at baseline. Factors associated with achieving PASS were identified: absence of nail psoriasis, BSA ≤3%, CRP ≤5 mg/l, number of swollen joints ≤3, number of painful joints ≤5, HAQ ≤0.5 at baseline and after 24 months, and achievement of MDA during the first 12 months of treatment.Conclusion. The majority of PsA patients treated at an early stage according to T2T principles had PASS, which is associated with low disease activity, fewer joint erosions, better functional status and achievement of MDA during the first 12 months of therapy. These factors should be considered when predicting disease progression.

Maintenance of Response to Risankizumab in Patients With Psoriatic Arthritis: A 3-year Analysis of the KEEPsAKE 1 and 2 Trials

Introduction: Risankizumab, a humanized immunoglobulin G1 monoclonal antibody, specifically inhibits the p19 subunit of human interleukin 23 and is approved for treatment of active psoriatic arthritis (PsA) in adults. This post hoc analysis evaluated the long-term maintenance of clinical response through ~3 years of risankizumab treatment using data from 2 ongoing phase 3 trials, KEEPsAKE 1 and KEEPsAKE 2.&#x0D; Methods: Eligible patients had active PsA with inadequate response or intolerance to ≥1 conventional synthetic disease modifying antirheumatic drugs (KEEPsAKE 1 [NCT03675308]; KEEPsAKE 2 [NCT03671148]) and/or inadequate response or intolerance to 1–2 biologic therapies (KEEPsAKE 2 only). Patients received double-blinded risankizumab 150 mg or placebo at weeks 0, 4, and 16 and open-label risankizumab 150 mg every 12 weeks thereafter. This analysis includes patients who received continuous risankizumab through both treatment periods. Assessments included improvement of ≥20%/50%/70% in PsA symptoms using American College of Rheumatology criteria (ACR20/50/70), achievement of minimal disease activity (MDA), reduction of ≥90% in Psoriasis Area and Severity Index (PASI 90; in patients with ≥3% body surface area affected by psoriasis at baseline), and clinically meaningful reduction in pain (≥10 mm on a visual analog scale [VAS]). Maintenance of response analyses were based on patients who were responders at weeks 24 or 52 for each endpoint. Nonresponder imputation incorporating multiple imputation (NRI-MI) for missing data due to COVID-19 or geopolitical conflict was used. As-observed data were also reported.&#x0D; Results: Among patients receiving continuous risankizumab, ACR20 was achieved at week 24 in 267/454 (KEEPsAKE 1, 58.8%) and 111/208 (KEEPsAKE 2, 53.4%) patients (as observed). Maintenance of response in week 24 ACR20 responders (NRI-MI) was achieved for ACR20 by most patients at week 52 (KEEPsAKE 1, 89.1%; KEEPsAKE 2, 77.0 %) and week 148 (KEEPsAKE 1, 74.7%; KEEPsAKE 2; 68.5%). Similar patterns of maintenance of response were observed for ACR50 and ACR70. Week 24 responders also maintained MDA at weeks 52 (KEEPsAKE 1, 82.2%; KEEPsAKE 2, 66.7%) and 148 (KEEPsAKE 1, 77.1%; KEEPsAKE 2, 71.9%). The PASI 90 response was maintained at weeks 52 (KEEPsAKE 1, 86.6%; KEEPsAKE 2, 88.4%) and 148 (KEEPsAKE 1, 76.3%; KEEPsAKE 2, 81.2%). Week 24 responders maintained clinically meaningful reductions in pain VAS at weeks 52 (KEEPsAKE 1, 83.9%; KEEPsAKE 2, 74.4%) and 148 (KEEPsAKE 1, 75.0%; KEEPsAKE 2, 72.0%). Comparable maintenance of response was recorded at week 148 for each endpoint among week 52 responders (NRI-MI).&#x0D; Conclusion: Risankizumab demonstrated durable long-term efficacy in patients with active PsA. A high proportion of patients receiving continuous risankizumab treatment in KEEPsAKE 1 and KEEPsAKE 2 achieved responses in ACR20/50/70, MDA, PASI 90, or pain VAS at weeks 24 or 52 and maintained responses through week 148.

Upadacitinib effectiveness and factors associated with minimal disease activity achievement in patients with psoriatic arthritis: preliminary data of a real-life multicenter study

BackgroundUpadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA.MethodsOne hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis.ResultsAt baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs. At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 ± 13.5 (p < 0.001) for DAPSA and 1.21 ± 0.97 (p < 0.001) for ASDAS-CRP. Thirteen patients (10%) discontinued UPA due to a lack of efficacy or non-serious adverse events. No serious adverse events were observed. Male gender (OR 2.54, 95% CI 1.03–6.25 p = 0.043), being naïve to biological DMARDs (OR 4.13, 95% CI 1.34–12.71, p = 0.013) and elevated baseline CRP (OR 2.49, 95% CI 1.02–6.12, p = 0.046) were associated with MDA response at week 24.ConclusionsThis is one of the first real-life studies supporting the effectiveness of UPA and its safety profile in PsA patients. Furthermore, the study identifies predictors of MDA response to UPA treatment at 6 months.

