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Abstract Introduction Patients with psoriasis (PSO) and psoriatic arthritis (PsA) may frequently switch biologic therapies over the course of treatment because of symptom variability and individual responses. Real-world studies analyzing patient characteristics and clinical factors associated with biologic switching are limited. Methods This longitudinal cohort study used real-world data from the CorEvitas Psoriasis Registry to evaluate the relationship between associated disease factors and biologic switching among patients with PSO and PsA in the United States (US) and Canada following initiation of a biologic. Patients were evaluated between April 2015–August 2022. Combinations of disease severity (as measured by Psoriasis Area Severity Index [PASI]) and Dermatology Life Quality Index (DLQI) as a measure of health-related quality of life (HRQoL) were assessed, and the association with time to switching was calculated using Cox proportional hazards regression modeling. Results Among 2580 patient-initiations (instances of patients initiating a biologic), 504 (19.5%) switched biologics within 30 months of initiation. Switching was more frequent when either PASI > 10 or DLQI > 5 compared with PASI ≤ 10 or DLQI ≤ 5 at follow-up. Patients with higher skin involvement (PASI > 10) and impact on HRQoL (DLQI > 5) were 14 times more likely to switch (hazard ratio = 14.2, 95% confidence interval: 10.7, 18.9) than those with lower skin involvement (PASI ≤ 10) and HRQoL (DLQI ≤ 5). Conclusions Patients with PSO and PsA treated in a real-world dermatology setting with substantial disease factors following biologic initiation were more likely to switch therapies. Those with PASI > 10 and DLQI > 5 switched more frequently than those with PASI ≤ 10 and DLQI ≤ 5.

Abstract Introduction Psoriatic arthritis (PsA) is a chronic inflammatory disease requiring long-term treatment. Bimekizumab, a monoclonal IgG1 antibody that selectively inhibits interleukin (IL)-17F in addition to IL-17A, has demonstrated tolerability and sustained clinical efficacy for up to 1 year for patients with PsA. Here, we report the longer-‍term safety and efficacy of bimekizumab up to 2 years. Methods BE OPTIMAL (biologic disease-modifying antirheumatic drug [bDMARD]-naïve) and BE COMPLETE (prior inadequate response/intolerance to tumor necrosis factor inhibitors [TNFi-IR]) assessed subcutaneous bimekizumab 160 mg every 4 weeks in patients with PsA. BE OPTIMAL included a reference arm (adalimumab 40 mg every 2 weeks); patients switched to bimekizumab at week 52 with no washout between treatments. BE OPTIMAL week 52 and BE COMPLETE week 16 completers were eligible for the BE VITAL open-label extension. Efficacy outcomes are reported to week 104/100 (BE OPTIMAL/BE COMPLETE). Results A total of 710/852 (83.3%) bDMARD-naïve and 322/400 (80.5%) TNFi-IR patients completed week 104/100. Up to 104 weeks, patients treated with bimekizumab in BE OPTIMAL and BE COMPLETE had treatment-emergent adverse event incidence rates (exposure-adjusted incidence rate/100 patient-years) of 179.9 (95% CI 166.9, 193.7) and 100.3 (89.2, ‍112.4), respectively. The proportion of patients achieving efficacy outcomes (≥ 50% improvement from baseline in American College of Rheumatology [ACR] response criteria, 100% improvement from baseline in Psorisis Area and Severity Index [PASI], minimal disease activity [MDA]) was sustained in all patients from week 52 to week 104/100. Conclusions Bimekizumab was well tolerated for up to 2 years of treatment and no new safety signals were observed. Sustained clinical efficacy was observed up to 2 years in bDMARD-naïve and TNFi-IR patients with active PsA. Patients switching from adalimumab to bimekizumab demonstrated further improvement in skin and nail symptoms, and sustained efficacy in joint symptoms. Trial Registration BE OPTIMAL (NCT03895203), BE COMPLETE (NCT03896581), BE VITAL (NCT04009499).

Abstract Introduction A matching-adjusted indirect comparison (MAIC) was conducted to assess the relative efficacy at 52 weeks (Wk52) of bimekizumab 160 mg every 4 weeks (Q4W) and ustekinumab 45 or 90 mg every 12 weeks (Q12W) in patients with psoriatic arthritis (PsA) who were biologic disease-modifying anti-rheumatic drug naïve (bDMARD naïve) or who had a previous inadequate response or an intolerance to tumor necrosis factor inhibitors (TNFi-IR). Methods Relevant trials were systematically identified. Individual patient data from the bimekizumab trials BE OPTIMAL (NCT03895203; N = 431) and BE COMPLETE (NCT03896581; N = 267) were matched with summary data on patients receiving ustekinumab in the PSUMMIT 1 trial (NCT01009086; 45 mg, N = 205; 90 mg; N = 204) and a subgroup of TNFi-IR patients receiving ustekinumab in the PSUMMIT 2 trial (NCT01077362; 45 mg, N = 60; 90 mg, N = 58), respectively. Patients from the bimekizumab trials were re-weighted using propensity scores to match the baseline characteristics of the ustekinumab trial patients. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Non-placebo-adjusted comparisons of recalculated bimekizumab and ustekinumab outcomes for the American College of Rheumatology (ACR) 20/50/70 response criteria (non-responder imputation) were analyzed. Results In patients who were bDMARD naïve, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (odds ratio [95% confidence interval] 45 mg: 2.14 [1.35, 3.40]; 90 mg: 1.98 [1.24, 3.16]), ACR50 (45 mg: 2.74 [1.75, 4.29]; 90 mg: 2.29 [1.48, 3.55]), and ACR70 (45 mg: 3.33 [2.04, 5.46]; 90 mg: 3.05 [1.89, 4.91]). In patients who were TNFi-IR, bimekizumab had a greater likelihood of response than ustekinumab at Wk52 for ACR20 (45 mg: 4.17 [2.13, 8.16]; 90 mg: 4.19 [2.07, 8.49]), ACR50 (45 mg: 5.00 [2.26, 11.05]; 90 mg: 3.86 [1.70, 8.79]), and ACR70 (45 mg: 9.85 [2.79, 34.79]; 90 mg: 6.29 [1.98, 20.04]). Conclusions Using MAIC, bimekizumab showed greater efficacy than ustekinumab in achieving all ACR responses in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52. Trial Registration NCT03895203, NCT03896581, NCT01009086, NCT01077362.

Abstract Introduction The relative efficacy of bimekizumab and risankizumab in patients with PsA 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) was assessed at 52 weeks (Wk52) using matching-adjusted indirect comparisons (MAIC). Methods Relevant trials were systematically identified. For patients who were bDMARD naïve, individual patient data (IPD) from BE OPTIMAL (NCT03895203; N = 431) were matched with summary data from KEEPsAKE-1 (NCT03675308; N = 483). For patients who were TNFi-IR, IPD from BE COMPLETE (NCT03896581; N = 267) were matched with summary data from the TNFi-IR patient subgroup in KEEPsAKE-2 (NCT03671148; N = 106). To adjust for cross-trial differences, patients from the bimekizumab trials were re-weighted to match the baseline characteristics of patients in the risankizumab trials. Adjustment variables were selected based on expert consensus (n = 5) and adherence to established MAIC guidelines. Recalculated bimekizumab Wk52 outcomes for American College of Rheumatology (ACR) 20/50/70 response criteria and minimal disease activity (MDA) index (non-responder imputation) were compared with risankizumab outcomes via non-placebo-adjusted comparisons. Results In patients who were bDMARD naïve, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR50 (odds ratio [95% confidence interval]: 1.52 [1.11, 2.09]) and ACR70 (1.80 [1.29, 2.51]). In patients who were TNFi-IR, bimekizumab had a significantly greater likelihood of response than risankizumab at Wk52 for ACR20 (1.78 [1.08, 2.96]), ACR50 (3.05 [1.74, 5.32]), ACR70 (3.69 [1.82, 7.46]), and MDA (2.43 [1.37, 4.32]). Conclusions Using MAIC, bimekizumab demonstrated a greater likelihood of efficacy in most ACR and MDA outcomes than risankizumab in patients with PsA who were bDMARD naïve and TNFi-IR at Wk52. Trial Registration NCT03895203, NCT03896581, NCT03675308, NCT03671148.

