Comparative Effectiveness of Bimekizumab and Guselkumab in Patients with Psoriatic Arthritis at 52 Weeks Assessed Using a Matching-Adjusted Indirect Comparison.

INTRODUCTION: Matching-adjusted indirect comparisons (MAIC) were used to assess the relative efficacy of bimekizumab 160 mg every 4 weeks (Q4W) compared to guselkumab 100 mg Q4W or every 8 weeks (Q8W) at 48/52 weeks in patients with psoriatic arthritis (PsA) who were biologic disease-modifying antirheumatic drug-naïve (bDMARD-naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR). METHODS: Relevant trials were identified as part of a systematic literature review. For patients who were bDMARD-naïve, individual patient data (IPD) from BE OPTIMAL (N = 431) was matched to summary data from DISCOVER-2 (Q4W, n = 245; Q8W, n = 248). For patients who were TNFi-IR, IPD from BE COMPLETE (n = 267) and summary data from COSMOS (Q8W, N = 189). Trial populations were re-weighted using propensity scores. Unanchored comparisons of recalculated bimekizumab and guselkumab 48- or 52-week non-responder imputation outcomes for 20/50/70% improvement in American College of Rheumatology score (ACR20/50/70) and minimal disease activity (MDA) index were analyzed. RESULTS: In patients who were bDMARD-naïve, bimekizumab was associated with a greater likelihood of ACR50 (odds ratio [95% confidence interval] 1.62 [1.07, 2.44]; p = 0.021), ACR70 (2.20 [1.43, 3.38]; p < 0.001), and MDA (1.82 [1.20, 2.76]; p = 0.005) compared to guselkumab Q4W at week 52. Bimekizumab also had a greater likelihood of ACR70 response (2.08 [1.34, 3.22]; p = 0.001) and MDA (2.07 [1.35, 3.17]; p < 0.001) compared to guselkumab Q8W at week 52. In patients who were TNFi-IR, bimekizumab had a greater likelihood in achieving all evaluated outcomes compared to guselkumab Q8W at week 48/52 (ACR20, 1.77 [1.15, 2.72]; p = 0.010; ACR50, 1.56 [1.03, 2.36]; p = 0.037; ACR70, 1.66 [1.05, 2.61]; p = 0.028; and MDA, 1.95 [1.27, 3.02]; p = 0.003). CONCLUSIONS: According to MAICs, bimekizumab demonstrated greater or comparable efficacy on ACR50/70 and MDA outcomes than guselkumab in patients with PsA who were bDMARD-naïve and TNFi-IR at week 48/52. Bimekizumab had a more favorable likelihood than guselkumab in achieving more stringent treatment outcomes. TRIAL REGISTRATIONS: NCT03895203, NCT03896581, NCT04009499, NCT03158285, NCT03796858.

Guselkumab provides durable improvement across psoriatic arthritis disease domains: post hoc analysis of a phase 3, randomised, double-blind, placebo-controlled study.