Identification of the Minimal Disease Activity Domains Achieved Based on Different Treatments in Psoriatic Arthritis.

The aim of this work is to characterize which Minimal Disease Activity (MDA) domains are mainly achieved, based on different treatments, in psoriatic arthritis (PsA) patients. Moreover, the association between MDA achievement and thedifferent treatment groups was assessed. We conducted a cross-sectional analysis of two longitudinal PsA groups. Inclusion criteria were: age ≥ 18years, PsA diagnosis, stable treatment for at least 6months. Patients were grouped depending on the therapy: group 1: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)/cyclooxygenase 2 inhibitors (COX2i)/steroids, group 2: conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs), group 3: Tumor Necrosis Factorα inhibitors (TNFi), group 4: interleukininhibitors (IL)12-23i or IL-23i, group 5: IL-17i, group 6: phosphodiesterase 4inhibitors (PD4i). For each group, the achieved domains based on therapy were assessed. Multivariate logistic regression analysis was performed to assess the association between the treatment groups and the MDA achievement. A total of 220 patients were enrolled, and MDA was achieved in 45.8% of them. In all treatment groups, the first MDA domains achieved were: body surface area ≤ 3, swollen joint count ≤ 1 and Leeds Enthesitis Index ≤ 1, while MDA domains less frequently achieved were Patient Global Assessment (PtgA) ≤ 2cm and pain on visual analogue scale ≤ 1.5cm. The logistic regression analysis showed higher odds ratios for the achievement of the MDA in those patients in groups 3 and 4. In each treatment group, MDA domains less frequently achieved were PtGA and pain, suggesting that "patient-driven domains" are still an unmet need. Due to the study design and the low number of patients in some groups, it is not possible to clearly define which MDA domain was achieved or not based on treatment; however, it seems that some differences could be present. If larger and prospective studies confirm our preliminary results, we could move toward a personalized/domain treatment approach in PsA.

403 Achievement of minimal disease activity is associated with improvements in symptoms, quality of life and treatment satisfaction in patients with atopic dermatitis

Abstract There is a need for clear criteria to guide treatment decisions and disease management in patients with atopic dermatitis (AD). The recently developed minimal disease activity (MDA) concept aims to optimize AD management through shared decision-making between patients and clinicians in a treat-to-target approach, and is based on consensus recommendations from 87 physicians and insights from 88 patients globally.This study aims to evaluate how achieving MDA affects outcomes in patients with AD. Observed-case data from three phase 3 clinical trials involving adolescents and adults with moderate-to-severe AD were integrated and analysed (NCT03568318, NCT03569293 and NCT03607422). The MDA criteria were applied to clinician-reported measures [Eczema Area and Severity Index (EASI), SCORing of Atopic Dermatitis, validated Investigator Global Assessment, and body surface area] and patient-reported measures [Worst Pruritus Numerical Rating Scale (WP-NRS), Patient-Oriented Eczema Measure, Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain score, Atopic Dermatitis Impact Scale (ADerm-IS) Sleep disturbance score, Hospital Anxiety and Depression Scale and Dermatology Life Quality Index]. Patients were stratified into three mutually exclusive groups by achievement of treatment targets per measurement at week 16: (i) achieving the optimal target (i.e. MDA) criteria [e.g. EASI improvement ≥90% (EASI 90); WP-NRS ≤1], (ii) achieving the moderate but not optimal target criteria [e.g. EASI improvement ≥75% and &amp;lt;90%; WP-NRS improvement (reduction) ≥4 and WP-NRS &amp;gt;1] and (iii) not achieving either target criteria. Among the stratified target groups (optimal, moderate and neither), patients’ symptoms, quality of life, work productivity and treatment satisfaction were assessed based on achieving meaningful clinically important differences in ADerm-SS 7-item total symptom score (ADerm-SS TSS-7; improvement ≥28), ADerm-IS Daily Activities score (improvement ≥14), ADerm-IS Emotional State score (improvement ≥11), percentage-point improvement in Work Productivity and Activity Impairment (WPAI) Overall Work Productivity score and proportion reporting Patient Global Impressions of Treatment of ‘Extremely/Very Satisfied’. Stratified target groups were compared with a chi-squared or t-test for categorical or continuous variables, respectively, based on observed data. This analysis included 2392 patients. Patients in the optimal target (MDA) group based on EASI (EASI 90) vs. those in the moderate or neither target group had a higher proportion reporting meaningful improvements in ADerm-SS TSS-7 (optimal = 82.6% vs. moderate = 56.8% or neither = 27.4%; P &amp;lt; 0.001 for both comparisons), ADerm-IS Daily Activities (87.2% vs. 66.2% or 39.9%; both P &amp;lt; 0.001) and ADerm-IS Emotional State (86.1% vs. 67.1% or 36.8%; both P &amp;lt; 0.001); a greater percentage-point improvement in WPAI Overall Work Productivity (36.8% vs. 29.2% or 16.6%; both P &amp;lt; 0.01); and a higher proportion reporting being very/extremely satisfied with treatment (73.5% vs. 54.0% or 23.5%; both P &amp;lt; 0.001). Patients in the optimal target (MDA) group based on itch (WP-NRS ≤1) vs. those in the moderate or neither target group had a higher proportion reporting meaningful improvements in ADerm-SS TSS-7 (94.3% vs. 79.7% or 19.1%; both P &amp;lt; 0.001), ADerm-IS Daily Activities (97.3% vs. 84.7% or 33.6%; both P &amp;lt; 0.001) and ADerm-IS Emotional State (94.5% vs. 84.5% or 31.7%; both P &amp;lt; 0.001); a greater percentage-point improvement in WPAI Overall Work Productivity [39.7% vs. 35.2% (not significant) or 14.6% (P &amp;lt; 0.001)]; and a higher proportion reporting being very/extremely satisfied with treatment (79.7% vs. 60.5% or 26.8%; both P &amp;lt; 0.001). Trends were similar in other clinician- and patient-reported measures, with patients who achieved MDA generally reporting better outcomes. Achieving MDA from both a clinician and patient perspective was generally associated with greater improvements in AD symptoms, daily activities, emotional state, work productivity and higher satisfaction. These results demonstrate the value of achieving MDA and support implementing MDA in clinical practice to help improve the current standard of AD care.