Abstract Background Tumor necrosis factor inhibitors (TNFi) are frequently chosen as the first biologic for patients with psoriatic arthritis (PsA). Given that many patients with PsA are TNFi inadequate responders (TNF-IR; either inadequate efficacy or intolerance), treatments utilizing alternative mechanisms of action are needed. In phase 3 studies, the fully human interleukin (IL)-23p19 subunit-inhibitor, guselkumab, was efficacious in patients with active PsA, including TNFi-IR. Efficacy was generally consistent between TNFi-naïve and TNFi-experienced cohorts; however, in the latter, higher response rates have been observed with the Q4W dosing regimen relative to the Q8W dosing regimen for some endpoints, suggesting the need to evaluate whether more frequent dosing may provide an incremental clinical benefit for TNFi-IR patients. Methods The phase 3b SOLSTICE study will assess guselkumab efficacy and safety in TNFi-IR PsA patients. Eligibility criteria include a PsA diagnosis for ≥ 6 months; active disease (≥ 3 swollen, ≥ 3 tender joints, C-reactive protein ≥ 0.3 mg/dL); and inadequate efficacy with, and/or intolerance to, one prior TNFi. Participants will be randomized 1:1:1 to guselkumab Q4W or Q8W or placebo→guselkumab Q4W (at Week 24). The primary endpoint is the proportion of patients achieving ≥ 20% improvement in the American College of Rheumatology criteria (ACR20) at Week 24. Major secondary endpoints include ACR50, ACR70; an Investigator’s Global Assessment (IGA) of psoriasis score of 0/1 plus ≥ 2-grade reduction and ≥ 90% improvement in Psoriasis Area and Severity Index (both among patients with ≥ 3% body surface area affected by psoriasis and baseline IGA ≥ 2); minimal/very low disease activity; and changes from baseline in Health Assessment Questionnaire-Disability Index, the 36-item Short-Form Health Survey Physical Component Summary, and Functional Assessment of Chronic Illness Therapy-Fatigue scores. The target sample size (N = 450) is estimated to provide > 90% power in detecting differences between each guselkumab group and the placebo group for the primary endpoint assuming a 2-sided α = 0.05. Cochran-Mantel–Haenszel testing and analyses of covariance will be used to compare efficacy for binary and continuous endpoints, respectively. Discussion Findings from the phase 3b SOLSTICE study, the design of which was informed by results from previously conducted phase 3 studies, is expected to provide important efficacy and safety information on guselkumab therapy in TNFi-IR patients with PsA. Trial registration This trial was registered at ClinicalTrials.gov, NCT04936308, on 23 June 2021.

Objective Evaluate patient‐reported outcomes after 6 months of on‐label guselkumab use in patients with rheumatologist‐diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. Methods This analysis includes registry participants who initiated and persisted with on‐label guselkumab (after US Food and Drug Administration approval for PsA; 100 mg at weeks 0, 4, and every 8 weeks) at their 6‐month follow‐up visit (On‐Label Persisters). Among patients not meeting response criteria at baseline, responses at 6 months were determined for patient‐reported outcomes, including patient‐reported pain (0–100 mm visual analog scale), patient global assessment of arthritis + psoriasis (PtGA; 0–100 visual analog scale), and Health Assessment Questionnaire‐Disability Index (HAQ‐DI; 0‐3). Unadjusted, nominal P values were calculated via single‐proportion, one‐sided test (H0 = 0%; α = 0.05). Results Of 90 On‐Label Persisters, most had treatment‐resistant PsA (92.2% and 73.3% previously received ≥1 and ≥2 biologic/targeted synthetic disease‐modifying antirheumatic drugs, respectively), with mean (SD) baseline patient‐reported pain, PtGA, and HAQ‐DI scores of 57.0 (24.6), 50.3 (24.4), and 0.9 (0.6), respectively. Among those with patient‐reported pain and PtGA scores of at least 15 at baseline, 40.2% (33/82) and 46.8% (36/77), respectively, achieved at least 15‐mm reductions at 6 months; among those with HAQ‐DI scores of at least 0.35 and more than 0.5 at baseline, respectively, 30.4% (21/69) achieved improvements of at least 0.35 and 10.3% (6/58) achieved scores of 0.5 or lower at 6 months (all nominal P

Abstract 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.

Abstract 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

Abstract Introduction Secukinumab is an anti-interleukin (IL)-17A monoclonal antibody indicated for multiple immunological disorders. Here, we aim to summarize secukinumab safety in clinical trials (CTs) and post-marketing setting (PMS) until 25 June 2022. Methods Adverse events (AEs) were summarized with crude reporting rate (RR) per 100 patient-years (PY) in PMS for all reported indications and with exposure-adjusted incident rates (EAIR) per 100 PY in pooled 47 CTs for approved indications. Results Secukinumab exposure totaled 1,159,260 PY in PMS and 27,765 PY in CTs. AEs were mostly (> 80%) non-serious in PMS. EAIR for serious AEs was 7.0/100 PY. Nasopharyngitis (RR 0.59/100 PY, EAIR 16.08/100 PY) and pneumonia (RR 0.14/100 PY, EAIR 0.17/100 PY) were the most common infection and serious infection, respectively. Candida infections (RR 0.20/100 PY, EAIR 2.16/100 PY) were the most common fungal infections. Inflammatory bowel disease (IBD) was observed in PMS (0.14/100 PY) and CTs (0.26/100 PY). Most (76%) patients with prior IBD did not report IBD flare during CTs. PMS monitoring identified paradoxical skin reactions including dyshidrotic eczema (RR 0.006/100 PY) and pyoderma gangrenosum (RR 0.003/100 PY). Conclusion Secukinumab safety profile with increased patient exposure remained favorable. Paradoxical skin reactions were identified in post-marketing monitoring.

Abstract Introduction To evaluate the effect of guselkumab on work productivity and nonwork daily activity impairment and general health status through 2 years in patients who were biologic-naïve with active psoriatic arthritis (PsA) in the phase 3 DISCOVER-2 clinical trial. Methods Adult patients with PsA were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W); at weeks 0, 4, then every 8 weeks (Q8W); or placebo (through week 24 with crossover to guselkumab Q4W). Work productivity and nonwork daily activity impairment were assessed using the Work Productivity and Activity Impairment Questionnaire for PsA (WPAI-PsA) and patient-reported general health status using the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index and EQ-Visual Analog Scale (EQ-VAS). Least-squares (LS) mean changes from baseline in WPAI-PsA domains and EQ-5D-5L/EQ-VAS were assessed through week 100. Changes in employment status were utilized to estimate potential indirect savings from improved work productivity. Results Of 739 randomized patients, 738 had available baseline data for the analyses (Q4W 245; Q8W 248; placebo 245). At week 24, greater improvements in work productivity, nonwork daily activity, and EQ-5D-5L/EQ-VAS were observed in the Q4W and Q8W groups versus the placebo group. At week 100, LS mean reductions in work productivity impairment (− 23.8% to − 28.0%) and nonwork daily activity impairment (– 26.6% to − 29.2%) and improvements in EQ-5D-5L/EQ-VAS (0.14 to 0.15/21.2 to 25.0) were maintained in patients receiving guselkumab. Among patients employed at baseline, 12.1–16.4% were not employed at week 100, and 20.0–25.3% shifted from not employed at baseline to employed at week 100. Potential yearly indirect cost savings (USD) from improved work productivity at week 100 ranged from $16,529 to $19,409. Conclusion Patients with active PsA treated with guselkumab demonstrated reduced impairment in work productivity and nonwork daily activity, together with improvement in general health status and substantial potential cost savings, over a 2-year period. Trial Registration Clinicaltrials.gov identifier: NCT03158285.

Abstract Background To 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. Methods The 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. Results Continuous 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

Abstract Introduction Randomized controlled trials have demonstrated tofacitinib efficacy for psoriatic arthritis (PsA); however, real-world effectiveness data are limited. This real-world analysis assessed baseline demographics/disease characteristics and tofacitinib effectiveness in patients with PsA in the CorEvitas PsA/Spondyloarthritis Registry. Methods This study (NCT05195814) included patients with PsA initiating tofacitinib from December 2017–December 2021, as monotherapy or with oral small molecules (methotrexate/leflunomide/sulfasalazine/apremilast), pre-existing use, or initiated concurrently. Outcomes: mean change from baseline in disease activity/patient-reported outcomes, proportion of patients achieving low disease activity (LDA)/remission at 6 ± 3 months, and discontinuation rates. Results Of 222 patients with PsA who initiated tofacitinib (60.8% as monotherapy), 123 patients had 6 ± 3 months of follow-up. At initiation, 59.7% were female, 92.3% were White, mean age was 56.3 years, PsA duration since diagnosis was 8.2 years, and 25.7% were biologic disease-modifying antirheumatic drug (bDMARD)-naïve. Improvements to 6 ± 3 months were observed with tofacitinib for Clinical Disease Activity Index for PsA (cDAPSA), DAPSA, PsA Disease Activity Score (PASDAS), Clinical Disease Activity Index, body surface area (BSA), tender/swollen joint count, patient fatigue, pain, Patient Global Skin Assessment, and Health Assessment Questionnaire-Disability Index. At 6 ± 3 months, 25.0%/7.8% of patients treated with tofacitinib achieved cDAPSA-defined LDA/remission, 18.2% achieved minimal disease activity, 30.8% had PASDAS ≤ 3.2, 42.9%/29.4% had resolved enthesitis/dactylitis, and 22.5% achieved BSA = 0%. Tofacitinib discontinuation occurred in 51.2% of patients (51.6% of monotherapy initiators) at/prior to 6 ± 3 months (27.6%/23.6%), 57.1% of whom switched to tumor necrosis factor/interleukin-17 inhibitors. Reasons for discontinuation were not reported in 85.3%/79.3% of patients who discontinued at/prior to 6 ± 3 months. Conclusions This real-world US cohort analysis described patients with PsA newly initiating tofacitinib; most were bDMARD-experienced or receiving monotherapy treatment. In patients who remained on therapy (48.8%), tofacitinib was effective across multiple PsA domains at 6 ± 3 months. Limitations included small patient numbers at follow-up and potential selection bias. Trial Registration ClinicalTrials.gov identifier, NCT05195814.

