Posters & Abstracts from Amsterdam Psoriatic Arthritis Posters & Abstracts from Amsterdam

Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: Three year results from a phase 3 study (SPIRIT-P1) http://scientific.sparx-ip.net/archiveeular/?c=a&searchfor=chandran&view=1&item=2018THU0333

Study Design and Methods This reports the results of the extension phase of the 24-week SPIRIT-P1 study SPIRIT-O1: 417 biologic-naïve patients were randomized to ixekizumab every 2 or 4 weeks or placebo At 24 weeks, ixekizumab was superior to placebo in improving the signs and symptoms of PsA. ACR 20 response (primary endpoint) at 24 weeks was observed in 58% and 62% of patients treated with ixekizumab 200 mg or 400 mg, respectively, and 30% of patients treated with placebo. 381 patients entered the extension phase Patients failing to demonstrate ≥20% improvement in both tender and swollen joint counts at week 32, or any subsequent visit, were discontinued from the study.

Results Summary 125 of the 210 patients (60%) initially randomized to ixekizumab at week 0 completed 156 weeks of treatment At week 156, the following responses were observed in the ixekizumab Q2W and Q4W ITT groups, respectively: ACR20 in 62% and 69% ACR70 in 44% and 33% Psoriasis Area and Severity Index (or PASI) 75 in 69% and 63% PASI100 in 61% and 44% Leeds Enthesitis Index = 0 in 40% and 47% Leeds Dactylitis Index = 0 in 69% and 62% Mean change from baseline in the Health Assessment Questionnaire Disability Index was -0.5 in the ixekizumab Q2W group and -0.4 in the Q4W group

Results Summary (cont) In the extension phase A treatment-emergent adverse event was observed in 76% of patients each in the ixekizumab Q2W and Q4W groups The majority of treatment-emergent adverse events were mild or moderate in severity A serious adverse event occurred in 10% and 15% of patients treated with ixekizumab Q2W or Q4W, respectively The most common adverse event was an infection, which was observed in 49% and 48% of ixekizumab Q2W and Q4W patients, respectively

Principal Investigator Commentary 3 important highlights or summary points from the study In patients with PsA naïve to biologic therapy, treatment with ixekizumab leads to persistent control of disease activity over a 3-year period Ixekizumab has persistent efficacy in multiple domains including peripheral arthritis, psoriasis, dactylitis, enthesitis, and function Serious adverse events and serious treatment-emergent adverse events in patients exposed to ixekizumab were seen in less than 10% of patients; no new or unusual adverse events were observed Anticipated impact of the study findings on the care of patients This study further establishes the value of IL-17 inhibition in the management of PsA and is a welcome addition to the PsA therapeutic armamentarium

Faculty Commentary Ixekizumab is an IL-17 inhibitor Three-year data show that ixekizumab is persistently active and effective at a clinically meaningful rate There were no surprises in the safety database Most important finding Impressive reductions in both enthesitis and dactylitis Enthesitis, which is seen in the majority of patients with PsA, is something in which patients are interested because these symptoms can be debilitating Ixekizumab was effective across all domains This study adds reassurance to the long-term use of ixekizumab

Efficacy of tofacitinib by background methotrexate dose in patients with psoriatic arthritis: A post-hoc analysis of pooled data from 2 phase 3 trials http://scientific.sparx-ip.net/archiveeular/?searchfor=kivitz&view=1&c=a&item=2018AB0902

Study Design and Methods Post hoc analysis of pooled data from 2 phase 3, randomized, double-blind, placebo-controlled studies of tofacitinib in patients with active PsA Patients had ≥3 swollen and ≥3 tender joints In 1 study, patients were tumor necrosis factor inhibitor-naïve and had an inadequate response to ≥1 conventional synthetic DMARDs In the other study, patients had an inadequate response to ≥1 tumor necrosis factor inhibitor Patients were randomized to Tofacitinib 5 or 10 mg twice daily Placebo Adalimumab 40 mg every 2 weeks

Study Design and Methods (cont) All patients received stable doses of 1 conventional synthetic DMARD as background therapy The maximum dose of methotrexate was 20 mg/week

Results Summary Analysis included 556 patients who received tofacitinib plus methotrexate only or placebo plus methotrexate only Two-thirds were treated with a background methotrexate dose ≤15 mg/week; mean dose 12.6 mg/week One-third were treated with a background methotrexate dose >15 mg/week; mean methotrexate dose of 19.8 mg/week At month 3, tofacitinib 5 mg and 10 mg twice daily were generally associated with numerically greater American College of Rheumatology response rate Health Assessment Questionnaire- Disability Index (HAQ-DI) response rate Changes from baseline in HAQ-DI score compared with placebo