Prognostic factors associated with achieving minimal disease activity in early psoriatic arthritis patients treated according to “treat-to-target” st rategy within 12 months

Background. The goal of “treat-to-target” strategy (T2T) in psoriatic arthritis (PsA) is attaining remission or minimal disease activity (MDA). The benefits of T2T are shown recently in the study TICOPA and REMARCA. But prognostic factors for achievement MDA in PsA patients (pts) at the early-stage hasn’t been studied yet.Objective – to determine the prognostic factors associated with achievement of minimal disease activity within 12 months (mo) of treatment according to T2T strategy in early psoriatic arthritis patients.Methods. 77 pts (M/F=36/41) with early PsA fulfilling the CASPAR criteria were included. Mean age 36.9±10.45 years, PsA duration 11.1±10.0 mo, psoriasis duration 82.8±92.1 mo. At baseline (BL) and at 12 mo of therapy PsA activity by tender joins count (TJC) out of 68; swelling joints count (SJC) out of 66; pain; patient global assessment disease activity (PGA) using visual analogue scale; CRP; dactylitis, enthesitis by LEI and plantar fascia; BSA; HAQ and fatigue by FACIT 4 scale were evaluated. A score FACIT &lt;30 indicates severe fatigue, the higher the score – the better the quality of life. All pts were given therapy with Methotrexate (MTX) s/c, 29 pts with ineffectiveness of MTX after 3–9 mo of treatment were added biologic DMARDs. The one-factor model of logistic regression was used to identify a group of features that are associated with achievement MDA.Results. By 12 mo of therapy, the proportion of pts who have reached MDA (5/7) were calculated. Pts were split into 2 groups: MDA+ (n=45) and MDA– (n=32).Comparative analysis of BL features in both groups and one-factor model of logistic regression showed the following features were associated with achievement MDA: TJC and SJC&lt;3 (p&lt;0.001); PGA≤20 mm (p&lt;0.001); pain≤15 mm (p&lt;0.001); CRP≤5 mg/l (p&lt;0.03); HAQ≤0.5 (p&lt;0.001); FACIT&gt;30 points (p&lt;0.021); absent of entesitis (p&lt;0.003), dactylitis (p&lt;0.029) and nail damage (p&lt;0.012). Early PsA pts with combination of these features on first visit have more chance to achieve MDA in comparison to PsA pts without them (OR=9.684 [95% CI: 4.6–20.4]).Conclusion. It is a combination of features on first visit – oligoarthritis, moderate activity, absent of entesitis, dactylitis, nail psoriasis, significant impact on function and fatigue – that constitutes a clinical prognostic factors for achievement MDA after 12 mo of treatment in pts with early PsA according T2T.

Minimal disease activity and remission in patients with psoriatic arthritis with elevated body mass index: an observational cohort study in the Swiss Clinical Quality Management cohort

ObjectiveTo assess the impact of elevated body mass index (BMI) in the achievement of minimal disease activity (MDA) and several definitions of remission in patients with psoriatic arthritis (PsA) in...

POS1029 EFFECTS OF TREATMENT WITH RISANKIZUMAB ON MINIMAL DISEASE ACTIVITY (MDA) AND DISEASE ACTIVITY IN PSORIATIC ARTHRITIS (DAPSA): AN ANALYSIS OF THE KEEPsAKE-1 AND -2 TRIALS