Summary: Infection, autoimmunity, and cancer are principal human health challenges of the 21st century. Often regarded as distinct ends of the immunological spectrum, recent studies hint at potential overlap between these diseases. For example, inflammation can be pathogenic in infection and autoimmunity. T resident memory (TRM) cells can be beneficial in infection and cancer. However, these findings are limited by size and scope; exact immunological factors shared across diseases remain elusive. Here, we integrate large-scale deeply clinically and biologically phenotyped human cohorts of 526 patients with infection, 162 with lupus, and 11,180 with cancer. We identify an NKG2A+ immune bias as associative with protection against disease severity, mortality, and autoimmune/post-acute chronic disease. We reveal that NKG2A+ CD8+ T cells correlate with reduced inflammation and increased humoral immunity and that they resemble TRM cells. Our results suggest NKG2A+ biases as a cross-disease factor of protection, supporting suggestions of immunological overlap between infection, autoimmunity, and cancer.

Abstract Introduction Guselkumab previously showed greater improvements versus placebo in axial symptoms in patients with psoriatic arthritis (PsA) (assessed by Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] and Ankylosing Spondylitis Disease Activity Score [ASDAS]), in post hoc analyses of the phase 3, placebo-controlled, randomized DISCOVER-1 and DISCOVER-2 studies. We now evaluate durability of response in axial-related outcomes through 2 years of DISCOVER-2. Methods DISCOVER-2 biologic-naive adults with active PsA (≥ 5 tender/ ≥ 5 swollen joints, C-reactive protein ≥ 0.6 mg/dl) were randomized to guselkumab 100 mg every 4 weeks (Q4W) or at week 0, week 4, then Q8W, or placebo → guselkumab Q4W at week 24. Among patients with imaging-confirmed sacroiliitis (investigator-identified), axial symptoms were assessed through 2 years utilizing BASDAI, BASDAI Question #2 (spinal pain), modified BASDAI (mBASDAI; excludes Question #3 [peripheral joint pain]), and ASDAS. Mean changes in scores and proportions of patients achieving ≥ 50% improvement in BASDAI (BASDAI 50) and ASDAS responses, including major improvement (decrease ≥ 2.0), were determined through week 100. Treatment failure rules (through week 24) and nonresponder imputation of missing data (post-week 24) were utilized. Mean BASDAI component scores were assessed through week 100 (observed data). Exploratory analyses evaluated efficacy by sex and HLA-B*27 status. Results Among 246 patients with PsA and imaging-confirmed sacroiliitis, guselkumab-treated patients had greater mean improvements in BASDAI, mBASDAI, spinal pain, and ASDAS scores, lower mean BASDAI component scores, and greater response rates in achieving BASDAI 50 and ASDAS major improvement vs. placebo at week 24. Differences from placebo were observed for guselkumab-treated patients in selected endpoints regardless of sex or HLA-B*27 status. At week 100, mean improvements were ~ 3 points for all BASDAI scores and 1.6–1.7 for ASDAS; 49–54% achieved BASDAI 50 and 39% achieved ASDAS major improvement at week 100. Conclusions Guselkumab treatment provided durable and meaningful improvements in axial symptoms and disease activity in substantial proportions of patients with active PsA and imaging-confirmed sacroiliitis. Trial Registration Clinicaltrials.gov NCT03158285.

Abstract Introduction The aim of this work is to evaluate treatment persistence and clinical outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry. Methods Participants with PsA who initiated and persisted with on-label guselkumab use post-Food and Drug Administration (FDA) approval for active PsA (7/13/2020; subcutaneous 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (occurring through 3/31/2023) comprised the primary analysis population (On-Label Persisters). Hierarchical, multiplicity-controlled primary and secondary outcomes were mean (95% confidence interval) changes from baseline at 6 months in clinical Disease Activity Index for PsA (cDAPSA; primary), Physician Global Assessment (PGA) of arthritis and psoriasis (visual analog scale [VAS] 0–100), patient-reported pain (VAS 0–100), and percent body surface area with psoriasis (%BSA). Paired t tests determined changes that were statistically significantly different from 0 (α = 0.05). Results Among 114 patients who initiated on-label guselkumab and had eligible baseline and 6-month visits, 90 (78.9%) had persistent use. Among these On-Label Persisters at baseline, mean duration of PsA symptoms = 13.6 years; mean cDAPSA, PGA, and patient-reported pain = 22.0, 42.3, and 57.0, respectively; 94.4% had a history of psoriasis (mean BSA 7.6%); and 18.9% and 73.3%, respectively, previously received 1 or ≥ 2 biologic/targeted synthetic disease-modifying antirheumatic drugs. The mean change (improvement) in cDAPSA was − 5.4 (− 8.5, − 2.3; p

Abstract Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post hoc analysis assessed tofacitinib efficacy on enthesitis by baseline location and severity, and impact on disease activity and patient-reported outcomes (PROs), in patients with PsA. Methods Data were pooled from two phase 3 studies (NCT01877668/NCT01882439) in patients with PsA receiving tofacitinib 5 or 10 mg twice daily to month (M)6 or placebo to M3. Endpoints were: change from baseline in Leeds Enthesitis Index (LEI) or Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC); proportions of patients with enthesitis, relapsed enthesitis after resolution, de novo enthesitis, low disease activity (LDA) or remission (minimal disease activity/very low disease activity; Psoriatic Arthritis Disease Activity Score; Disease Activity Index for Psoriatic Arthritis, and Composite Psoriatic Disease Activity in Psoriatic Arthritis); and PROs (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] total and arthritis pain Visual Analog Scale scores). Descriptive statistics were generated by visit and treatment. Change from baseline in PROs was evaluated by multivariate linear regression. Results Seven hundred ten patients from two studies were included: 479 had LEI > 0; 545 had SPARCC > 0; and 136 had LEI = 0 and SPARCC = 0 at baseline. At baseline, among patients with LEI > 0 or SPARCC > 0, mean LEI and SPARCC across treatments and enthesitis locations/severities ranged from 1.0–4.4 and 1.3–9.4, respectively. Across several baseline enthesitis locations/severities, changes from baseline in LEI and SPARCC up to M3 were greater with tofacitinib (-2.0–0.4 and -3.5–0.2) vs placebo (-‍0.9–‍0.4 and -1.5–1.1). Enthesitis at M6 was more common in patients with greater baseline enthesitis severity. At M6, ≤ 40% of patients with baseline LEI > 0 or SPARCC > 0 whose enthesitis had resolved by M1/M3 experienced a relapse, and

Objective Real‐world studies assessing treatment response by psoriatic arthritis (PsA) domains are limited. This study aimed to describe the patient characteristics, frequency and combinations of disease domains, disease activity, and patient‐reported outcomes (PROs) by PsA domains in patients who initiated treatment with a tumor necrosis factor inhibitor (TNFi) or interleukin‐17 inhibitor (IL‐17i). Methods Adults with PsA who initiated treatment with a TNFi or an IL‐17i between January 2013 and January 2021 and had a 6 (±3)–month follow‐up were included. The prevalence of PsA domains, the most common domain combinations, treatment persistence, and unadjusted change in disease activity and PROs from baseline to 6 months for each PsA domain were summarized descriptively. Results Of the 1005 eligible patients, 63% were receiving TNFi and 37% were receiving IL‐17i. Forty percent of TNFi and 14% of IL‐17i initiators received these treatments as first‐line therapy. Peripheral arthritis and skin disease were the most common PsA domains identified in 86% and 82% of patients, respectively, and the triad of peripheral arthritis, skin disease, and nail psoriasis was the most common domain combination observed in 14% of patients. More than two thirds (68%) of patients remained on therapy at 6 months’ follow‐up. Improvements in disease activity and PROs were observed across all PsA domains in those receiving TNFi or IL‐17i. Conclusion This real‐world analysis highlights the heterogeneity in domain presentation; therefore, assessing all PsA domains is important for optimal disease management. Improvements in outcomes across all PsA domains demonstrate the effectiveness of TNFi and IL‐17i in diverse patient groups exhibiting different phenotypes of PsA.