OBJECTIVE: Evaluate long-term guselkumab effectiveness across Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-recognised domains/related conditions of psoriatic arthritis (PsA). METHODS: Post hoc analyses used data from DISCOVER-2 (NCT03158285) biologic/Janus-kinase inhibitor-naïve participants with active PsA (≥5 swollen/≥5 tender joints, C-reactive protein ≥0.6 mg/dL), randomised (1:1:1) to guselkumab every 4 or 8 weeks (Q4W/Q8W) or placebo with crossover to guselkumab. Outcomes aligned with key GRAPPA-recognised domains of overall disease activity, peripheral arthritis, axial disease, enthesitis/dactylitis and skin psoriasis (nail psoriasis was not evaluated). PsA-related conditions (inflammatory bowel disease (IBD)/uveitis) were assessed via adverse events through W112. Least squares mean changes from baseline through W100 in continuous outcomes employed repeated measures mixed-effects models adjusting for baseline scores. Binary measure response rates were determined with non-responder imputation for missing data. RESULTS: 442/493 (90%) of guselkumab-randomised patients completed treatment through W100. Following early reductions in disease activity with guselkumab, durable improvements were observed across key PsA domains (swollen/tender joints, psoriasis, spinal pain, enthesitis/dactylitis) through W100. Response rates of therapeutically relevant targets generally increased through W100 with guselkumab Q4W/Q8W: Disease Activity Index for PsA low disease activity (LDA) 62%/59%, enthesitis resolution 61%/70%, dactylitis resolution 72%/83%, 100% improvement in Psoriasis Area and Severity Index 59%/53%, Psoriatic Arthritis Disease Activity Score LDA 51%/49% and minimal disease activity 38%/40%. Through W112, no cases of IBD developed among guselkumab-randomised patients and one case of uveitis was reported. CONCLUSION: In biologic-naïve patients with active PsA, guselkumab provided early and durable improvements in key GRAPPA-recognised domains through 2 years, with substantial proportions achieving important treatment targets.

EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2023 update.

OBJECTIVE: New modes of action and more data on the efficacy and safety of existing drugs in psoriatic arthritis (PsA) required an update of the EULAR 2019 recommendations for the pharmacological treatment of PsA. METHODS: Following EULAR standardised operating procedures, the process included a systematic literature review and a consensus meeting of 36 international experts in April 2023. Levels of evidence and grades of recommendations were determined. RESULTS: The updated recommendations comprise 7 overarching principles and 11 recommendations, and provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs should be used in monotherapy only for mild PsA and in the short term; oral glucocorticoids are not recommended. In patients with peripheral arthritis, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended and methotrexate preferred. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drug (bDMARD) should be initiated, without preference among modes of action. Relevant skin psoriasis should orient towards bDMARDs targeting interleukin (IL)-23p40, IL-23p19, IL-17A and IL-17A/F inhibitors. In case of predominant axial or entheseal disease, an algorithm is also proposed. Use of Janus kinase inhibitors is proposed primarily after bDMARD failure, taking relevant risk factors into account, or in case bDMARDs are not an appropriate choice. Inflammatory bowel disease and uveitis, if present, should influence drug choices, with monoclonal tumour necrosis factor inhibitors proposed. Drug switches and tapering in sustained remission are also addressed. CONCLUSION: These updated recommendations integrate all currently available drugs in a practical and progressive approach, which will be helpful in the pharmacological management of PsA.

Impact of filgotinib on pain control in the phase 3 FINCH studies.

OBJECTIVE: This post hoc analysis of the FINCH 1-3 (NCT02889796, NCT02873936 and NCT02886728) studies assessed specific effects of filgotinib on pain control and their relationship with other aspects of efficacy in patients with rheumatoid arthritis (RA). METHODS: Assessments included: residual pain responses of ≤10 and ≤20 mm on a 100 mm visual analogue scale (VAS); the proportion of patients who achieved VAS pain responses in addition to remission or low disease activity by Disease Activity Score-28 with C-reactive protein (DAS28-CRP) or Clinical Disease Activity Index (CDAI) criteria. RESULTS: Across studies, filgotinib reduced pain from week 2, with responses sustained throughout the studies. In FINCH 1, at week 24, 35.8%, 25.0%, 24.6% and 11.6% of patients in the filgotinib 200 mg, filgotinib 100 mg, adalimumab and placebo arms (each plus methotrexate) achieved VAS pain ≤20 mm in addition to DAS28-CRP remission; 26.3%, 17.9%, 17.2% and 7.6% achieved VAS pain ≤10 mm in addition to DAS28-CRP remission. A similar pattern was seen for CDAI remission. Time during which VAS pain was ≤10 or ≤20 mm was longest with filgotinib 200 mg and comparable between adalimumab and filgotinib 100 mg. Similar findings were reported for filgotinib in FINCH 2 and 3. CONCLUSION: In all RA populations studied, pain improvements occurred from week 2 and were sustained over time. In FINCH 1, filgotinib 100 mg provided similar pain amelioration to adalimumab, whereas filgotinib 200 mg resulted in greater pain improvement and higher proportion of patients with residual pain ≤10 or ≤20 mm and meeting DAS28-CRP remission criteria.