BackgroundRisankizumab (RZB) is a monoclonal antibody that specifically inhibits interleukin 23.ObjectivesTo evaluate the achievement of Minimal Disease Activity (MDA), its components, and achievement of Disease Activity in PsA Low Disease Activity and Remission (DAPSA LDA+REM, [DAPSA score ≤14]) in patients receiving RZB or placebo (PBO) in the KEEPsAKE 1 and 2 clinical trials.MethodsKEEPsAKE-1 and -2, double-blind, phase 3 trials, evaluated the efficacy of RZB versus PBO for the treatment of adult patients with active psoriatic arthritis (PsA). Patients were randomized (1:1) to receive subcutaneous RZB 150 mg or PBO at weeks 0, 4, and 16. The open label extension began at Week 24 with all patients receiving RZB 150 mg every 12 weeks thereafter. Achievement of MDA, its components, and achievement of DAPSA LDA+REM are reported using non-responder imputation.ResultsMDA achievement at Week 52 in KEEPsAKE-1 was 37.9% for patients originally randomized to RZB and 27.4% for patients originally randomized to PBO. In KEEPsAKE-2, MDA achievement was 27.2% and 33.8% for patients originally randomized to RZB and PBO, respectively. Achievement of MDA and its components are presented in Figure 1. In KEEPsAKE-1, at Week 52 59.2% of patients originally randomized to RZB and 51.4% of patients originally randomized to PBO achieved DAPSA LDA+REM. At Week 52 in KEEPsAKE-2, DAPSA LDA+REM was achieved by 44.6% of patients originally randomized to RZB and 46.6% of patients originally randomized to PBO (Figure 1).ConclusionPatients treated with RZB demonstrate achievement of MDA, its components, and DAPSA LDA+REM at Weeks 24 and 52.AcknowledgementsAbbVie Inc, participated in the study design; study research; collection, analysis and interpretation of data; and writing, reviewing, and approving of this abstract for submission. AbbVie funded the research for this study and provided writing support for this abstract. Medical writing assistance was provided by Trisha Rettig, Ph.D. of AbbVieDisclosure of InterestsJoseph F. Merola Consultant of: Amgen, Bristol-Myers Squibb, Abbvie, Dermavant, Eli Lilly, Novartis, Janssen, UCB, Sanofi, Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma, Iain McInnes Consultant of: AbbVie, Amgen, Astra Zeneca, Compugen, Cabaletta, Evelo, Janssen, Lilly, Novartis, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Amgen, Astra Zeneca, Janssen, Lilly, Novartis, Pfizer, UCB, Arthur Kavanaugh Consultant of: AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, Grant/research support from: AbbVie Inc., Amgen, Astra-Zeneca, BMS, Celgene, Centocor-Janssen, Pfizer, Roche, and UCB, Peter Nash Speakers bureau: Abbvie, Amgen, Janssen, Lilly, Novartis, Pfizer, UCB, BMS, Rocje, Sanofi, Gilead/Galapagos, MSD, Samsung, Celgene, Amgen, Boehringer, Consultant of: Abbvie, Amgen, Janssen, Lilly, Novartis, Pfizer, UCB, BMS, Rocje, Sanofi, Gilead/Galapagos, MSD, Samsung, Celgene, Amgen, Boehringer, Grant/research support from: Abbvie, Amgen, Janssen, Lilly, Novartis, Pfizer, UCB, BMS, Rocje, Sanofi, Gilead/Galapagos, MSD, Samsung, Celgene, Amgen, Boehringer, Zhenyi Xue Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Vassilis Stakias Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Ann Eldred Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Sandra Ciecinski Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Kevin Douglas Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Laura Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis and Pfizer

P271 To what extent are baseline characteristics in biologic-experienced patients with psoriatic arthritis associated with achievement of minimal disease activity at week 24 of guselkumab treatment: a post hoc analysis of the phase IIIb COSMOS clinical trial