Abstract Introduction This study evaluated the efficacy of the interleukin-17A inhibitor secukinumab in patients with oligoarticular psoriatic arthritis (PsA). Methods A total of 84 patients with oligoarticular PsA, defined as 1–4 tender joints and 1–4 swollen joints, were pooled from the FUTURE 2–5 and MAXIMISE trials (NCT01752634, NCT01989468, NCT02294227, NCT02404350, and NCT02721966). Patients were grouped by treatment received at week 12 (secukinumab 300 mg, secukinumab 150 mg, or placebo) and week 52 (any secukinumab 300 mg or any secukinumab 150 mg). Efficacy was assessed by the proportion of patients achieving selected clinical outcomes. The predictors of Disease Activity index for Psoriatic Arthritis (DAPSA) responses at weeks 12 and 52 were identified by logistic regression analysis. Results Secukinumab treatment resulted in greater achievement of DAPSA-based low disease activity (LDA), DAPSA-based remission (REM), DAPSA50, and DAPSA75 than placebo at week 12, with improvements sustained or further increased through week 52. LDA or REM was achieved at week 52 by more than 90% of patients who received either secukinumab dose, although secukinumab 300 mg resulted in the highest achievement of the stringent DAPSA75 and DAPSA REM outcomes. At week 12, younger age was associated with DAPSA LDA or REM and DAPSA50, while lower baseline swollen joint count was associated with DAPSA REM. No predictors were identified at week 52. The safety profile was consistent with the full study populations. Conclusion Secukinumab demonstrated efficacy vs placebo across several outcome measures in patients with oligoarticular PsA at week 12, with sustained or improved responses through week 52.

Abstract Introduction Biologic disease-modifying anti-rheumatic drugs (bDMARDs), including certolizumab pegol (CZP), are effective treatment options for the management of non-radiographic spondyloarthritis (nr-axSpA). In the absence of head-to-head comparisons in nr-axSpA, we conducted a systematic literature review (SLR) and indirect treatment comparison (ITC) to better understand the comparative efficacy of CZP vs. other bDMARDs. Methods Literature searches were conducted in October 2020 in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials in patients with nr-axSpA who had failed at least one non-steroidal anti-inflammatory drug and were treated with bDMARDs. Outcomes of interest included the Assessment of Spondyloarthritis international Society (ASAS), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI) and Disease Activity Index (BASDAI), and spinal pain score. Comparative efficacy was examined using a series of Bucher ITCs in subgroups matched by prior exposure to bDMARDs, disease duration, baseline C-reactive protein (CRP) levels/magnetic resonance imaging (MRI) status, and timepoints, to ensure comparability between studies. Results At 12–16 weeks, treatment with CZP was significantly more likely to achieve ASAS20/40 response and ASDAS-inactive disease status vs. etanercept (ETN), ixekizumab (IXE), and secukinumab (SEC). CZP showed statistically significant improvement in BASDAI, BASFI, and total spine pain score over adalimumab (ADA), ETN, and IXE, and in BASFI over SEC. Among patients with objective signs of inflammation (OSI; elevated CRP levels and/or inflammation on MRI at baseline), CZP had a statistically significant advantage over ETN and SEC (with or without loading dose) in achieving ASAS40, whereas the comparisons with other bDMARDs did not show any statistically significant differences. Conclusion In the overall matched population, CZP performed significantly better than most comparators in improving the clinical outcomes. Among patients with OSI, CZP was found to be superior to SEC (in the MRI−/CRP + and MRI + /CRP− subgroups) and ETN (in the MRI + /CRP− subgroup) and it was comparable to golimumab and IXE across the different OSI subgroups.

Abstract Background Guselkumab, a fully human monoclonal antibody targeting the interleukin (IL)-23p19 subunit, is approved to treat adults with active psoriatic arthritis (PsA). In the Phase 3 DISCOVER-2 trial of 739 bilogico-naïve patients with active PsA, guselkumab 100 mg resulted in less radiographic progression, assessed via change from baseline in PsA-modified van der Heijde-Sharp (vdH-S) score, compared with placebo at week (W) 24 when given at W0, W4, and then every 4 weeks (Q4W) or Q8W. The least squares mean differences from placebo were -0.66 for guselkumab Q4W (p=0.011) and -0.43 for guselkumab Q8W (p=0.072). Reports suggest baseline C-reactive protein (CRP) and joint erosions are strongly prognostic of poor outcomes, especially radiographic progression, in PsA patients. We designed a trial (APEX) to further assess the effect of guselkumab on radiographic progression in patients with active PsA and risk factors for radiographic progression. Methods Patients are eligible for APEX if they have had PsA for ≥6 months and active disease (≥3 swollen and ≥3 tender joints, CRP ≥0.3 mg/dL) despite prior therapy with conventional synthetic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs, with ≥2 joints with erosions on baseline radiographs (hands and feet). The primary and major secondary endpoints are the proportion of patients achieving ≥20% improvement in American College of Rheumatology response criteria (ACR20) response at W24 and change from baseline at W24 in PsA-modified vdH-S score, respectively. Sample sizes of 350/250/350 for guselkumab Q8W/guselkumab Q4W/placebo are expected to provide >99% power to detect significant differences in W24 ACR20 response rates for each guselkumab group vs placebo, as well as ≥90% (Q4W vs placebo) and ≥80% (Q8W vs placebo) power to detect a significant difference in PsA-modified vdH-S score change at W24. A Cochran-Mantel-Haenszel test and analysis of covariance will compare treatment efficacy for the primary and major secondary endpoints, respectively. Discussion DISCOVER-2 findings informed the design of APEX, a Phase 3b study intended to further evaluate the impact of guselkumab in patients with active PsA and known risk factors for radiographic progression. Trial registration This trial was registered at ClinicalTrials.gov, NCT04882098 . Registered on 11 May 2021.

Abstract Background Axial involvement constitutes a specific domain of psoriatic arthritis (PsA). Interleukin (IL)-23 inhibitors have demonstrated improvement in axial PsA (axPsA) symptoms, but have not shown efficacy in treating ankylosing spondylitis (AS), suggesting differences in axPsA processes and treatments. In a post hoc, pooled analysis of patients with investigator- and imaging-confirmed sacroiliitis in two phase 3, randomized, placebo-controlled studies (DISCOVER-1 and DISCOVER-2), patients treated with guselkumab, an IL-23p19 inhibitor, had greater axial symptom improvements compared with placebo. Confirmatory imaging at baseline was restricted to the sacroiliac (SI) joints, occurred prior to/at screening, and was locally read. Methods The STAR study will prospectively assess efficacy outcomes in PsA patients with magnetic resonance imaging (MRI)-confirmed axial inflammation. Eligible, biologic-naïve patients with PsA (N = 405) for ≥ 6 months and active disease (≥ 3 swollen and ≥ 3 tender joints, C-reactive protein [CRP] ≥ 0.3 mg/dL) despite prior non-biologic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs will be randomized (1:1:1) to guselkumab every 4 weeks (Q4W); guselkumab at week (W) 0, W4, then every 8 weeks (Q8W); or placebo with crossover to guselkumab at W24, W28, then Q8W. Patients will have Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4, spinal pain component score (0–10 visual analog scale) ≥ 4, and screening MRI-confirmed axial involvement (positive spine and/or SI joints according to centrally read Spondyloarthritis Research Consortium of Canada [SPARCC] score ≥ 3 in ≥ 1 region). The primary endpoint is mean change from baseline in BASDAI at W24; multiplicity controlled secondary endpoints at W24 include AS Disease Activity Score employing CRP (ASDAS), Disease Activity Index for PsA (DAPSA), Health Assessment Questionnaire – Disability Index (HAQ-DI), Investigator’s Global Assessment of skin disease (IGA), and mean changes from baseline in MRI SI joint SPARCC scores. Centrally read MRIs of spine and SI joints (scored using SPARCC) will be obtained at W0, W24, and W52, with readers blinded to treatment group and timepoint. Treatment group comparisons will be performed using a Cochran-Mantel-Haenszel or chi-square test for binary endpoints and analysis of covariance, mixed model for repeated measures, or constrained longitudinal data analysis for continuous endpoints. Discussion This study will evaluate the ability of guselkumab to reduce both axial symptoms and inflammation in patients with active PsA. Trial registration This trial was registered at ClinicalTrials.gov, NCT04929210 , on 18 June 2021. Protocol version: Version 1.0 dated 14 April 2021.