Comparative Effectiveness of Bimekizumab and Secukinumab in Patients with Psoriatic Arthritis at 52 Weeks Using a Matching-Adjusted Indirect Comparison.

INTRODUCTION: Matching-adjusted indirect comparisons (MAICs) were used to compare the efficacy of bimekizumab and secukinumab 150 mg and 300 mg at 52 weeks for the treatment of psoriatic arthritis (PsA) in patients who were biologic disease-modifying anti-rheumatic drug-naïve (bDMARD-naïve) or with previous inadequate response or intolerance to tumor necrosis factor inhibitors (TNFi-IR). METHODS: Relevant trials were systematically identified. Individual patient data from bimekizumab randomized controlled trials, BE OPTIMAL (N = 431) and BE COMPLETE (N = 267), were matched to aggregate data from bDMARD-naïve and TNFi-IR patient subgroups from FUTURE 2 using secukinumab 150 mg and 300 mg doses (bDMARD-naïve: N = 63/37; TNFi-IR: N = 67/33). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of patients in the secukinumab trials. Unanchored comparisons of recalculated bimekizumab and secukinumab 52-week non-responder imputation outcomes for 20/50/70% improvement in American College of Rheumatology score (ACR20/50/70) and minimal disease activity (MDA) index were analyzed. RESULTS: In patients who were bDMARD-naïve, bimekizumab had a greater likelihood of ACR70 response than secukinumab 150 mg (odds ratio [95% confidence interval] 2.39 [1.26, 4.53]; p = 0.008) and secukinumab 300 mg (2.03 [1.11, 3.72]; p = 0.021) at 52 weeks. In patients who were TNFi-IR, bimekizumab had a greater likelihood of response compared to secukinumab 150 mg for ACR20 (3.50 [1.64-7.49]; p = 0.001), ACR50 (3.32 [1.41, 7.80]; p = 0.006), ACR70 (2.95 [1.08, 8.07]; p = 0.035) and MDA (3.52 [1.38, 8.99]; p = 0.009), and a greater likelihood of response compared to secukinumab 300 mg for ACR50 (2.44 [1.06, 5.65]; p = 0.037) and MDA (2.92 [1.20, 7.09]; p = 0.018) at 52 weeks. CONCLUSION: In this MAIC analysis, the efficacy of bimekizumab, as demonstrated by the likelihood of ACR20/50/70 and MDA response at 52 weeks, was greater or comparable to secukinumab 150 mg and 300 mg for patients with PsA who were bDMARD-naïve and TNFi-IR. TRIAL REGISTRATION NUMBERS: NCT03895203, NCT03896581, NCT04009499, NCT01752634, NCT01989468, NCT02294227, NCT02404350.

Comparative efficacy and safety of bimekizumab in psoriatic arthritis: a systematic literature review and network meta-analysis.