Abstract Background/Aims Guselkumab (GUS), a human monoclonal antibody targeting the interleukin-23p19-subunit, has demonstrated efficacy at Week 24 (W24) in the Phase IIIb COSMOS clinical trial of patients with active psoriatic arthritis (PsA) and inadequate response or intolerance to one or two tumour necrosis factor inhibitors (TNFis). This post hoc analysis aimed to identify predictors of minimal disease activity (MDA) with GUS at W24 in this population. Methods Multiple logistic regression analysis was performed to identify potential predictors of MDA with GUS at W24 in TNFi-refractory patients with PsA; odds ratios, 95% confidence intervals and p-values were calculated. Baseline characteristics assessed as predictors included sex, body mass index (BMI), C-reactive protein (CRP), other medication use and disease duration; clinical features included tender and swollen joint counts (TJC/SJC), affected joint location, dactylitis, enthesitis, spondylitis, Psoriasis Area Severity Index (PASI) score and psoriasis (PsO) localisation (Table). Missing data for MDA at W24 were imputed as non-response; missing baseline values were imputed for two patients. Results Patients (n = 187; female, 54.6%; mean disease duration, 8.3 years) had mean TJC 0-68 and SJC 0-66 of 21.0 and 10.3, respectively, mean PASI score of 11.6, and mean BMI of 28.9; 67.9% had enthesitis and 35.8% had dactylitis at baseline. One prior TNFi had been received by 88.2% of patients, with two received by 11.8%. At W24, 17.1% (32/187) of patients achieved MDA. Wrist involvement (p = 0.031) and scalp PsO (p = 0.049) were positive predictors of MDA. Women were significantly less likely to achieve MDA vs. men; other negative predictors included hand small joints or shoulder involvement and hand/foot PsO (all p &amp;lt; 0.05). Age, BMI, CRP, TJC/SJC, HAQ-DI, PASI, spondylitis, enthesitis, dactylitis, other medication and number of prior TNFis were not predictive of MDA (Table). Conclusion Baseline characteristics and clinical features may be positively (wrist involvement, scalp PsO) or negatively (female sex, hand small joints or shoulder involvement, hand/foot PsO) associated with achieving MDA with GUS at W24 in a TNFi-refractory population. Though the low patient number limits the generalisability of this analysis, assessment of Week 48 data may further elucidate potential predictors of MDA after longer-term treatment. Disclosure W. Tillett: Other; William Tillett has received research grants and consulting or speaker fees from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer and UCB. S. Ohrndorf: Other; Sarah Ohrndorf has received fees from AbbVie, BMS, Janssen, Novartis and Pfizer. J. Ramírez: Other; Julio Ramírez has received consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis and UCB. M. Neuhold: Other; Marlies Neuhold is an employee of Janssen and owns stocks in Johnson &amp; Johnson. R. Wapenaar: Other; Robert Wapenaar is an employee of Janssen and owns stocks in Johnson &amp; Johnson. E. Theander: Other; Elke Theander is an employee of Janssen and owns stocks in Johnson &amp; Johnson. C. Contre: Other; Christine Contre is an employee of Janssen and owns stocks in Johnson &amp; Johnson. M. Sharaf: Other; Mohamed Sharaf is an employee of Janssen and owns stocks in Johnson &amp; Johnson. M. Shawi: Other; May Shawi is an employee of Janssen and owns stocks in Johnson &amp; Johnson. M. Vis: Other; Marijn Vis has received research grants and consulting or speaker fees from AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB and the Dutch Arthritis Foundation.

Effectiveness of 6-month Use of Secukinumab in Patients With Psoriatic Arthritis in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

To evaluate clinical and patient-reported outcomes (PROs) at 6 months after secukinumab initiation in US patients with psoriatic arthritis (PsA). Patients with PsA in the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry who initiated secukinumab between April 1, 2017, and December 2, 2019, and maintained secukinumab at their 6-month follow-up visit were included. Achievement of minimal disease activity (MDA) among patients not in MDA at initiation; resolution (ie, no evidence) of tender and swollen joint counts, enthesitis, and dactylitis among patients with ≥ 1 of these at initiation; and change in disease activity and PROs were evaluated at 6 months in all patients and in patients who received secukinumab as a first-line biologic. Of the 100 eligible patients included, most (83.0%) were biologic experienced and 17.0% initiated secukinumab as a first-line biologic. At initiation, 75/90 patients (83.3%) with available data were not in MDA; 26/71 (36.6%) with follow-up data achieved MDA at 6 months. Further, 28/68 patients (41.2%) with ≥ 1 tender joint, 24/54 (44.4%) with ≥ 1 swollen joint, 17/28 (60.7%) with enthesitis, and 9/12 (75.0%) with dactylitis at initiation achieved resolution at 6 months. Improvements in clinical manifestations, PRO measures, and work productivity and activity were observed after 6 months among patients with PsA who initiated and maintained secukinumab. In this real-world population, patients with PsA who received and maintained secukinumab for 6 months achieved MDA in proportions consistent with clinical trials and demonstrated improvements in clinical manifestations and PROs.

P172 Quality of life improvements in patients with PsA who achieve remission or low disease activity targets: results from two clinical trials of ixekizumab at three years of treatment

P172 Quality of life improvements in patients with PsA who achieve remission or low disease activity targets: results from two clinical trials of ixekizumab at three years of treatment

Achievement of minimal disease activity in psoriatic arthritis according to the time of administration of synthetic disease-modifying antirheumatic drugs, a comparative analysis of the efficacy of oral and subcutaneous methotrexate. Data from the All-Russian Psoriatic Arthritis Registry