Abstract Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post-hoc analysis of two phase III studies in patients with PsA treated with tofacitinib assessed dactylitis by location, and the impact on patient-reported outcomes (PROs). Methods Patients received tofacitinib 5 or 10 mg twice daily (BID), or placebo. Endpoints included change from baseline in Dactylitis Severity Score (DSS), proportions of patients with dactylitis, Psoriatic Arthritis Disease Activity Score (PASDAS), and PROs (Health Assessment Questionnaire-Disability Index [HAQ-DI]; Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F]; Short Form-36 Health Survey [SF-36] Physical Component Summary [PCS], Mental Component Summary [MCS], and physical functioning [PF]; arthritis pain; and Work Limitations Questionnaire [WLQ]). Descriptive statistics were generated by visit and treatment. Change from baseline in PROs were evaluated by multivariate linear regression. Results The analysis included 373/337 patients with baseline DSS > 0/DSS = 0. Regardless of location, DSS improvements in patients with DSS > 0 were greater from month 1 with tofacitinib (10 mg BID) versus placebo. For patients with DSS > 0/DSS = 0, both doses of tofacitinib led to mean dactylitis presence ≤ 15%/

Objective Axial disease is common and burdensome in patients with psoriatic arthritis (PsA). Human leukocyte antigen‐B27 (HLA‐B27) is a risk factor for axial PsA; treatment response by HLA‐B27 status is inadequately characterized. This study evaluated responses to biologic disease‐modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) overall and by HLA‐B27 status in patients with PsA axial disease. Methods This observational study included participants in the CorEvitas (formerly Corrona) PsA/Spondyloarthritis Registry who initiated bDMARD or tsDMARD treatment at baseline, had a 6‐month follow‐up visit, fulfilled Classification Criteria for Psoriatic Arthritis, had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4, and had known HLA‐B27 status. Disease characteristics at baseline and 6 months were evaluated overall and by HLA‐B27 status. Association between HLA‐B27 status and treatment response was evaluated using an analysis of covariance model. Results The analysis included 173 bDMARD or tsDMARD treatment initiations (54 [31.2%] among patients with HLA‐B27+ status and 119 [68.8%] among patients with HLA‐B27− status). BASDAI total and component scores decreased by ≤0.84 across groups after 6 months of bDMARD or tsDMARD therapy; these changes are not considered clinically meaningful. HLA‐B27 status was not statistically significantly associated with changes in axial‐related outcomes. Conclusion In patients with PsA axial disease, 6 months of bDMARD or tsDMARD therapy provided only mild improvements in axial‐related outcomes, irrespective of HLA‐B27 status. This continued high disease activity reflects a critical unmet need for focus on the axial domain of PsA and for additional safe and effective therapies for psoriatic axial disease.

Background: Psoriatic arthritis (PsA) impacts the physical health and functional ability of patients, leading to reduced productivity. High unemployment rates and absence due to sickness have been reported in patients with PsA. Objectives: This post hoc study investigated certolizumab pegol treatment impact on workplace and household productivity in patients with PsA, and assessed whether achievement of more stringent disease control was associated with greater improvements in productivity. Design: RAPID-PsA was a 216-week phase III trial. Methods: This post hoc study used a generalised estimating equations (GEE) model to examine the disease activity association, measured using American College of Rheumatology (ACR) and Disease Activity in PSoriatic Arthritis (DAPSA), and workplace and household productivity, assessed using an arthritis-specific Work Productivity Survey (WPS). The GEE model estimated the mean cumulative number of days patients meeting different disease control criteria were affected by absenteeism or presenteeism in the workplace and household. Results: In all, 273 patients were randomised to certolizumab pegol and 183 (67.0%) completed Week 216. At baseline, 60.8% of patients were employed outside the home. Improved disease control, measured using ACR and DAPSA criteria, was associated with fewer cumulative days affected by workplace absenteeism through Week 216: ACR70: 4.1 days, ACR50 to

Abstract Background Understanding the evolving treatment patterns in patients with rheumatoid arthritis (RA) is important for rheumatologists to make the best practice decisions and optimize treatment. Here, we describe treatment patterns among patients newly initiated on biologic and/or nonbiologic RA therapy over time after enrollment in the US Corrona RA registry. Methods This was a retrospective, cohort study of adult patients with RA enrolled in the Corrona RA registry. Patients were included in this study if they initiated therapy with conventional synthetic disease-modifying antirheumatic drug (csDMARD) monotherapy, TNF inhibitor (TNFi) monotherapy, other (non-TNFi) biologic monotherapy, or combination therapy (index therapy); initiated therapy between January 1, 2004, and December 31, 2015 (index date), after enrollment in the Corrona RA registry; had at least 6 months of follow-up time after the index date; and had at least one follow-up visit. Time periods of interest were based on the year of index therapy initiation: 2004–2007, 2008–2011, and 2012–2015. Results This study included 8027 patients. csDMARD monotherapy and TNFi + csDMARD combination therapy were the most common index therapies in the registry (39.9% and 44.9%, respectively, in the 2004–2007 period; 38.6% and 38.2%, respectively, in the 2008–2011 period; and 35.2% for both in the 2012–2015 period). At therapy initiation, a higher proportion of patients who initiated other biologics, whether as monotherapies (54.0%) or in combination with csDMARD (49.9%), had high disease activity than those who initiated csDMARD monotherapy (28.4%). For 2012–2015 vs 2004–2007 and 2008–2011 periods, persistence on a given therapy appeared to decrease for the TNFi monotherapy cohort (48.2% vs 64.3% and 52.4%) and other biologic monotherapy cohort (52.3% vs 71.4% and 54.5%) over 12 months; switching from one therapy to another was common in the Corrona RA registry. Conclusions Increased switching from one therapy to another and decreased time on a given therapy was observed in the Corrona RA registry in the 2012–2015 period. This observation is most likely due to the increased availability of additional treatment options and/or the change in clinical focus, particularly the emphasis on achievement of treat-to-target goals of remission or low disease activity along with more aggressive treatment.

Abstract Background This analysis assessed improvements in patients with radiographic axial spondyloarthritis (r-axSpA) treated with ixekizumab in the Assessment of Spondyloarthritis International Society (ASAS) treatment response domains and additional patient-reported outcomes at 1 year of treatment. Methods COAST-V and COAST-W were 52-week, phase 3, randomized controlled trials evaluating the efficacy and safety of ixekizumab in biologic disease-modifying antirheumatic drug (bDMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced patients with radiographic spondyloarthritis, respectively. Patients were treated with 80-mg ixekizumab either every 2 weeks or every 4 weeks. Patient-reported outcomes included Patient Global Disease Activity, Spinal Pain, stiffness as measured by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Questions 5 and 6, function as measured by the Bath Ankylosing Spondylitis Functional Index, fatigue as measured by the Fatigue Numeric Rating Scale and BASDAI question 1, Spinal Pain at Night, and sleep quality as measured by the Jenkins Sleep Evaluation Questionnaire. Mixed-effects models for repeated measures were used to analyze changes from baseline in patient-reported outcomes from weeks 1 to 16, and descriptive statistics were reported from weeks 20 to 52. Analysis of covariance with Scheffé’s method was used for the ASAS response association analyses. Results This study assessed 341 bDMARD-naïve and 316 TNFi-experienced patients in the placebo-controlled blinded treatment dosing period (weeks 1–16) as well as 329 bDMARD-naïve and 281 TNFi-experienced patients in the dose double-blind extended treatment period (weeks 20–52). bDMARD-naïve or TNFi-experienced patients treated with ixekizumab every 2 weeks and every 4 weeks reported improvements in patient global disease activity, spinal pain, function, stiffness, fatigue, spinal pain at night, and sleep quality through week 52. Greater correlations with improvements in all response domains were seen when comparing ASAS40 responders to ASAS20 non-responders (p

Abstract Background The interleukin-23p19-subunit inhibitor guselkumab effectively treats signs and symptoms of psoriatic arthritis (PsA). We evaluated the effect of guselkumab on fatigue. Methods Across two phase 3 trials of guselkumab (DISCOVER-1, DISCOVER-2), patients with active PsA despite standard therapy were randomized to subcutaneous injections of guselkumab 100 mg every 4 weeks (Q4W, N = 373); guselkumab 100 mg at week 0, week 4, and then Q8W (N = 375); or placebo (N = 372) through week 24, after which patients in the placebo group crossed over to guselkumab Q4W. Fatigue was measured as a secondary endpoint using the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue instrument (range 0–52, higher scores indicate less fatigue). Least-squares mean changes in FACIT-Fatigue scores were compared between treatments using a mixed-effect model for repeated measures. Mediation analysis was used to adjust for indirect effects on fatigue deriving from improvement in other outcomes, including ≥20% improvement in American College of Rheumatology criteria (ACR20; prespecified), minimal disease activity (MDA; post hoc), or C-reactive protein (CRP; post hoc). Results Baseline mean (SD) FACIT-Fatigue scores in DISCOVER-1 (N = 381) and DISCOVER-2 (N = 739), ranging from 29.1 (9.5) to 31.4 (10.1), indicated substantial levels of fatigue relative to the United States general population (43.6 [9.4]). Across studies, mean improvements, and proportions of patients with ≥4-point improvements, in FACIT-Fatigue scores at week 24 with guselkumab Q4W and Q8W (5.6–7.6 and 54–63%, respectively) were larger vs placebo (2.2–3.6 and 35–46%). Improvement in FACIT-Fatigue scores with guselkumab was sustained from week 24 to week 52, with moderate-to-large effect sizes (Cohen’s d = 0.52–0.81 at week 24; 0.66–0.91 at week 52). Mediation analyses demonstrated that substantial proportions of the effects of guselkumab vs placebo on fatigue were direct effect, after adjusting for achievement of ACR20 (Q4W 69–70%, Q8W 12–36% direct effect) or MDA (72–92% across dosing regimens) response or for change in serum CRP concentrations (82–88% across dosing regimens). Conclusions In patients with active PsA, guselkumab 100 mg Q4W or Q8W led to clinically meaningful and sustained improvements in fatigue through 1 year. A substantial portion of the improvement in FACIT-Fatigue scores induced by guselkumab was independent of effects on the achievement of other select outcomes. Trial registration Name of the registry: ClinicalTrials.gov Trial registrations: DISCOVER-1, NCT03162796; DISCOVER-2, NCT03158285 Date of registration: DISCOVER-1, May 22, 2017; DISCOVER-2, May 18, 2017 URLs of the trial registry record: DISCOVER-1, https://clinicaltrials.gov/ct2/show/NCT03162796?term=NCT03162796&draw=1&rank=1 DISCOVER-2, https://clinicaltrials.gov/ct2/show/NCT03158285?term=NCT03158285&draw=2&rank=1