OBJECTIVES: To understand the relative efficacy and safety of bimekizumab, a selective inhibitor of interleukin-17F in addition to IL-17A, vs other biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) for psoriatic arthritis (PsA) using network meta-analysis (NMA). METHODS: A systematic literature review (most recent update conducted on 01 January 2023) identified randomised controlled trials (RCTs) of b/tsDMARDs in PsA. Bayesian NMAs were conducted for efficacy outcomes at Weeks 12-24 for b/tsDMARD-naïve and tumour necrosis factor inhibitor (TNFi) -experienced (exp) patients. Safety at Weeks 12-24 was analysed in a mixed population. Odds ratios (ORs) and differences of mean change with the associated 95% credible interval (CrI) were calculated for the best-fitting models, and the surface under the cumulative ranking curve (SUCRA) values were calculated to determine relative rank. RESULTS: The NMA included 41 RCTs for 22 b/tsDMARDs. For minimal disease activity (MDA), bimekizumab ranked 1st in b/tsDMARD-naïve patients and 2nd in TNFi-exp patients. In b/tsDMARD-naïve patients, bimekizumab ranked 6th, 5th, and 3rd for American College of Rheumatology response (ACR)20/50/70, respectively. In TNFi-experienced patients, bimekizumab ranked 1st, 2nd, and 1st for ACR20/50/70, respectively. For Psoriasis Area and Severity Index [PASI]90/100, bimekizumab ranked 2nd and 1st in b/tsDMARD-naïve patients, respectively, and 1st and 2nd in TNFi-exp patients, respectively. Bimekizumab was comparable to b/tsDMARDs for serious adverse events. CONCLUSION: Bimekizumab ranked favourably among b/tsDMARDs for efficacy on joint, skin, and MDA outcomes, and showed comparable safety, suggesting it may be a beneficial treatment option for patients with PsA.

Systematic literature review and network meta-analysis of therapies for psoriatic arthritis on patient-reported outcomes.

OBJECTIVES: Head-to-head clinical trials are common in psoriasis, but scarce in psoriatic arthritis (PsA), making treatment comparisons between therapeutic classes difficult. This study describes the relative effectiveness of targeted synthetic (ts) and biologic (b) disease-modifying antirheumatic drugs (DMARDs) on patient-reported outcomes (PROs) through network meta-analysis (NMA). DESIGN: A systematic literature review (SLR) was conducted in January 2020. Bayesian NMAs were conducted to compare treatments on Health Assessment Questionnaire Disability Index (HAQ-DI) and 36-item Short Form (SF-36) Health Survey including Mental Component Summary (MCS) and Physical Component Summary (PCS) scores. DATA SOURCES: Ovid MEDLINE (including Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily),Embase and Cochrane Central Register of Controlled Trials. ELIGIBILITY CRITERIA: Phase III randomised controlled trials (RCTs) evaluating patients with PsA receiving tsDMARDS, bDMARDs or placebo were included in the SLR; there was no restriction on outcomes. DATA EXTRACTION AND SYNTHESIS: Two independent researchers reviewed all citations. Data for studies meeting all inclusion criteria were extracted into a standardised Excel-based form by one reviewer and validated by a second reviewer. A third reviewer was consulted to resolve any discrepancies, as necessary. Risk of bias was assessed using the The National Institute for Health and Care Excellence clinical effectiveness quality assessment checklist. RESULTS: In total, 26 RCTs were included. For HAQ-DI, SF-36 PCS and SF-36 MCS scores, intravenous tumour necrosis factor (TNF) alpha inhibitors generally ranked higher than most other classes of therapies available to treat patients with PsA. For almost all outcomes, several interleukin (IL)-23, IL-17A, subcutaneous TNF and IL-12/23 agents offered comparable improvement, while cytotoxic T-lymphocyte-associated antigen 4, phosphodiesterase-4 and Janus kinase inhibitors often had the lowest efficacy. CONCLUSIONS: While intravenous TNFs may provide some improvements in PROs relative to several other tsDMARDs and bDMARDs for the treatment of patients with PsA, differences between classes of therapies across outcomes were small.

MACE and VTE across upadacitinib clinical trial programmes in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis.