The goal of psoriatic arthritis (PsA) therapy is to achieve remission or minimal disease activity (MDA). According to the EULAR guidelines, synthetic disease-modifying antirheumatic drugs (sDMARDs), methotrexate (MTX) in particular, are first-line therapy for PsA.Objective: to study the rate of MDA achievement after initiation of sDMARD therapy in patients with early- and late-stage PsA and the efficacy of oral and parenteral MTX.Patients and methods. The investigation enrolled 253 patients (93 men and 160 women) diagnosed with PsA who met the appropriate 2006 CASPAR (ClASsification criteria for Psoriatic ARthritis) criteria and were recorded in the All-Russian PsA Registry. The median (Me) age was 47 (Min 20 – Max 82) years. All the patients took sDMARDs: MTX (n=211) that was received orally (as tablets) (n=102) and parenterally (n=109); leflunomide (n=7); sulfasalazine (n=24); apremilast (n=10); and tofacitinib (n=1). According to the disease duration at sDMARD treatment initiation, the patients were divided into two groups. Group 1 included 165 patients with an early PsA duration of less than 2 years and Group 2 consisted of 88 patients with a disease duration of &gt;2 years. The efficiency of oral and parenteral MTX was evaluated in 182 patients (68 men and 114 women). Every 6 months, the patients underwent a standard rheumatology examination that included PsA activity assessment. The efficiency of MTX therapy was evaluated from MDA achievement (5 out of the 7 criteria) in the patients.Results and discussion. After sDMARD prescription, MDA was achieved in 39 (24%) of the 165 patients with early PsA and in 4 (5%) of the 88 long-term patients. The patients who started sDMARD at an early stage of the disease were significantly more likely to achieve MDA than those with late-stage PsA (odds ratio (OR) 6.5; 95% confidence interval (CI) 2.2–18.9). At 11 years after sDMARD therapy initiation, the cumulative MDA achievement rate in the patients with late-stage disease was 5% (p&lt;0.05). MDA was achieved by 16.5% of the 182 patients receiving oral or subcutaneous MTX. MDA was observed in 25 (31%) patients who received parenteral MTX and in only 5 (5%) patients who took oral MTX. The patients who received parenteral MTX were significantly more likely to achieve MDA than those who took oral MTX as tablets (OR 8.8; 95% CI 3.2–24.3). Following 27-month parenteral MTX therapy, the cumulative rate of MDA achievement was 48%, whereas after oral MTX treatment, that was 7% (p&lt;0.05). In the patients who achieved MDA, the mean dose of parenteral MTX was 17 mg/week, and in those who failed, that was 15 mg/week. The mean dose of oral MTX was 15 mg/week, regardless of MDA achievement.Conclusion. The administration of sDMARD at an early stage of PsA lasting less than 2 years allows MDA to be achieved significantly more often and faster than at later stages of the disease. Among sDMARDs, preference is mostly given to the use of MTX in real clinical practice; the treatment with the latter enables 16.5% of patients to achieve MDA. Parenteral MTX significantly enhances the efficiency of therapy and can achieve MDA in almost one third (31%) of patients.

Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2

BackgroundUpadacitinib is a Janus kinase inhibitor under evaluation for the treatment of psoriatic arthritis (PsA). We evaluated upadacitinib in patients with PsA and prior inadequate response or intolerance to at...

SAT0429 SECUKINUMAB IMPROVES CLINICAL AND PATIENT-REPORTED OUTCOMES AT 6 MONTHS AMONG PATIENTS WITH PSORIATIC ARTHRITIS IN THE US-BASED CORRONA PSORIATIC ARTHRITIS/SPONDYLOARTHRITIS (PsA/SpA) REGISTRY

Background:Secukinumab, an interleukin-17 antagonist approved for the treatment of PsA, improves all PsA manifestations in the GRAPPA-OMERACT core domain set.1Few US-based studies have evaluated the real-world effectiveness of secukinumab in patients with PsA.Objectives:To examine clinical and patient-reported outcomes (PROs) in patients with PsA enrolled in the Corrona PsA/SpA registry initiating secukinumab with ≥ 1 follow-up visit.Methods:Included were adult patients with PsA in the Corrona registry who initiated secukinumab after April 1, 2017 and remained on secukinumab at their 6-month (window, 5-8 months) follow-up visit. The primary outcome was achievement of minimal disease activity (MDA) at 6 months among patients not in MDA at secukinumab initiation. MDA was defined as meeting 5 of the 7 following criteria: tender joint count (TJC) ≤ 1, swollen joint count (SJC) ≤ 1, psoriasis affected body surface area (BSA) &lt; 3%, patient assessment of pain on visual analog scale (VAS) ≤ 15, patient global assessment VAS ≤ 20, HAQ-DI ≤ 0.5, and tender entheseal points ≤ 1 using the Leeds Enthesitis Index (LEI). Secondary outcomes included the proportion of patients who achieved resolution (0 sites) of TJC, SJC, enthesitis (using the LEI), and dactylitis among those with ≥ 1 site at initiation and improvement from baseline in clinical outcomes (BSA, nail psoriasis, physician global assessment, TJC, SJC, and DAPSA) and PROs (patient-reported pain, patient global assessment, HAQ-DI, and Work Productivity and Activity Impairment questionnaire) at 6 months. Outcomes were evaluated in the overall population and in potentially recalcitrant patients with failure of or intolerance to ≥ 3 previous biologics to examine if the later line biologic could be adequately effective.Results:A total of 100 patients with PsA who initiated and maintained secukinumab after 6 months were included. The mean (SD) age was 51.6 (11.6) years, 54.3% were male, and 96.8% were white. The mean (SD) symptom and disease duration were 10.8 (9.7) and 7.0 (7.0) years, respectively. Thirty patients (30.0%) initiated secukinumab 150 mg and 70 (70.0%) initiated secukinumab 300 mg. Most (83.0%) were biologic experienced; 17 patients initiated secukinumab as a 1st biologic, 34 as 2nd, 26 as 3rd, and 23 as ≥ 4th. At initiation, 75/90 patients (83.3%) were not in MDA; 26/71 (36.6%) of those with follow-up data available achieved MDA at 6 months (Figure 1). In the overall population, 28 patients (41.2%) with TJC ≥ 1, 24 (44.4%) with SJC ≥ 1, 17 (60.7%) with enthesitis, and 9 (75.0%) with dactylitis at initiation achieved resolution at 6 months (Table 1). Improvement was observed at 6 months in clinical outcomes and PROs in the overall population (Figures 1 and 2) and in patients who initiated secukinumab as a ≥ 4th-line biologic.Table 1.Resolution of Peripheral Arthritis, Enthesitis, and Dactylitis at 6 Months Among Patients With ≥ 1 Site at InitiationSecondary OutcomesInitiation,Mean (SD) [n]6-Month Follow-Up,Resolution (Count = 0), n (%)TJC (1-68)9.0 (9.7) [68]28 (41.2)SJC (1-66)4.7 (4.2) [54]24 (44.4)Enthesitis (1-6)1.9 (1.1) [28]17 (60.7)Dactylitis (1-20)2.1 (1.3) [12]9 (75.0)Conclusion:In the Corrona registry, most secukinumab initiators with PsA were biologic experienced and were not in MDA at time of initiation. Consistent with clinical trials, real-world patients treated with secukinumab achieved MDA as well as improvement in clinical manifestations, PROs, and work productivity.