Secukinumab, a selective interleukin (IL)-17A inhibitor, is approved for use in adult and paediatric psoriasis, psoriatic arthritis, ankylosing spondylitis and non-radiographic axial spondyloarthritis. The aim of this study was to report the long-term safety of secukinumab in pooled data from 28 clinical trials and a post-marketing safety surveillance in psoriasis, psoriatic arthritis and ankylosing spondylitis patients. Analyses included 12,637 secukinumab-treated patients, corresponding to 15,063, 5,985 and 3,527 patient-years of exposure in psoriasis, psoriatic arthritis and ankylosing spondylitis patients, respectively. Incidences of serious adverse events were low, with no identifiable patterns across indications. Active tuberculosis or latent tuberculosis infections were rare. The incidence of opportunistic infections was

Abstract Introduction Patients with ankylosing spondylitis (AS) are burdened with symptoms impacting work productivity measured by presenteeism, absenteeism, overall work impairment, and activity impairment. Ixekizumab, a high-affinity monoclonal antibody selectively targeting interleukin-17A, has been demonstrated to improve disease signs and symptoms in two phase 3 trials of AS. This study investigated for 52 weeks the effect of ixekizumab treatment on work productivity in patients with active AS. Methods COAST-V (NCT02696785) and COAST-W (NCT02696798) were phase 3, multicenter, randomized, controlled trials investigating the efficacy of ixekizumab 80 mg every 4 weeks (Q4W) and every 2 weeks (Q2W) in patients with AS naïve to biologic disease-modifying antirheumatic drugs (bDMARDs; COAST-V) or who were inadequate responders or intolerant to tumor necrosis factor inhibitors (TNFi; COAST-W). Work productivity was measured with the Work Productivity and Activity Impairment Questionnaire for Spondyloarthritis at weeks 16 and 52. Absenteeism, presenteeism, and overall work impairment were assessed for patients reporting paid work. Activity impairment was assessed regardless of work status. Results At baseline, 66.2% (434/656) of patients reported paid work. At week 16, bDMARD-naïve patients treated with both ixekizumab dose regimens and TNFi-experienced patients treated with ixekizumab Q2W reported significant improvements in activity impairment (p

Objective Psoriatic arthritis (PsA) requires long‐term treatment, yet safety concerns and monitoring requirements make maintenance a challenge. This analysis of pooled Psoriatic Arthritis Long‐term Assessment of Clinical Efficacy (PALACE) 1, 2, and 3 data describes 3‐year apremilast safety and tolerability in PsA. Methods Patients with active PsA were randomized (1:1:1) to placebo, apremilast 30 mg twice daily, or apremilast 20 mg twice daily. Placebo patients were re‐randomized to apremilast 30 mg twice daily or 20 mg twice daily at week 16 (early escape) or 24. Double‐blind treatment continued to week 52; patients could continue apremilast during an open‐label, long‐term treatment phase. Results In total, 1493 patients received at least one dose of study medication and were included in the safety population (placebo: n = 495; apremilast 30 mg: n = 497; apremilast 20 mg: n = 501). Among patients receiving apremilast, 53.2% (767/1441) completed 3 years of treatment. Greater rates of adverse events (AEs) were reported with apremilast (61.1%; exposure‐adjusted incidence rate [EAIR]/100 patient‐years, 265.1) versus placebo (47.5%; EAIR/100 patient‐years, 200.7) in the placebo‐controlled period. During weeks 0 to ≤52, the most common AEs occurring in apremilast‐exposed patients were diarrhea (13.9%; EAIR/100 patient‐years, 18.6), nausea (12.3%; EAIR/100 patient‐years, 16.0), headache (9.4%; EAIR/100 patient‐years, 12.1), upper respiratory tract infection (9.1%; EAIR/100 patient‐years, 11.5), and nasopharyngitis (6.2%; EAIR/100 patient‐years, 7.7). Most AEs were mild/moderate with apremilast exposure ≤156 weeks. Rates of depression remained low (EAIR/100 patient‐years, 1.8). Major adverse cardiac events (EAIR/100 patient‐years, 0.5), malignancies (EAIR/100 patient‐years, 0.9), and serious opportunistic infections (EAIR/100 patient‐years, 0.0) were infrequent over the 3‐year exposure period. Discontinuation rates due to AEs were low (

Objective To compare the characteristics of patients with axial spondyloarthritis (axSpA) who had enthesitis versus those without enthesitis. Methods This study included adult patients with axSpA enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry (March 2013 to August 2018). Enthesitis was assessed at enrollment via the Spondyloarthritis Research Consortium of Canada Enthesitis Index. Characteristics were compared between patients with and without enthesitis using t tests or Wilcoxon rank‐sum tests for continuous variables and χ2 or Fisher exact tests for categorical variables. Results Of 477 patients with axSpA, 121 (25.4%) had enthesitis (mean, 3.9 sites) at enrollment. Higher proportions of patients with enthesitis were female and had nonradiographic axSpA than those without enthesitis (both P < 0.05). Additionally, higher proportions of patients with enthesitis had prior biologic (38.8% vs 27.2%) and conventional synthetic disease‐modifying antirheumatic drug (csDMARD; 24.8% vs 13.3%) use and were currently receiving a combination of biologics and csDMARDs (28.6% vs 18.1%) than those without enthesitis. Patients with enthesitis had worse disease activity (tender and swollen joint counts, physician global assessment, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondylitis Functional Index), spinal mobility, and quality of life (pain, fatigue, Health Assessment Questionnaire, and EuroQol visual analog scale scores); greater work impairment; and had a history of depression and fibromyalgia than those without enthesitis (all P < 0.05). Conclusion In this US‐based real‐world study, enthesitis in patients with axSpA was associated with worse disease activity and quality of life than those with no enthesitis.

Abstract The Assessment of SpondyloArthritis international Society (ASAS) has defined core sets for (i) symptom-modifying anti-rheumatic drugs (SM-ARD), (ii) clinical record keeping, and (iii) disease-controlling anti-rheumatic therapy (DC-ART). These include the following domains for all three core sets: “physical function,” “pain,” “spinal mobility,” “spinal stiffness,” and “patient’s global assessment” (PGA). The core set for clinical record keeping further includes the domains “peripheral joints/entheses” and “acute phase reactants,” and the core set for DC-ART further includes the domains “fatigue” and “spine radiographs/hip radiographs.” The Outcome Measures in Rheumatology (OMERACT) endorsed the core sets in 1998. Using empirical evidence from axSpA trials, we investigated the efficacy (i.e., net benefit) according to the ASAS/OMERACT core outcome set for axSpA across all interventions tested in trials included in subsequent Cochrane reviews. For all continuous scales, we combined data using the standardized mean difference (SMD) to meta-analyze outcomes involving the same domains. Also, through meta-regression analysis, we examined the effect of the separate SMD measures (independent variables) on the primary endpoint (log [OR], dependent variable) across all trials. Based on 11 eligible Cochrane reviews, from these, 85 articles were screened; we included 43 trials with 63 randomized comparisons. Mean (SD) number of ASAS/OMERACT core outcome domains measured for SM-ARD/physical therapy trials was 4.2 (1.7). Six trials assessed all proposed domains. Mean (SD) for number of core outcome domains for DC-ART trials was 5.8 (1.7). No trials assessed all nine domains. Eight trials (16%) were judged to have inadequate (i.e., high risk of) selective outcome reporting bias. The most responsible core domains for achieving success in meeting the primary objective per trial were pain, OR (95% CI) 5.19 (2.28, 11.77), and PGA, OR (95% CI) 1.87 (1.14, 3.07). In conclusion, selective outcome reporting (and “missing data”) should be reduced by encouraging the use of the endorsed ASAS/OMERACT outcome domains in clinical trials. Overall outcome reporting was good for SM-ARD/physical therapy trials and poor for DC-ART trials. Our findings suggest that both PGA and pain provide a valuable holistic construct for the assessment of improvement beyond more objective measures of spinal inflammation.