OBJECTIVES: To provide an integrated analysis of major adverse cardiovascular events (MACEs) and events of venous thromboembolism (VTE) and associated risk factors across rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) phase 2b/3 upadacitinib clinical programmes. METHODS: Data were analysed and summarised from clinical trials of RA, PsA and AS treated with upadacitinib 15 mg once daily (QD) and 30 mg QD (as of 30 June 2021). Data from adalimumab (RA and PsA) and methotrexate (RA) arms were included as comparators. Adjudicated MACEs and VTE events were presented as exposure-adjusted rates per 100 patient-years (E/100 PY). Univariable Cox proportional hazard regression analyses assessed potential associations of risk factors for MACE and VTE. RESULTS: In total, 4298 patients received upadacitinib 15 mg (RA n=3209, PsA n=907 and AS n=182) and 2125 patients received upadacitinib 30 mg (RA n=1204 and PsA n=921). In patients with RA and PsA, rates of MACE (0.3-0.6 E/100 PY) and VTE (0.2-0.4 E/100 PY) were similar across upadacitinib doses; in patients with AS, no MACEs and one VTE event occurred. Most patients experiencing MACEs or VTE events had two or more baseline cardiovascular risk factors. Across RA and PsA groups, rates of MACEs and VTE events were similar. CONCLUSIONS: Rates of MACEs and VTE events with upadacitinib were consistent with previously reported data for patients receiving conventional synthetic and biologic disease-modifying anti-rheumatic drugs and comparable with active comparators adalimumab and methotrexate. Associated patient characteristics are known risk factors for MACEs and VTE events. TRIAL REGISTRATION NUMBERS: RA (SELECT-NEXT: NCT02675426; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847; SELECT-COMPARE: NCT02629159; SELECT-EARLY: NCT02706873, SELECT-CHOICE: NCT03086343), PsA (SELECT-PsA 2: NCT03104374; SELECT-PsA 1: NCT03104400), and AS (SELECT-AXIS 1: NCT03178487).

Proceedings of the GRAPPA 2022 Executive Retreat.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) leadership congregated for a strategic planning meeting before the 2022 GRAPPA annual meeting in New York, USA. Meeting aims were to review GRAPPA's performance in relation to its 2016 goals and identify successes and areas for further improvement, identify key GRAPPA priorities and activities for the next 5 years, and explore committee structures to best support these aims.

Impact of COVID-19 on Patients With Psoriasis or Psoriatic Arthritis.

Given the impact of the coronavirus disease 2019 (COVID-19) on patients with psoriatic disease (PsD), a session was devoted at the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2022 annual meeting to discussing the current understanding of the risk of severe COVID-19 in patients with PsD. The effects of PsD and its treatment on prevention and treatment of COVID-19 with vaccinations, antiviral drugs, and monoclonal antibodies were discussed. The session concluded with a presentation on the perspectives of patient research partners about their experiences with COVID-19.

The effect of ixekizumab on axial manifestations in patients with psoriatic arthritis from two phase III clinical trials: SPIRIT-P1 and SPIRIT-P2.

Background: Psoriatic arthritis (PsA) is a chronic inflammatory condition predominantly affecting the peripheral joints. However, some patients with PsA can experience axial involvement which is manifested with back pain and associated with increased burden of illness. Objectives: The aim of this post hoc analysis was to determine the efficacy of ixekizumab (IXE) up to 52 weeks in reducing axial symptoms in PsA patients, presenting with axial manifestations. Design: This was a post hoc analysis of two pooled phase III clinical trials. Methods: Patients with axial manifestations, from two placebo-controlled, randomized, double-blind, phase III trials (SPIRIT-P1 and SPIRIT-P2), were defined as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 (Q2; back pain)] total score ⩾4 and average of BASDAI Q5 + Q6 (morning stiffness) ⩾4 at baseline. For this post hoc analysis, the efficacy of IXE was evaluated at weeks 16, 24, and 52 using separate BASDAI questions (including back pain and morning stiffness), total BASDAI and modified BASDAI (mBASDAI; without Q3), Ankylosing Spondylitis Disease Activity Score (ASDAS), and 50% improvement in BASDAI (BASDAI50) response. Treatment comparisons were performed using logistic regression and analysis of covariance model for categorical and continuous end points, respectively. Results: In the post hoc analysis among PsA patients with axial manifestations at baseline (N = 313), improvements in back pain and morning stiffness at weeks 16 and 24 were significantly greater in patients receiving IXE versus placebo (both p < 0.001). Improvements in BASDAI individual scores and total scores, mBASDAI, and ASDAS were significantly greater in patients receiving IXE compared with placebo. Similarly, significantly more IXE-treated patients achieved BASDAI50 at weeks 16 and 24 versus placebo. The effect of IXE was sustained at week 52. Similar effects were observed in sensitivity analyses subgroups. Conclusion: IXE is effective in improving axial symptoms in patients with active PsA presenting with axial manifestations.

