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INTRODUCTION: In the 330-patient ADVOCATE trial of avacopan for the treatment of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, in which 81% of patients had renal involvement, estimated glomerular filtration rate (eGFR) increased on average 7.3 ml/min per 1.73 m(2) in the avacopan group and 4.1 ml/min per 1.73 m(2) in the prednisone group (P = 0.029) at week 52. This new analysis examines the results in the patient subgroup with severe renal insufficiency at enrollment into the trial, i.e., eGFR ≤20 ml/min per 1.73 m(2). METHODS: eGFR was determined at baseline and over the course of the trial. Changes in eGFR were compared between the 2 treatment groups. RESULTS: In ADVOCATE, 27 of 166 patients (16%) in the avacopan group and 23 of 164 patients (14%) in the prednisone group had a baseline eGFR ≤20 ml/min per 1.73 m(2). At week 52, eGFR increased on average 16.1 and 7.7 ml/min per 1.73 m(2) in the avacopan and prednisone groups, respectively (P = 0.003). The last eGFR value measured during the 52-week treatment period was ≥2-fold higher than baseline in 41% of patients in the avacopan group compared to 13% in the prednisone group (P = 0.030). More patients in the avacopan group versus prednisone group had increases in eGFR above 20, 30, and 45 ml/min per 1.73 m(2), respectively. Serious adverse events occurred in 13 of 27 patients (48%) in the avacopan group and 16 of 23 patients (70%) in the prednisone group. CONCLUSION: Among patients with baseline eGFR ≤20 ml/min per 1.73 m(2) in the ADVOCATE trial, eGFR improved more in the avacopan group than in the prednisone group.

© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ., Objective: To develop and validate updated classification criteria for giant cell arteritis (GCA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate items, (2) prospective collection of candidate items present at the time of diagnosis, (3) expert panel review of cases, (4) data-driven reduction of candidate items, (5) derivation of a points-based risk classification score in a development data set and (6) validation in an independent data set. Results: The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C reactive protein ≥10 mg/L (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging and fluorodeoxyglucose-positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% CI 0.88 to 0.94) with a sensitivity of 87.0% (95% CI 82.0% to 91.0%) and specificity of 94.8% (95% CI 91.0% to 97.4%). Conclusion: The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research.

© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ., Objective: To develop and validate new classification criteria for Takayasu arteritis (TAK). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in six phases: (1) identification of candidate criteria items, (2) collection of candidate items present at diagnosis, (3) expert panel review of cases, (4) data-driven reduction of candidate items, (5) derivation of a points-based classification score in a development data set and (6) validation in an independent data set. Results: The development data set consisted of 316 cases of TAK and 323 comparators. The validation data set consisted of an additional 146 cases of TAK and 127 comparators. Age ≤60 years at diagnosis and imaging evidence of large-vessel vasculitis were absolute requirements to classify a patient as having TAK. The final criteria items and weights were as follows: female sex (+1), angina (+2), limb claudication (+2), arterial bruit (+2), reduced upper extremity pulse (+2), reduced pulse or tenderness of a carotid artery (+2), blood pressure difference between arms of ≥20 mm Hg (+1), number of affected arterial territories (+1 to +3), paired artery involvement (+1) and abdominal aorta plus renal or mesenteric involvement (+3). A patient could be classified as having TAK with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the model area under the curve was 0.97 (95% CI 0.94 to 0.99) with a sensitivity of 93.8% (95% CI 88.6% to 97.1%) and specificity of 99.2% (95% CI 96.7% to 100.0%). Conclusion: The 2022 American College of Rheumatology/EULAR classification criteria for TAK are now validated for use in research.

Peer reviewed: True, Acknowledgements: The RITAZAREM trial is directed by the European Vasculitis Society and the Vasculitis Clinical Research Consortium (VCRC). The primary sponsor is Cambridge University Hospitals NHS Foundation Trust, and there are collaboration and data-sharing agreements with the University of Pennsylvania and the University of Miyazaki and Okayama University in Japan., Funder: Research Committee on Intractable Vasculitides, the Ministry of Health, Labour and Welfare of Japan, OBJECTIVE: Following induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab. METHODS: RITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse). RESULTS: Rituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, p