OP0050 ADALIMUMAB INTRODUCTION VERSUS METHOTREXATE DOSE ESCALATION IN PATIENTS WITH INADEQUATELY CONTROLLED PSORIATIC ARTHRITIS: RESULTS FROM RANDOMIZED PHASE 4 CONTROL STUDY

Background:Methotrexate (MTX) is often used as first-line therapy for patients (pts) with psoriatic arthritis (PsA) despite limited efficacy and data on appropriate dosage. Minimal Disease Activity (MDA) is suggested as an optimal treat-to-target outcome. Biologic disease-modifying antirheumatic drugs (bDMARDs) have demonstrated improved outcomes (including MDA rates) over MTX. However, more data are needed to define the optimal timing of bDMARD initiation and characterize efficacy of MTX dose escalation, to achieve optimal outcomes.Objectives:To compare achievement of MDA between adding adalimumab (ADA) vs escalating MTX dose in PsA pts with inadequate disease control after initial MTX therapy.Methods:The open-label, 2-part CONTROL study enrolled bDMARD-naive adult pts with active PsA (not in MDA at screening and ≥3 tender and ≥3 swollen joints) despite MTX 15 mg every wk (ew) for ≥4 wks. Pts were randomized to ADA 40 mg every other wk + MTX 15 mg (ADA+MTX) or escalated MTX to 20–25 mg ew or highest tolerable dose during 16-wk part 1 (Fig 1). The primary endpoint was achievement of MDA, defined as fulfilling ≥5 of the 7 criteria: tender joint count 68 (TJC68) ≤1, swollen joint count 66 (SJC66) ≤1, Psoriasis Area Severity Index (PASI) ≤1 or body surface area (BSA) ≤3%, pt’s pain (visual analogue scale [VAS] 0–100) ≤15, Pt’s Global Assessment of disease activity (PtGA) VAS ≤20, Health Assessment Questionnaire Disability Index (HAQ-DI) ≤0.5 and tender entheseal points (0–8) ≤1. Key secondary efficacy endpoints were achievement of ACR20 and PASI75 and change from baseline in HAQ-DI and Leeds Enthesitis Index (LEI) at wk 16.Results:Overall, 246 pts were randomized; 245 received treatment (ADA+MTX, n=123; escalated MTX, n=122); 117 (95%) pts and 110 (90%) pts, respectively, completed part 1. Baseline characteristics were similar between groups (Table). During part 1, the average dose of MTX was 21.8 mg/wk (55% on oral MTX) in the escalated MTX group. Significantly higher proportion of pts in ADA+MTX (42%) vs escalated MTX (13%) group achieved MDA at wk 16 (non-responder imputation [NRI]; difference [95% CI] 28% [18%–39%];P&lt;0.001;Fig 2). Observed case analysis confirmed the NRI analysis. Lower MDA rates at wk 16 were observed in the escalated MTX arm regardless of prior MTX duration (Fig 2). Significant improvements in key secondary endpoints were also observed with ADA+MTX vs escalated MTX (allP&lt;0.05;Fig 2). In part 1, the proportion of patients with adverse events was similar between groups (ADA+MTX, 62% vs escalated MTX, 57%); no opportunistic infections, tuberculosis, malignancies, or deaths were reported during part 1.Conclusion:A significantly higher proportion of pts achieved MDA at wk 16 after introducing ADA compared with escalating MTX dose; higher rates were observed regardless of prior MTX duration. Significantly higher responses in musculoskeletal, skin, and quality of life measures were observed with ADA+MTX vs escalated MTX. No new safety signals with ADA were identified in this pt population.Table 1.Baseline DemographicsCharacteristics, mean (SD)ADA+MTXn=123Escalated MTXn=122Female, n (%)64 (52.0)59 (48.4)Age, y51.4 (12.2)48.8 (12.7)BSA &gt;3%, n (%)74 (60.2)78 (63.9)Pt pain63.7 (19.5)62.3 (20.9)PtGA65.0 (19.9)62.9 (20.9)HAQ-DI1.2 (0.6)1.2 (0.7)LEI + plantar count3.5 (2.1)3.5 (2.1)Disclosure of Interests:Laura C Coates: None declared, William Tillett Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc, UCB, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Frank Behrens Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Lilly and Roche, Consultant of: Pfizer, AbbVie, Sanofi, Lilly, Novartis, Genzyme, Boehringer, Janssen, MSD, Celgene, Roche and Chugai, Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Erin McDearmon-Blondell Shareholder of: AbbVie, Employee of: AbbVie, Xianwei Bu Shareholder of: AbbVie, Employee of: AbbVie, Liang Chen Shareholder of: AbbVie, Employee of: AbbVie, Mudra Kapoor Shareholder of: AbbVie, Employee of: AbbVie, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Exploration of the Product of the 5-Point Investigator’s Global Assessment and Body Surface Area (IGA × BSA) as a Practical Minimal Disease Activity Goal in Patients with Moderate-to-Severe Psoriasis

