1. Posters & Abstracts from Amsterdam
Psoriatic Arthritis
Posters & Abstracts from Amsterdam

2. Efficacy and safety of ixekizumab in patients with active psoriatic arthritis: Three year results from a phase 3 study (SPIRIT-P1)

3. 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.

4. 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 in the ixekizumab Q2W group and -0.4 in the Q4W group

5. 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

6. 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

7. 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

8. Efficacy of tofacitinib by background methotrexate dose in patients with psoriatic arthritis: A post-hoc analysis of pooled data from 2 phase 3 trials

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. Underestimation of cardiovascular events by cardiovascular risk scores in psoriatic arthritis patients

16. 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

17. 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

18. 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

19. 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

20. 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

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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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.

28. 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.

29. 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

30. 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

31. 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

32. 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