Objectives ANCA-associated vasculitis (AAV) is a group of multisystem diseases that can have several ocular manifestations. There are published data on ocular manifestations of granulomatosis with polyangiitis (GPA), but few for eosinophilic granulomatosis with polyangiitis (EGPA) or microscopic polyangiitis (MPA). There is little information concerning chronicity, complications, and association with other cranial manifestations of AAV. Methods This study retrospectively analysed longitudinal multicentre cohorts of individuals with AAV followed between 2006 and 2022. Data included diagnosis, demographics, cranial manifestations of disease, presence of manifestations at onset of disease and/or follow-up, and ocular complications of disease. Univariate and multivariable logistic regression analysis assessed associations across disease manifestations. Results Data from 1441 patients were analysed, including 395 with EGPA, 876 with GPA, and 170 with MPA. Ocular manifestations were seen within 23.1% of patients: 39 (9.9%) with EGPA, 287 (32.7%) with GPA, and 12 (7.1%) with MPA at any time in the disease course. There were more ocular manifestations at onset (n = 224) than during follow-up (n = 120). The most common disease-related manifestations were conjunctivitis/episcleritis and scleritis. In multivariable analysis, dacryocystitis, lacrimal duct obstruction, and retro-orbital disease were associated with sinonasal manifestations of GPA; ocular manifestations were associated with hearing loss in MPA. The most common ocular complications and/or damage seen were cataracts (n = 168) and visual impairment (n = 195). Conclusion Ocular manifestations occur in all forms of AAV, especially in GPA. Clinicians should be mindful of the wide spectrum of ocular disease in AAV, caused by active vasculitis, disease-associated damage, and toxicities of therapy.

ObjectiveTo develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA).MethodsPatients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.ResultsThe development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1×109/L (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3–ANCA positivity (−3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1) and haematuria (−1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% CI 77% to 91%) and the specificity was 99% (95% CI 98% to 100%).ConclusionThe 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis demonstrate strong performance characteristics and are validated for use in research.

ObjectiveFollowing induction of remission with rituximab in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) relapse rates are high, especially in patients with history of relapse. Relapses are associated with increased exposure to immunosuppressive medications, the accrual of damage and increased morbidity and mortality. The RITAZAREM trial compared the efficacy of repeat-dose rituximab to daily oral azathioprine for prevention of relapse in patients with relapsing AAV in whom remission was reinduced with rituximab.MethodsRITAZAREM was an international randomised controlled, open-label, superiority trial that recruited 188 patients at the time of an AAV relapse from 29 centres in seven countries between April 2013 and November 2016. All patients received rituximab and glucocorticoids to reinduce remission. Patients achieving remission by 4 months were randomised to receive rituximab intravenously (1000 mg every 4 months, through month 20) (85 patients) or azathioprine (2 mg/kg/day, tapered after month 24) (85 patients) and followed for a minimum of 36 months. The primary outcome was time to disease relapse (either major or minor relapse).ResultsRituximab was superior to azathioprine in preventing relapse: HR 0.41; 95% CI 0.27 to 0.61, pConclusionsFollowing induction of remission with rituximab, fixed-interval, repeat-dose rituximab was superior to azathioprine for preventing disease relapse in patients with AAV with a prior history of relapse.Trial registration numberNCT01697267; ClinicalTrials.gov identifier

Background Tyrosine kinase 2 (TYK2) is an intracellular kinase that mediates the signalling of key cytokines involved in ulcerative colitis (UC) pathophysiology. Deucravacitinib (DEUC) is a novel, oral, selective TYK2 inhibitor that binds to the TYK2 regulatory domain. The safety and efficacy of DEUC were evaluated in patients (pts) with moderately-to-severely active UC. Methods LATTICE-UC (NCT03934216), a randomised, double-blind, placebo (PBO)-controlled, multicentre, Phase 2 trial, enrolled pts with moderately-to-severely active UC (modified Mayo score of 5 to 9 [endoscopic {ES} subscore ≥2, rectal bleeding {RB} subscore ≥1, stool frequency {SF} subscore ≥2) with inadequate response, loss of response, or intolerance to ≥1 conventional or biologic therapy. Pts were randomised 2:1 to oral DEUC 6 mg or PBO twice daily (BID) and stratified by baseline (BL) corticosteroid use and prior exposure to biologics. The primary endpoint was clinical remission (modified Mayo score with subscores of SF ≤1 with ≥1-point decrease from BL, RB=0, and ES ≤1 [modified, excludes friability]) at Week (Wk) 12; endoscopic response (ES ≤1) at Wk 12 was a secondary endpoint. Results Demographic and BL characteristics were generally similar across groups, except for BL disease activity as measured by the modified Mayo score and ES subscore. Most pts (63.4%) were biologic naïve, and 40.5% were receiving concomitant oral corticosteroids (Table 1). Of 131 pts randomised, 104 (79.4%) completed 12 wks of treatment (DEUC, 69/87 [79.3%]; PBO, 35/42 [83.3%]). At Wk 12, clinical remission rates were 14.8% and 16.3% in the DEUC and PBO arms, respectively, in the overall population (P=0.59); 14.0% and 25.9% in biologic-naïve pts; and 16.1% and 0.0% in biologic-experienced pts (Figure 1). At Wk 12, endoscopic response rates were 19.3% and 27.9% in the DEUC and PBO arms, respectively, in the overall population (P=0.88); 15.8% and 37.0% in biologic-naïve pts; and 25.8% and 12.5% in biologic-experienced pts (Figure 2). Pharmacodynamic data suggest insufficient inhibition of TYK2 pathways with DEUC 6 mg BID. Incidence of adverse events (AEs) was 70.1% in the DEUC arm and 47.6% with PBO; rates of serious AEs were 9.2% (n=8) and 4.8% (n=2), respectively. Rash, acne, and worsening of UC were the most common AEs in the DEUC arm. No meaningful changes from BL in mean values of laboratory parameters were observed with DEUC treatment. Conclusion This Phase 2 study of DEUC 6 mg BID in moderately-to-severely active UC did not meet its primary or secondary efficacy endpoints at Wk 12. In biologic-experienced pts, response rates were numerically higher with DEUC compared with PBO. The safety profile was consistent with DEUC trials in psoriasis and psoriatic arthritis.