Ixekizumab improves symptoms of back pain and morning stiffness in patients with psoriatic arthritis Background: Psoriatic arthritis is a chronic, immune-mediated condition with heterogeneous manifestations including peripheral arthritis, axial arthritis, enthesitis, dactylitis, and skin and nail psoriasis. Some patients with psoriatic arthritis also experience symptoms relating to the spine and sacroiliac joint. These symptoms are referred to as axial manifestations of the psoriatic arthritis. Ixekizumab is a monoclonal antibody that targets IL-17A with high affinity. IL-17A has been implicated in the pathogenesis of PsA. Aim: The aim is to investigate the effects of ixekizumab in controlling symptoms suggestive of axial involvement in patients with active psoriatic arthritis. Methods: This post hoc analysis included patients with psoriatic arthritis from two phase III clinical trials. Only patients with psoriatic arthritis who had back pain and morning stiffness at baseline were included. In the second analysis, we assessed the effect of ixekizumab in a subset of patients with psoriatic arthritis with back pain who were aged less than 45 years. A third analysis included a subset of patients with increased CRP. Results: Our results show that patients with psoriatic arthritis and back pain suggestive of axial involvement experience a greater disease burden than patients without back pain. This post hoc analysis showed that ixekizumab was significantly better compared with placebo in improving inflammatory back pain, morning stiffness, and disease activity at weeks 16 and 24. Disease activity was also significantly improved in ixekizumab-treated patients compared with placebo. Conclusion: Axial manifestations in patients with psoriatic arthritis were significantly improved following ixekizumab treatment. These improvements were noted regardless of whether the patients were less than 45 years and regardless of the level of inflammation.

A Comprehensive Review of Ixekizumab Efficacy in Nail Psoriasis from Clinical Trials for Moderate-to-Severe Psoriasis and Psoriatic Arthritis.

Nail psoriasis is a difficult-to-treat manifestation of psoriatic disease affecting up to 80% of patients with psoriatic arthritis (PsA) and 40-60% of patients with plaque psoriasis (PsO). Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-17A, is approved for the treatment of patients with PsA and patients with moderate-to-severe PsO. This narrative review aims to summarize nail psoriasis data generated from IXE clinical trials in patients with PsA (SPIRIT-P1, SPIRIT-P2, and SPIRIT-H2H) and/or moderate-to-severe PsO (UNCOVER-1, -2, -3, IXORA-R, IXORA-S, and IXORA-PEDS) with an emphasis on head-to-head clinical trial data. Across numerous trials explored, IXE treatment was associated with greater improvement in resolution of nail disease versus comparators at week 24, results which were maintained up to and beyond week 52. Additionally, patients experienced higher rates of resolution of nail disease versus comparators at week 24 and maintained high levels of resolution up to week 52 and beyond. In both PsA and PsO, IXE demonstrated efficacy in treating nail psoriasis, and therefore may be an effective therapy option. Trial Registration: ClinicalTrials.gov identifier UNCOVER-1 (NCT01474512), UNCOVER-2 (NCT01597245), UNCOVER-3 (NCT01646177), IXORA-PEDS (NCT03073200), IXORA-S (NCT02561806), IXORA-R (NCT03573323), SPIRIT-P1 (NCT01695239), SPIRIT-P2 (NCT02349295), SPIRIT-H2H (NCT03151551).