Background/Aims: In the treat-to-target era, psoriasis disease activity measures that can be easily performed in routine clinical practice are needed. This retrospective pooled analysis explored cutoff values of the product of the 5-point Investigator’s Global Assessment and percentage of affected body surface area (IGA × BSA) correlating with achievement of minimal disease activity (MDA). Methods: Post hoc analysis of the phase 3 clinical trials ERASURE, FIXTURE, FEATURE, and JUNCTURE was conducted to determine associations between IGA × BSA and 2 MDA definitions (Psoriasis Area and Severity Index [PASI] 90 and Dermatology Life Quality Index [DLQI] 0/1, or PASI score ≤1 or BSA <3%) in patients with moderate-to-severe psoriasis receiving secukinumab 300 mg. For each definition of MDA, a range of possible cutoff values of IGA × BSA was examined at each time point. The optimal cutoff value was determined using Youden index (YI), calculated as (sensitivity + specificity – 1). Results: For MDA defined as PASI 90 and DLQI 0/1, optimal IGA × BSA cutoffs were 2.10 at week 12 (YI, 0.60; sensitivity, 0.78; specificity, 0.82), 1.02 at week 24 (YI, 0.55; sensitivity, 0.73; specificity, 0.82), and 1.00 at week 52 (YI, 0.65; sensitivity, 0.79; specificity, 0.86). For MDA defined as PASI score ≤1 or BSA <3%, optimal IGA × BSA cutoffs were 2.98 at week 12 (YI, 0.91; sensitivity, 0.99; specificity, 0.92), 2.80 at week 24 (YI, 0.94; sensitivity, 0.99; specificity, 0.95), and 3.00 at week 52 (YI, 0.96; sensitivity, 1.00; specificity, 0.96). Conclusion: IGA × BSA could be a valid measure highly associated with achievement of MDA.

Differential synovial tissue biomarkers among psoriatic arthritis and rheumatoid factor/anti-citrulline antibody-negative rheumatoid arthritis

BackgroundDifferential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Abneg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Abneg RA and test their predictive value of therapeutic response.MethodsThirty-four PsA patients [12 DMARD naive and 22 non-responder to methotrexate (MTX-IR)] with peripheral joint involvement and 55 Abneg RA (27 DMARD naive and 28 MTX-IR) underwent US-guided ST biopsy and immunohistochemistry (IHC) for CD68+, CD3+, CD20+, CD21+, CD117+, and CD138+ cells. After study entry, each DMARD-naive patient started MTX therapy and was followed in an outpatient setting for at least 6 months to define the achievement of Minimal Disease Activity (PsA) and DAS remission (Abneg RA) status respectively. Each IR-MTX patient was treated according to EULAR recommendations.ResultsAt study entry, IHC analysis revealed that PsA patients had comparable levels of lining and sublining CD68+ and sublining CD21+, CD20+, and CD3+ cells than Abneg RA, despite the therapeutic regimen. Moreover, regardless of the therapeutic scheme, PsA patients showed higher IHC score of CD117+ cells (p = 0.0004 and p = 0.0005 for naive and MTX-IR patients respectively) compared to Abneg RA patients. Conversely, Abneg RA patients showed higher IHC score of CD138+ cells, irrespective to the therapeutic scheme (p = 0.04 and p = 0.002 for naive and MTX-IR patients respectively). Analyzing the response rate to the therapeutic scheme, naive PsA patients reaching MDA status at 6 months follow-up, showed, at the study entry, lower IHC score of CD3+ cells compared to PsA patients not reaching this outcome (p = 0.02); conversely, naive Abneg RA patients reaching DAS remission status at 6 months follow-up, showed, at the study entry, lower IHC score of sublining CD68+ cells compared to Abneg RA patients not reaching this outcome (p < 0.001).ConclusionsCD117+ and CD138+ cells are differentially distributed among PsA and Abneg RA. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.