Results Summary (cont) The magnitude of tofacitinib effects on efficacy outcomes were broadly similar in patients with background methotrexate dose ≤15 mg/week compared with >15 to 20 mg/week ACR 20 response rates Tofacitinib 5 mg twice daily: 47% for methotrexate ≤15 mg/week vs 51% for methotrexate >15 mg/week Tofacitinib 10 mg twice daily: 55% for methotrexate ≤15 mg/week vs 52% for methotrexate >15 mg/week Decrease ≥0.35 in the HAC-DI response rate Tofacitinib 5 mg twice daily: 48% for methotrexate ≤15 mg/week vs 56% treated with methotrexate >15 mg/week Tofacitinib 10 mg twice daily: 52% for methotrexate ≤15 mg/week vs 43% treated with methotrexate >15 mg/week

Principal Investigator Commentary Tofacitinib was more efficacious than placebo in patients with PsA Results did not differ for background MTX dose ≤15 or >15 mg/week Results are similar to those observed in patients with rheumatoid arthritis For care of patients, the study suggests that patients on lower doses of MTX for whatever reason can do as well as those on higher doses

Faculty Commentary We have patients with psoriatic arthritis who are candidates for advanced therapy One consideration is background MTX therapy This study shows quite clearly that, at least within the confines of MTX ≤15 vs >15 mg/wk (maximum 20 mg/wk), considering MTX dose is not a variable that warrants clinical concern. This encourages the use tofacitinib in patients on methotrexate regardless of the dose

Underestimation of cardiovascular events by cardiovascular risk scores in psoriatic arthritis patients http://scientific.sparx-ip.net/archiveeular/?c=a&searchfor=underestimation%20of%20cardiovascular%20events&view=1&item=2018SAT0309

Study Design and Methods Prospectively collected data from 2 Hong Kong cohorts of patients with PsA were used The discriminatory ability to predict cardiovascular risk was estimated by the area under the receiver operating characteristic curve Four different cardiovascular disease risk scores, and their EULAR modified versions, were calculated at baseline Framingham risk score QRISK II HeartScore American College of Cardiology/American Heart Association 10-year atherosclerotic cardiovascular disease risk score EULAR recommends multiplying these risk scores by 1.5 for patients with rheumatoid arthritis

Study Design and Methods (cont) The primary outcome was first cardiovascular event, which included a wide variety of events such as myocardial infarction, angina, stroke, heart failure, coronary artery bypass graft surgery, implantation of a pacemaker or defibrillator, among others

Results Summary 228 patients were recruited between 2006 and 2016 Mean age 48.9 years; 54% male Over a mean follow up of 6.7 years, 30 patients experienced a cardiovascular event Baseline data were available to calculate the Framingham, QRISK II, Heart Score, and ACC/AHA risk scores in 227, 226, 226, and 188 patients, respectively At baseline, those who went on to experience a cardiovascular event were significantly older had a higher prevalence of diabetes had higher systolic blood pressure had higher triglyceride level had significantly higher risk scores However, many were not identified as high risk

Results Summary (cont) Of patients who suffered a CV event, patients identified as high risk at baseline Framingham 63% QRISK II 20% HeartScore 13% ACC/AHA 46% Applying the EULAR recommended multiplication factor Framingham 80% QRISK II 36% HeartScore 27% ACC/AHA 57% These findings demonstrate that the 4 risk scores utilized in this study significantly underestimate cardiovascular risk among patients with PsA

Faculty Commentary Important study Limitations Small study Broad inclusion criteria beyond major adverse cardiovascular events EULAR multiplication factor of 1.5 recommended primarily for patients with moderate- severe rheumatoid arthritis Did including PsA patients with milder disease affect results? Risk partitioning

Implications for Clinical Practice Important to screen all patients with PsA and other inflammatory rheumatic diseases for cardiovascular disease

Probability and impact of achieving low disease activity or remission in patients with psoriatic arthritis treated with apremilast: Pooled analysis of the PALACE 1-3 phase 3 trials http://scientific.sparx-ip.net/archiveeular/?searchfor=probability%20and%20impact%20of%20achieving&view=1&c=a&item=2018AB0927