Australian consensus: Treatment goals for moderate to severe psoriasis in the era of targeted therapies - Adult patients.

BACKGROUND: Over the last decade, the treatment landscape for moderate-severe psoriasis has rapidly evolved. The Australasian College of Dermatologists sought to review and update previously published treatment goals for moderate-severe psoriasis. METHODS: A modified Delphi approach was used. Comprehensive literature review and guideline evaluation resulted in the development of statements and other questions to establish current clinical practices. Two rounds of anonymous voting were undertaken, with a collaborative meeting held in between to discuss areas of discordance. Overall, consensus was defined as achievement of ≥75% agreement in the range 7-9 on a 9-point scale (1 strongly disagree; 9 strongly agree). RESULTS: Consensus was achieved on 26/29 statements in round 1 and a further 20 statements in round 2. There was strong agreement to expanding the classification/definition of psoriasis severity by including a choice of metrics, incorporating quality of life measures, and widening the scope of high-impact sites. Consensus was also reached on revised treatment response criteria, which were then incorporated into a new treatment algorithm. There was discordance with the current requirement to undertake a trial with established systemic agents before accessing targeted therapy. CONCLUSION: The ability of new targeted treatment options to change the narrative in psoriasis patient care can only be properly realised if challenges to timely and equitable access are addressed. The proposed framework for the assessment, classification and management of moderate-severe psoriasis aligns with international recommendations. Its adoption into Australian clinical practice is hoped to improve treatment outcomes and patients' satisfaction with their care.

Long-Term Durability of Certolizumab Pegol in Patients with Rheumatoid Arthritis Over 5 Years: An Analysis of Pooled Clinical Trial Data.

INTRODUCTION: There is a paucity of data on how patient characteristics may affect the long-term durability of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA). This study therefore aimed to investigate CZP durability and reasons for discontinuation over 5 years between different subgroups of patients with RA. METHODS: Data were pooled from 27 clinical trials in RA patients. Durability was defined as the percentage of patients randomized to CZP at baseline who were still on CZP treatment at a given timepoint. Post hoc analyses of clinical trial data on CZP durability and reasons for discontinuation among different patient subgroups were conducted using Kaplan-Meier curves and Cox proportional hazards modeling. Patient subgroups included: age (18- < 45/45- < 65/ ≥ 65 years), gender (male/female), prior tumor necrosis factor inhibitor (TNFi) use (yes/no), and disease duration (< 1/1- < 5/5- < 10/ ≥ 10 years). RESULTS: Among 6927 patients, the durability of CZP was 39.7% at 5 years. Patients aged ≥ 65 years had a 33% greater risk of CZP discontinuation than patients 18- < 45 years (hazard ratio [95% confidence interval]: 1.33 [1.19-1.49]) and patients with prior TNFi use had a 24% greater risk of discontinuing CZP than patients without (1.24 [1.12-1.37]). Conversely, greater durability was observed among patients who had a baseline disease duration of ≥ 1 year. Durability did not differ in the gender subgroup. Of the 6927 patients, the most common reason for discontinuation was inadequate levels of efficacy (13.5%); followed by adverse events (11.9%); consent withdrawn (6.7%); lost to follow-up (1.8%); protocol violation (1.7%); other reasons (9.3%). CONCLUSIONS: CZP durability was comparable with durability data on other bDMARDs in RA patients. Patient characteristics that were associated with greater durability included younger age, TNFi-naïvety, and disease duration ≥ 1 year. Findings may be helpful in informing clinicians on a patient's likelihood of discontinuing CZP, based on their baseline characteristics.

Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis.