Abstract Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). We report the interim safety, tolerability, and efficacy of tofacitinib in PsA patients in OPAL Balance, a 3-year, open-label, long-term extension study (data cut-off: August 2017; database not locked, data may change). Methods Eligible patients from two phase (P) 3 (P3) tofacitinib PsA studies (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) entered OPAL Balance ≤ 3 months after completing the P3 study or discontinuing for reasons other than study-drug-related adverse events (AEs). Patients received open-label tofacitinib 5 mg twice daily (BID), with adjustments to 10 mg BID permitted post-month (M) 1. Certain concomitant conventional synthetic disease-modifying antirheumatic drugs were allowed. Primary endpoints were incidence/severity of AEs and laboratory abnormalities, and changes from baseline in laboratory parameters (reported up to M36 and M30, respectively). Efficacy (clinical/patient-reported outcomes) was reported through M30. Results A total of 686 patients were treated; at data cut-off, 68.2% remained in the study. Mean (range) treatment duration was 641 (1–1032) days; total treatment duration was 1153.2 patient-years. By M36, 79.6, 13.8, and 8.6% of patients reported AEs, serious AEs, and discontinuations due to AEs, respectively. Five deaths occurred; one within the risk period (incidence rate [IR; patients with events/100 patient-years] 0.1). IRs for AEs of special interest were: all (non-serious and serious) herpes zoster, 1.7; serious infections, 0.9; opportunistic infections, 0.3 (all disseminated/multi-dermatomal herpes zoster); malignancies excluding non-melanoma skin cancer (NMSC), 0.8; NMSC, 1.0; major adverse cardiovascular events, 0.3; pulmonary embolisms, 0.1; and arterial thromboembolisms, 0.4. No patients had deep vein thrombosis. Alanine aminotransferase and aspartate aminotransferase levels were elevated ≥ 3-fold the upper limit of normal in 4.0 and 2.2% of patients, respectively. Changes in laboratory parameters were generally stable over time, although lymphocyte counts decreased slightly. Efficacy was maintained through M30. Conclusions In this interim analysis of OPAL Balance, tofacitinib safety and efficacy in patients with PsA appeared to be consistent with those of the P3 studies. Efficacy was maintained over time. Trial Registration ClinicalTrials.gov identifier: NCT01976364.

Abstract Psoriatic arthritis (PsA) is an immune-mediated, clinically heterogeneous disease characterized by arthritis, enthesitis, dactylitis, spondylitis, and psoriasis of the skin and nails. Persistent articular inflammation in patients with PsA can lead to structural damage, which can result in reduced physical function and quality of life. Structural damage can occur rapidly, and irreversible joint damage may be observed if patients are not treated promptly and appropriately. Therefore, evaluating therapeutic agents for their ability to inhibit structural progression has become increasingly important, with radiographic progression becoming a key efficacy outcome in clinical trials in PsA. Here, we review how structural damage and progression are assessed in clinical trials and the use of radiographic progression as a study outcome. We also discuss possible limitations in the current assessment of radiographic progression as well as areas of research that may improve the assessment of structural damage in clinical trials of PsA.

Objective To report the 5‐year efficacy and safety of secukinumab in the treatment of patients with psoriatic arthritis (PsA) in the FUTURE 1 study (NCT01392326). Methods Following the 2‐year core trial, eligible patients receiving subcutaneous secukinumab entered a 3‐year extension phase. Results are presented for key efficacy endpoints for the secukinumab 150‐mg group (n = 236), including patients who escalated from 150 to 300 mg (approved doses) starting at week 156. Safety is reported for all patients (n = 587) who received 1 dose or more of study treatment. Results Overall, 81.8%% (193 of 236) of patients in the secukinumab 150‐mg group completed 5 years of treatment, of which 36.4% (86 of 236) had dose escalation from 150 to 300 mg. Sustained improvements were achieved with secukinumab across all key efficacy endpoints through 5 years. Overall, 71.0%/51.8%/36.3% of patients achieved American College of Rheumatology (ACR) 20/50/70 responses at 5 years. Efficacy improved in patients requiring dose escalation from 150 to 300 mg and was comparable with those who did not require dose escalation. Exposure‐adjusted incidence rates for selected adverse events per 100 patient‐years for any secukinumab dose were serious infections (1.8), Crohn's disease (0.2), Candida infection (0.9), and major adverse cardiac events (0.5). Conclusion Secukinumab provided sustained improvements in the signs and symptoms in the major clinical domains of PsA. Efficacy improved for patients requiring dose escalation from 150 to 300 mg during the study. Secukinumab was well tolerated with no new safety signals.

Abstract Background Enthesitis is one of the psoriatic arthritis (PsA) domains. Patients with enthesitis are associated with worse outcomes than those without enthesitis. The effect of secukinumab on the resolution of enthesitis in patients with PsA was explored using pooled data from the FUTURE 2 and 3 studies. Method Assessments of enthesitis through week 104 used the Leeds Enthesitis Index. These post hoc analyses included resolution of enthesitis count (EC = 0), median time to first resolution of enthesitis (Kaplan-Meϊer estimate), and shift analysis (as observed) of baseline EC (1, 2, or 3–6) to full resolution (FR), stable (similar or reduction of EC), or worse (EC > baseline). Efficacy outcomes (ACR, PASI, HAQ-DI, SF-36 PCS, and DAS28-CRP) were assessed in patients with or without baseline enthesitis. Results are reported for secukinumab 300 and 150 mg in the overall population and by prior TNFi treatment. Results A total of 65% (466/712) of patients had baseline enthesitis. In the overall population, FR was achieved as early as week 16 in 65% (300 mg) and 56% (150 mg) versus 44% (placebo) patients, with further improvements to 91% (300 mg) and 88% (150 mg) at week 104. The majority (89%) of patients without enthesitis at baseline maintained this status at week 104. Median days to resolution of EC were shorter with secukinumab 300 and 150 mg versus placebo (57 and 85 vs 167 days, respectively). In patients with EC of 1 or 2, shift analysis from baseline to week 24 showed that more patients achieved FR with secukinumab 300 mg and 150 mg versus placebo, whereas no difference between secukinumab and placebo was shown in the more severe patients with EC of 3–6. Increases in proportions of patients with FR were observed with secukinumab irrespective of the severity of EC from baseline to week 104. Improvements in efficacy outcomes were similar in patients with or without enthesitis treated with secukinumab 300 mg. Conclusion Secukinumab provided early and sustained resolution of enthesitis in patients with PsA over 2 years. Secukinumab 300 mg provided higher resolution than 150 mg in patients with more severe baseline EC and showed similar overall efficacy in patients with or without enthesitis. Trial registration FUTURE 2: ClinicalTrials.gov, NCT01752634 (date of study registration: December 19, 2012), and EudraCT, 2012-004439-22 (date of study registration: December 12, 2012) FUTURE 3: ClinicalTrials.gov, NCT01989468 (date of study registration: November 21, 2013), and EudraCT, 2013-004002-25 (date of study registration: December 17, 2013)

Abstract Patients with axial spondyloarthritis (axSpA) frequently report pain, stiffness, fatigue, and sleep problems, which may lead to impaired physical activity. The majority of reported-on measures evaluating physical activity and sleep disturbance in axSpA are self-reported questionnaires, which can be impacted by patient recall (reporting bias). One objective measure, polysomnography, has been employed to evaluate sleep in patients with axSpA; however, it is an intrusive measure and cannot be used over the long term. More convenient objective measures are therefore needed to allow for the long-term assessment of both sleep and physical activity in patients’ daily lives. Wearable technology that utilizes actigraphy is increasingly being used for the objective measurement of physical activity and sleep in various therapy areas, as it is unintrusive and suitable for continuous tracking to allow longitudinal assessment. Actigraphy characterizes sleep disruption as restless movement while sleeping, which is particularly useful when studying conditions such as axSpA in which chronic pain and discomfort due to stiffness may be evident. Studies have also shown that actigraphy can effectively assess the impact of disease on physical activity. More research is needed to establish the usefulness of objective monitoring of sleep and physical activity specifically in axSpA patients over time. This review summarizes the current perspectives on physical activity and sleep quality in patients with axSpA, and the possible role of actigraphy in the future to more accurately evaluate the impact of treatment interventions on sleep and physical activity in axSpA. Funding: Novartis Pharmaceuticals Corporation. Plain Language Summary: Plain language summary available for this article.