Study Design and Methods Pooled analyses of PALACE 1-3 were performed of patients assigned to treatment with apremilast 30 mg twice daily To be eligible, patients had to complete 52 weeks of treatment and have components of the clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score available Patients were grouped according to cDAPSA categories at week 52 Remission ≤4 Low disease activity >4 to ≤13 Moderate disease activity >13 to ≤27 High disease activity >27

Results Summary 374 patients were included Means of baseline cDAPSA scores ≤41 were associated with achieving moderate or low disease activity and remission at week 52 Patients in the high disease activity group at baseline had a 42% chance of achieving moderate disease activity 24% chance of achieving low disease activity 5% chance of achieving remission at week 52 Patients in the moderate disease activity group at baseline had a 41% chance of achieving low disease activity 12% chance of achieving remission at week 52 Patients in the low disease activity group at baseline had a 20% chance of achieving remission at week 52

Results Summary (cont) Similar trends were observed based upon response at week 16 Patients with moderate disease activity at week 16 had a 38% chance of achieving low disease activity 2% chance of achieving remission at week 52 Achieving cDAPSA low disease activity or remission at week 52 was associated with residual disease activity Swollen joint 1.2 vs 0.24 Tender joint 2.6 vs 0.52 Dactylitis 0.47 vs 0 Removing patients with high disease activity at baseline suggested that a mean cDAPSA 21 was associated with achieving low disease activity or remission at week 52, corresponding to a mean of 5.5 swollen joints and 9 tender joints at baseline

Principal Investigator Commentary 3 important highlights or summary points from the study We now need to look to the kinds of patient most likely to benefit from use of apremilast given its safety profile which appears favorable Subcategorization of patients with milder disease might be a sensible choice for this kind of approach Anticipated impact of the study findings on the care of patients Better selection of patients most likely to benefit from apremilast

Faculty Commentary I divide patients with PsA into 4 groups Bad joints, bad skin Bad joints, mild skin Mild joints, bad skin Mild joints, mild skin I like apremilast in particular for patients with mild joints and mild skin disease Apremilast is an oral drug which requires very little therapeutic monitoring. If patients can get through the initial phase of tolerability, there is a very low dropout rate.

Implications for Clinical Practice Patients with PsA on the milder end of the spectrum are going to be the most robust responders. This does not mean that patients with more severe disease don't respond, but if I had to pick the sweet spot for apremilast in PsA, this is what it has done for me.

Secukinumab demonstrates a consistent safety profile with up to 5 years treatment in patients with psoriatic arthritis and moderate to severe plaque psoriasis: Updated pooled safety analyses http://scientific.sparx-ip.net/archiveeular/?c=a&searchfor=mease&view=1&item=2018THU0325

Study Design and Methods Pooled data from 3 phase 3 studies involving patients with moderate to severe PsA 15 phase 3 studies involving patients with moderate to severe psoriasis Different doses of secukinumab were utilized among the studies A loading dose was administered Intravenously at doses up to 10 mg/kg or Subcutaneously at doses ranging from 75 to 300 mg The maintenance dose was 300, 150, or 75 mg administered subcutaneously Patients initially randomized to placebo were randomized to secukinumab at 12 to 24 weeks depending on study design Analyses included all patients who received at least 1 dose of secukinumab

Results Summary A total of 1380 patients with PsA representing 3867 patient-years were included in the study Also included were a total of 5181 patients with psoriasis representing 10,417 patient-years A serious adverse event occurred at an exposure-adjusted incident rate of 7.9 per 100 patient-years in patients with PsA In patients with psoriasis, the exposure-adjusted incident rate was 6.9 per 100 patient-years The most frequently reported adverse event was a viral upper respiratory tract infection PsA: exposure-adjusted incident rate of 12.1 per 100 patient-years Psoriasis: exposure-adjusted incident rate of 21.0 per 100 patient-years Exposure-adjusted incident rates for serious infections, Candida infections, inflammatory bowel disease, and major adverse cardiac events were low and similar in patients with psoriatic arthritis and psoriasis. No cases of tuberculosis were reported

Faculty Commentary IL-17 inhibitors, including secukinumab, have a low incidence of serious opportunistic infections Mucocutaneous candidiasis occurred in a small percentage of patients and was not serious Inflammatory bowel disease occurred in a small percentage of patients The results of this study reaffirm the safety of secukinumab for PsA and psoriasis