OBJECTIVE: To evaluate the long-term safety profile for upadacitinib across rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and atopic dermatitis (AD). METHODS: Safety data from clinical trials of upadacitinib 15 mg and upadacitinib 30 mg (AD only) for treating RA, PsA, AS and AD as of 30 June 2021 were analysed; some RA and PsA studies included adalimumab and methotrexate as active comparators. Treatment-emergent adverse events (TEAEs) were presented by disease as exposure-adjusted event rates per 100 patient years (E/100 PY). RESULTS: The analysis included 6991 patients (RA, n=3209; PsA, n=907; AS, n=182; AD, n=2693) who received at least one dose of upadacitinib, representing 15 425 PY of exposure (maximum duration 2.75-5.45 years) across diseases. Rates (E/100 PY) of any TEAE (205.5-278.1) and TEAE leading to discontinuation (4.5-5.4) were similar across diseases; serious TEAEs were numerically higher in patients with RA and PsA. Rates of herpes zoster (1.6-3.6), non-melanoma skin cancer (0-0.8) and elevations in creatine phosphokinase levels (4.4-7.9) were higher with upadacitinib than with active comparators in the RA and PsA populations. Deaths (0-0.8), serious infections (0-3.9), major adverse cardiovascular events (0-0.4), venous thromboembolism (<0.1-0.4) and malignancies (0.3-1.4) were observed, with rates generally lowest in AS and AD. Increased rates of acne were observed in patients with AD only. CONCLUSIONS: Findings from this analysis demonstrate that upadacitinib is generally well tolerated with observed differences in safety profiles likely reflective of varying patient characteristics across RA, PsA, AS and AD populations. TRIAL REGISTRATION NUMBERS: NCT02675426, NCT02706951, NCT02706847, NCT02629159, NCT02706873, NCT03086343, NCT03104374, NCT03104400, NCT03178487, NCT03569293, NCT03568318 and NCT03607422.

Etanercept Withdrawal and Retreatment in Nonradiographic Axial Spondyloarthritis: Results of RE-EMBARK, an Open-Label Phase IV Trial.

OBJECTIVE: RE-EMBARK investigated etanercept (ETN) withdrawal and retreatment in patients with nonradiographic axial spondyloarthritis (nr-axSpA) achieving inactive disease. METHODS: Patients received ETN and a background nonsteroidal antiinflammatory drug for 24 weeks in period 1 (P1); those achieving inactive disease (Ankylosing Spondylitis Disease Activity Score [ASDAS] with C-reactive protein [CRP] < 1.3) discontinued ETN for 40 weeks or less (period 2 [P2]). Patients who flared (ASDAS with erythrocyte sedimentation rate [ESR] ≥ 2.1) were retreated for 12 weeks in period 3 (P3). The primary endpoint was the proportion of patients with inactive disease who flared within 40 weeks of ETN withdrawal. Baseline characteristics were analyzed post hoc as predictors of maintenance and regaining of inactive disease, respectively, using univariate logistic and stepwise multivariable logistic regression models. RESULTS: The proportion of patients experiencing flare following ETN withdrawal (P2) increased from 22.3% (25/112) after 4 weeks to 67% (77/115) after 40 weeks; 74.8% (86/115) experienced flare at any time during P2. Median time to flare was 16.1 weeks. Most patients (54/87, 62.1%) who were retreated with ETN in P3 reachieved inactive disease. Absence of both sacroiliitis detected on magnetic resonance imaging (MRI) and high-sensitivity CRP (hs-CRP) > 3 mg/L at baseline predicted inactive disease maintenance in P2 following ETN withdrawal in multivariable analysis; male sex and age younger than 40 years predicted regaining of inactive disease in P3 after flare/retreatment. There were no unexpected safety signals. CONCLUSION: Approximately 25% of patients maintained inactive disease for 40 weeks after discontinuing ETN. Absence of both MRI sacroiliitis and high hs-CRP at baseline predicted response maintenance after ETN withdrawal. (ClinicalTrials.gov: NCT02509026).