BackgroundDeucravacitinib (DEUC) is a novel, oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action distinct from Janus kinase (JAK) 1/2/3 inhibitors. DEUC mediates signalling of key cytokines in psoriatic arthritis (PsA) and psoriasis (PsO). DEUC was well tolerated and efficacious vs placebo (PBO) in a Phase 2 trial in patients (pts) with PsA,1 and vs PBO or apremilast in 2 Phase 3 PsO trials.2ObjectivesTo assess the effects of DEUC on multiple laboratory parameters through the first 16 weeks of treatment (PBO-controlled) in these trials.MethodsThe Phase 2 double-blind PsA trial randomised pts (n=203) 1:1:1 to PBO, DEUC 6 mg once daily (QD), or 12 mg QD. The Phase 3 double-blind PsO trials, POETYK PSO-1 and POETYK PSO-2, randomised pts (n=666 and 1020, respectively) 1:2:1 to PBO, DEUC 6 mg QD, or apremilast 30 mg twice daily. Changes from baseline in haematologic (neutrophils, lymphocytes, platelets, haemoglobin) and chemistry (cholesterol, triglycerides, alanine aminotransferase [ALT], aspartate aminotransferase [AST], and creatine phosphokinase [CPK]) parameters were evaluated. Shifts in Common Terminology Criteria for Adverse Events (CTCAE; version 5.0) severity grade ≥3 of laboratory abnormalities were assessed.ResultsIn the PsA trial, 65% of pts were on concomitant conventional synthetic DMARDs (csDMARDs) and 54.7% of pts were on methotrexate. The vast majority of pts continued to have laboratory parameters within normal range throughout the 3 trials in PsO and PsA. No clinically meaningful changes from baseline were observed in laboratory parameters in pts treated with DEUC, PBO, or apremilast. Rates of CTCAE grade 3 and 4 were rare (≤1 pt) and similar across DEUC-, PBO-, and apremilast-treated pts for the following parameters: lymphocytes, neutrophils, platelets, haemoglobin, AST, ALT, and cholesterol (Table 1). Shifts to CTCAE grades ≥3 in triglycerides and CPK were infrequent and generally comparable across treatment arms.Table 1.Maximal shifts to Grades ≥3 in laboratory parameters, Weeks 0-16PsA Phase 2PsO Phase 3aCTCAE TermGradePlacebo (n=66)n (%)DEUC 6 mg QD (n=70)n (%)DEUC 12 mg QD (n=67)n (%)Placebo (n=419)n (%)DEUC 6 mg QD (n=842)n (%)Apremilast 30 mg BID (n=422)n (%)BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16BLWk 1-16Lymphocyte count decreased340000001 (1.4)00000001 (0.2)0001 (0.1)00000Neutrophil count decreased34000000000000001 (0.2)01 (0.1) 01 (0.1)00000Platelet count decreased34000000000000000000000000Anaemia340N/A0N/A0N/A0N/A0N/A0 N/A0N/A0N/A0N/A0 N/A0N/A1 (0.2) N/AAlanine aminotransferase increased34000 000000 0000 0000000000 0Aspartate aminotransferase increased34000000000 01 (1.6)0000 00 01 (0.1)0001 (0.2) 0CPK increased34001 (1.5) 0000 00001 (1.6)1 (0.2) 03 (0.7) 1 (0.2)1 (0.1) 05 (0.6) 6 (0.7)1 (0.2)02 (0.5) 1 (0.2)Cholesterol high3400000000000 00 00 00 00 00000Hypertriglyceridemia34000 01 (1.4) 1 (1.4)2 (2.9) 1 (1.4)1 (1.6) 04 (6.0) 02 (0.5) 1 (0.2)6 (1.5) 04 (0.5)1 (0.1)12 (1.5)2 (0.2)3 (0.7) 08 (2.0) 0aPOETYK PSO-1 and PSO-2 pooled data.BID, twice daily; BL, baseline; CPK, creatine phosphokinase; CTCAE, Common Terminology Criteria for Adverse Events; DEUC, deucravacitinib; N/A, not applicable because there is no haemoglobin value for CTCAE Grade 4 (life-threatening consequences; urgent intervention indicated); PsA, psoriatic arthritis; PsO, psoriasis; QD, once daily; Wk, week.ConclusionDEUC treatment did not result in clinically meaningful laboratory changes, abnormalities often seen with JAK 1/2/3 inhibition, through 16 weeks of treatment in a Phase 2 trial in PsA, despite two-thirds of pts being on concomitant csDMARDs, and in 2 large Phase 3 trials in PsO.References[1]Mease PJ et al. Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase 2 Trial in Psoriatic Arthritis. Ann Rheum Dis. (In Press).[2]Armstrong A et al. Presented at American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Julianne Hatfield, PhD at Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Bristol Myers Squibb.Disclosure of InterestsRoy M. Fleischmann Consultant of: Abbvie, Acea, Akros, Amgen, Bristol Myers Squibb, Celtrion, Eli Lilly & Co., Galvani, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Sandoz, Sanofi Aventis, Taiho, and UCB., Grant/research support from: AbbVie, Acea, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly & Co., Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Pfizer, Roche/Genentech, Samumed, Sanofi Aventis, and UCB, Diamant Thaçi Consultant of: Advisory board, principal investigator, and lecture fees: AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, DS-Pharma, Eli Lilly, Galapagos, Galderma, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Regeneron, Roche-Posay, Samsung, Sandoz-Hexal, Sanofi, and UCB., Melinda Gooderham Consultant of: Investigator, speaker, advisory board member or consultant for: AbbVie, Akros, Amgen, Anaptys Bio, Arcutis, Aslan, Bausch, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Kirin, Leo Pharma, Medimmune, Merck, Novartis, Pfizer, Regeneron, Sanofi Genzyme, SUN Pharma, and UCB., Bruce Strober Consultant of: Honoraria or consultation fees: AbbVie, Almirall, Amgen, Arcutis, Arena, Aristea, Asana, Boehringer Ingelheim, Immunic Therapeutics, Bristol Myers Squibb, Connect Biopharma, Dermavant, Equillium, Janssen, Leo Pharma, Eli Lilly, Maruho, Meiji Seika Pharma, Mindera, Novartis, Pfizer, GlaxoSmithKline, UCB Pharma, Sun Pharma, Ortho Dermatologics, Regeneron, Sanofi-Genzyme, and Ventyxbio; Speaker: AbbVie, Janssen, Lilly, and Sanofi-Genzyme; Scientific co-director (consulting fee): CorEvitas Psoriasis Registry; Investigator: AbbVie, Cara, CorEvitas Psoriasis Registry, Dermavant, Eli Lilly/Dermira, and Novartis., Neil J Korman Consultant of: Advisory board, consulting fees: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Leo Pharma, Novartis, Principia, Regeneron, Sanofi-Genzyme, Sun Pharma, and UCB, Grant/research support from: Grant support/principal investigator: AbbVie, Amgen, Argenx, Bristol Myers Squibb, Celgene, Chemocentryx, Eli Lilly, Galderma, Kyowa Hakko Kirin, Leo Pharma, Menlo, Principia, Prothena, Rhizen, Syntimmune, Trevi, and Xbiotech. Speaker: AbbVie, Eli Lilly, Janssen, Novartis, Regeneron, and Sanofi-Genzyme., Subhashis Banerjee Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Lehman Shareholder of: Employees and shareholders of Bristol Myers Squibb, Employee of: Employees and shareholders of Bristol Myers Squibb, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Antoine Sreih Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Akimichi Morita Consultant of: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio, and UCB Pharma., Grant/research support from: Research grants, consulting fees, and/or speaker’s fees from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Eisai, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi Tanabe, Nichi-Iko, Nippon Kayaku, Novartis, Pfizer, Sun Pharmaceutical Industries, Taiho Pharmaceutical, Torii Pharmaceutical, Ushio, and UCB Pharma., Philip J Mease Consultant of: Consulting and/or speaker fees: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB., Grant/research support from: Research grants: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB

BackgroundPsoriatic arthritis (PsA) is a complex inflammatory disease with manifestations that play an important role in treatment selection.1 Treatments include oral agents, biologic therapies (inhibitors of tumor necrosis factor [TNFi], interleukin [IL-17Ai, IL-12/23i], cytotoxic T lymphocyte–associated antigen 4 inhibitor [CTLA-4i]), and new targeted oral agents (inhibitors of phosphodiesterase-4 [PDE-4i] and Janus kinase [JAKi]).1 Few studies have examined real-world treatment patterns of recently approved therapies.ObjectivesEvaluate real-world treatment patterns for branded systemic therapy in patients with PsA.MethodsIn this retrospective study, medical and pharmacy claims from the US IBM MarketScan Commercial and Medicare databases (1/1/2012–12/31/2019) were used to identify patients with PsA who initiated treatment with a TNFi (adalimumab, etanercept, infliximab, golimumab, or certolizumab), IL-17Ai (secukinumab, ixekizumab), IL-12/23p40i (ustekinumab), IL-23p19i (guselkumab), CTLA-4i (abatacept), JAKi (tofacitinib), or PDE-4i (apremilast). Patients (≥18 years) with ≥1 prescription, ≥2 PsA claims separated by ≥1 day on or before the index date (first prescription date [1/1/13–12/31/2018]), and 1-year continuous enrollment before and after the index date were eligible. Treatment patterns were grouped into continuers, discontinuers, and patients with treatment modification (switchers [without a treatment gap], reinitiators [same drug with a treatment gap], and restarters [different drug with a treatment gap]) (Table 1). Patients were followed for 1 year or until treatment modification, whichever came first. Descriptive statistics were used.Table 1.TerminologyCohortDefinitionn/N (%)ContinuersOn index treatment during 1-year follow-up with no treatment gaps*1910/6455 (29.6)DiscontinuersNo prescription claims for any therapy during 1-year follow-up1614/6455 (25.0)Patients with treatment modificationsAll patients with a change in treatment during 1-year follow-up2908/6455 (45.1)SwitchersPrescription claims for treatments different than index therapy before permissible treatment gaps*794/6455 (12.3)ReinitiatorsPrescription claims for treatments SAME as index therapy AFTER treatment gaps*1686/6455 (26.1)RestartersPrescription claims for DIFFERENT therapy AFTER treatment gap*428/6455 (6.6)Note: All terminology applies to cohorts within the first year of treatment.*Treatment gap: gap of 200% of recommended dosing schedule from end of previous prescription’s days’ supply.ResultsA total of 6455 patients were included (mean age, 50.5 years; 55.5% female; mean Charlson Comorbidity Index score, 0.54). At baseline, the most commonly used therapies were immunosuppressants (58.5%), corticosteroids (52.2%), and nonsteroidal anti-inflammatory drugs (45.9%). Treatments most used at index were TNFi (72.5%; including adalimumab [41.6%] and etanercept [23.8%]) and the PDE-4i apremilast (21.1%). During the 1-year study period, 29.6% of patients maintained their index therapy and 25.0% discontinued. Treatment modification was observed in 45.1% of patients; 12.3% switched to a new therapy without a treatment gap, 26.1% restarted their index therapy, and 6.6% started a new therapy after a treatment gap.ConclusionAmong patients with PsA, there is substantial variability, including high rates of discontinuation within the first year and after index therapy. Further studies are warranted to understand reasons for these treatment patterns.References[1]Ogdie A et al. Treatment guidelines in psoriatic arthritis. Rheumatology (Oxford). 2020;59(Suppl 1):i37-i46.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Statistical analysis support was provided by Arindom Borkakoti, formerly of Mu Sigma. Professional medical writing assistance was provided by LeeAnn Braun, MPH, MEd, of Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Bristol Myers Squibb.Disclosure of InterestsJiyoon Choi Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Antoine Sreih Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Thomas Lehman Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Manasi Suryavanshi Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Qian Xia Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb, Miroslawa Nowak Shareholder of: Bristol Myers Squibb, Employee of: Bristol Myers Squibb

Based on empirical research focused on the phenomenon of corruption in Italy. The purpose of the contribution is to show the different models that are made of corruption pacts according to the actors who regulate them. The basis of the judicial documents was provided by the National Anti-Mafia Directorate (DNAA), the Court of Auditors, and a sample of Courts of Appeal from different jurisdictional districts. The information collected offers an account of the influence that the various mafias have on public policies and the ability to circumvent current legislation. The contribution underlines the existing interpretative limits and why they do not explain to what extent great and small corruption are related.