Abstract Introduction Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) are three common inflammatory rheumatic diseases that can lead to deformities and joint destruction. Few studies have compared disease burden across patients with these diseases. The objective of this study was to compare disease burden in patients with RA, PsA, or axSpA in routine US clinical practice. Methods This study included adults with RA, PsA, or axSpA enrolled in the Corrona RA and PsA/SpA registries between March 2013 and March 2018. Patient and clinical characteristics at enrollment were compared between patients with RA vs. PsA and RA vs. axSpA using t tests or Wilcoxon rank-sum tests for continuous variables and χ 2 or Fisher’s exact tests for categorical variables. Results A total of 11,350 patients with RA, 2003 with PsA, and 495 with axSpA were included. Patients with RA had shorter mean symptom and disease duration (9.4 and 7.6 years, respectively) than those with PsA (11.2 and 8.4 years) or axSpA (16.7 and 9.8 years). Patients with PsA had lower mean physician global assessment (18.6 vs. 27.3), higher patient global assessment (43.2 vs. 36.9), comparable pain (38.9 vs. 39.5), and lower fatigue (41.1 vs. 43.4) scores than those with RA. Patients with axSpA had comparable mean physician global assessment (25.5 vs. 27.3) and higher patient global assessment (50.2 vs. 36.9), pain (46.1 vs. 39.5), and fatigue (48.3 vs. 43.4) scores than those with RA. Conclusions Disease burden in patients with PsA or axSpA was comparable to or greater than that in patients with RA on the basis of common patient-reported outcome measures but appeared lower when assessed using RA disease activity measures, suggesting that disease-specific approaches to care are needed to optimize disease management. Funding This study was sponsored by Corrona, LLC, and financial support was provided by Novartis. The Rapid Service Fee was funded by Novartis. Plain Language Summary Plain language summary available for this article.

Abstract Background The efficacy and safety of apremilast were assessed in patients with psoriatic arthritis (PsA) in three phase III clinical trials with similar designs (PALACE 1, 2, and 3). Methods Following a 24-week, randomized (1:1:1 to apremilast 30 mg twice daily, 20 mg twice daily, or placebo), double-blind phase and a 28-week blinded active treatment phase, patients could receive apremilast in open-label extension studies for an additional 4 years. Eligible adult patients had active PsA for ≥ 6 months and three or more swollen joints and three or more tender joints despite prior treatment with disease-modifying anti-rheumatic drugs. Results A total of 1493 randomized patients received one or more doses of study medication (placebo: n = 496; apremilast 30 mg twice daily: n = 497; apremilast 20 mg twice daily: n = 500). In patients continuing apremilast treatment, response was sustained without new safety issues. At week 260, 67.2% of remaining patients achieved an ACR20 response, and 44.4% and 27.4% achieved ACR50 and ACR70 responses, respectively. Among patients with baseline enthesitis and dactylitis, 62.4% achieved a Maastricht Ankylosing Spondylitis Enthesitis Score of 0 and 80.9% achieved a dactylitis count of 0, respectively. In patients who had ≥ 3% baseline psoriasis body surface area involvement, 43.6% achieved ≥ 75% reduction from the baseline Psoriasis Area and Severity Index scores. The most commonly reported adverse events (AEs) were diarrhea, nausea, headache, upper respiratory tract infection, and nasopharyngitis, with most diarrhea and nausea AEs occurring within the first 2 weeks of treatment and usually resolving within 4 weeks. Reported rates of depression during the study were low (≤ 1.8%). The majority of patients maintained their weight within 5% of baseline during the study. No new safety concerns or increases in the incidence or severity of AEs were observed over the long term. Conclusions Apremilast maintained clinical benefit and a favorable safety profile for up to 5 years among patients with PsA. Trial registration ClinicalTrials.gov NCT01172938, NCT01212757, NCT01212770

Abstract Background To explore the effect of abatacept treatment on patient-reported outcomes (PROs) in psoriatic arthritis (PsA). Methods Patients with PsA were randomised (1:1) to subcutaneous abatacept 125 mg weekly/placebo for 24 weeks with early escape (EE) to open-label abatacept (week 16). Adjusted mean changes from baseline to weeks 16 (all patients) and 24 (non-EE responders) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 (SF-36; physical and mental component summary and domains), Dermatology Life Quality Index and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated. Subpopulations were analysed by baseline C-reactive protein (CRP) level (> vs ≤ upper limit of normal [ULN]) and prior tumour necrosis factor inhibitor (TNFi) exposure. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCIDs) and ≥ normative values (NVs) in HAQ-DI, SF-36 and FACIT-F (week 16 before EE) were analysed. Results In total population, numerically higher improvements in most PROs were reported with abatacept (n = 213) versus placebo (n = 211) at both time points (P > 0.05). Higher proportions of abatacept versus placebo patients reported PRO improvements ≥ MCID and ≥ NV at week 16. At week 16, all PRO improvements were numerically greater (P > 0.05) in patients with baseline CRP > ULN versus CRP ≤ ULN (all significant [95% confidence interval] for abatacept vs placebo); improvements in SF-36 component summaries and FACIT-F were greater in TNFi-naïve versus TNFi-exposed patients (abatacept > placebo). Week 24 subgroup data were difficult to interpret due to low patient numbers. Conclusions Abatacept treatment improved PROs in patients with PsA versus placebo, with better results in elevated baseline CRP and TNFi-naïve subpopulations. Trial registration ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb); date of registration: 23 May 2013.

Abstract Introduction Tumor necrosis factor inhibitors (TNFis) have shown efficacy for the treatment of ankylosing spondylitis (AS). However, many patients may discontinue or switch TNFis due to lack of effect or adverse events. As biologics with alternative mechanisms of action become available for the treatment of AS, it is important to better understand the characteristics of patients who discontinue or have an inadequate response to TNFis to help inform treatment choices regarding initiating or switching to a biologic therapy. This study compared demographic and clinical characteristics of patients with AS who discontinued vs. continued a TNFi by their second follow-up visit in the US-based Corrona Psoriatic Arthritis and Spondyloarthritis (PsA/SpA) Registry. Methods All patients aged ≥ 18 years with AS enrolled in the Corrona PsA/SpA Registry between April 2013 and January 2015 who were receiving or had initiated a TNFi (index therapy) at the time of registry enrollment (baseline) and had ≥ 2 follow-up visits were included. Patient demographics, clinical characteristics, and patient-reported outcome scores at baseline were compared between cohorts of patients who discontinued or continued their TNFi by the second follow-up visit. Results Of the 155 included patients, 37 (23.9%) discontinued their index TNFi therapy by the second follow-up visit (mean follow-up, 17.8 months). Patients who discontinued their TNFi were older (mean age, 52.1 vs. 46.6 years; P = 0.04), were more likely to be obese (59.5% vs. 34.2%; P

Abstract Background Pain is one of the most important domains affecting health-related quality of life (HRQoL) in patients with psoriatic arthritis (PsA). Secukinumab has demonstrated rapid and sustained improvements in signs and symptoms, including HRQoL, among patients with active PsA. This analysis evaluates the effect of secukinumab on patient-reported pain in PsA through 104 weeks of treatment. Methods Pain was assessed through week 104 using clinically relevant measures, including change from baseline in a pain visual analog scale (VAS) and Short Form-36 (SF-36) bodily domain scores; proportion of patients reporting improvements equal to or better than minimum clinically meaningful differences in the pain VAS and SF-36 bodily pain domain scores; and proportion of patients with no, moderate, or extreme pain/discomfort measured by the EuroQoL 5-Dimension 3-Level Questionnaire (EQ-5D-3 L) pain item scores. Correlations of pain measures were analyzed using Pearson’s correlation coefficient. Pre-specified analyses of TNF-naïve patients and patients who stopped TNF-inhibitors (TNFis) due to inadequate responses or safety/tolerability (TNF-IR patients) were performed using “as-observed data.” Results Mean improvements from baseline in pain VAS scores were greater with secukinumab versus placebo by week 3 (− 16.9; P

Abstract Background The study aimed to assess 52-week efficacy and safety of secukinumab self-administration by autoinjector in patients with active psoriatic arthritis (PsA) in the FUTURE 3 study (ClinicalTrials.gov NCT01989468). Methods Patients (≥ 18 years of age; N = 414) with active PsA were randomized 1:1:1 to subcutaneous (s.c.) secukinumab 300 mg, 150 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. Per clinical response, placebo-treated patients were re-randomized to s.c. secukinumab 300 or 150 mg at week 16 (nonresponders) or week 24 (responders) and stratified at randomization by prior anti-tumor necrosis factor (TNF) therapy (anti-TNF-naïve, 68.1%; intolerant/inadequate response (anti-TNF-IR), 31.9%). The primary endpoint was the proportion of patients achieving at least 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24. Autoinjector usability was evaluated by Self-Injection Assessment Questionnaire (SIAQ). Results Overall, 92.1% (300 mg), 91.3% (150 mg), and 93.4% (placebo) of patients completed 24 weeks, and 84.9% (300 mg) and 79.7% (150 mg) completed 52 weeks. In the overall population (combined anti-TNF-naïve and anti-TNF-IR), ACR20 response rate at week 24 was significantly higher in secukinumab groups (300 mg, 48.2% (p < 0.0001); 150 mg, 42% (p < 0.0001); placebo, 16.1%) and was sustained through 52 weeks. SIAQ results showed that more than 93% of patients were satisfied/very satisfied with autoinjector usage. Secukinumab was well tolerated with no new or unexpected safety signals reported. Conclusions Secukinumab provided sustained improvements in signs and symptoms in active PsA patients through 52 weeks. High acceptability of autoinjector was observed. The safety profile was consistent with that reported previously. Trial registration ClinicalTrials.gov NCT01989468. Registered 21 November 2013. EudraCT 2013–004002-25. Registered 17 December 2013.