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Collective negotiation in education has lagged behind collective bargaining developments in private industry, which have resulted from the passage of a number of federal statutes, beginning with the NIRA Act of 1933. By contrast, state statutes for collective negotiation in education have been relatively few, recent, and inadequate. Topics considered include composition of the bargaining unit, compulsory membership, and binding arbitration. Five premises support the NEA position of professional negotiation. Eight premises support the AFT position of collective bargaining. (JK)

BackgroundShared decision making, a cornerstone of RA management1, allows physicians and their patients to make informed decisions about their treatment goals and choice of care. As new treatments become available, it is important to understand rheumatologists’ reasons for choosing JAKi.ObjectivesThis survey evaluated rheumatologists’ clinical and patient centric reasons for choosing JAKi, in addition to exploring alignment between rheumatologists and RA patients in terms of treatment choice and satisfaction.MethodsThe Adelphi RA Disease Specific Programme™2 is a large, multinational, point-in-time survey conducted amongst rheumatologists and their consulting patients with RA in Europe (Belgium, France, Germany, Italy, Spain, UK) between January and October 2020. Physicians completed record forms for up to 10 consecutive RA patients, collecting demographic, clinical and treatment data, and reasons for current treatment choice. Patients were invited to complete a patient questionnaire to assess their satisfaction with ongoing treatment (5-point scale), and perceptions of shared decision making for the current treatment.Results316 rheumatologists provided data for 3121 patients, of whom 1130 (36.2%) completed patient reported questionnaires. Overall, 67% were female, mean age was 53 years (SD 14), 23% had moderate-high disease activity score (DAS28: >3.2). 68% of patients were currently receiving either a biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD; defined here as advanced therapy, AT), 72% were on first line AT. Overall, physicians and their patients were aligned that a conversation took place about a treatment decision (n=855, 79% net alignment), and this was a shared treatment decision (n=814, 75% net alignment). 15% of patients not taking an AT were reported to have a clinical condition warranting one; reasons for not taking AT included patients’ concerns about infection (24%), conventional synthetic DMARDs were tolerable and safe in the patient (18%), and patient dislike of infusions/injections (17%). Of 2143 patients receiving AT, 19% were prescribed JAKi; 57% as monotherapy, 43% as combination therapy. For physician stated reasons for choice of JAKi, factors were driven by both perceptions of clinical efficacy and onset of action, as well as factors relating to patient acceptability such as method of delivery and ease of use (Table 1). With respect to JAKi treatment (n=135 patient-physician pairs), 62% of physicians and their patients were aligned on satisfaction, however 30% of patients reported less satisfaction than their consulting physician (Figure 1).Table 1.Physician stated clinical and patient centric reasons for prescribing a JAKi in their patients with RA (data are percentage of patients; n=397)Reasons for prescribing JAKiPatients (%)Top 5 clinical reasonsStrong overall efficacy74Fast onset of action49Inhibition of disease progression42Strong efficacy as monotherapy39Achievement of clinical remission37Top 5 patient centric reasonsAcceptability of method of delivery for the patient39Enabling patient to perform everyday tasks/activities36Ease of product use (for the patient)33Improvement or maintenance of quality of life30Improving patient’s mood/state of mind14ConclusionCommunicating the choice of pharmacological therapy to patients with RA has become increasingly complex for physicians with expansion of approved treatments. In this subgroup of patients on JAKi, the drug attributes considered as reasons for prescribing were driven by clinical factors as well as by patient centric attributes. Although communications between patients and physicians were largely aligned, better understanding of patient expectations might serve to improve messaging about treatment options and resulting satisfaction.References[1]Smolen JS et al. Ann Rheum Dis 2017;76.[2]Anderson P et al. Curr Med Res Opin 2008;24(11):3063–72.AcknowledgementsThe study was funded by Galapagos NV (Mechelen, Belgium). We thank the physicians and patients who participated in this survey. Medical writing support was provided by Gary Sidgwick, PhD (Adelphi Real World, Bollington, UK) and publications management was provided by Aspire Scientific Ltd, (Bollington, UK), funded by Galapagos NV.Disclosure of InterestsPeter C. Taylor Consultant of: AbbVie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Celgene and Galapagos, Bruno Fautrel Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, Sobi, and UCB, Grant/research support from: AbbVie, Lilly, MSD, and Pfizer, Yves Piette Consultant of: AbbVie, Galapagos, Grünenthal, Novartis, Janssen, and Sandoz, Susana Romero-Yuste Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Grunenthal, Janssen, Kern Pharma, Lilly, Roche, Sandoz, Sanofi, and UCB, Consultant of: AbbVie, Bristol, Biogen, Fresenius, Galapagos, Gebro, Janssen, and Lilly, Grant/research support from: Bristol Myers Squibb, MSD, Novartis, and Pfizer, Jasper Broen Consultant of: Galapagos, Gilead, UCB, and Novartis, Martin Welcker Speakers bureau: AbbVie, Aescu, Amgen, Biogen, BMS, Berlin Chemie, GSK, Hexal, Janssen, Medac, MSD, Mundipharma, Mylan, Novartis, Pfizer, Riemser, Sanofi, and UCB, Consultant of: AbbVie, Boehringer, BMS, Celgene, Galapagos, Gilead, GSK, Medac, Mylan, Novartis, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Actelion, Boehringer, Galapagos, Gilead, GSK, Hexal, Novartis, and UCB, Elizabeth Holdsworth Employee of: Adelphi Real World, Monia Zignani Employee of: Galapagos NV, Katrien Van Beneden Shareholder of: Galapagos NV, Employee of: Galapagos NV, Roberto Caporali Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Galapagos, Gilead, Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, Consultant of: Galapagos, Gilead, Janssen, Lilly, and MSD, Rieke Alten Consultant of: AbbVie, Amgen, Biogen, BMS, Celltrion, Galapagos, Gilead, Janssen, Lilly, Novartis, Pfizer, and Roche

BackgroundPsoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory disease with heterogenous musculoskeletal manifestation (arthritis, spondylitis, enthesitis, dactylitis) and extra-musculoskeletal manifestation (skin and nail psoriasis). In addition, PsA is commonly associated with comorbidities such as metabolic syndrome and cardiovascular diseases where IL-17 is a key driver of this disease.Izokibep is a unique IL-17A inhibitor with extraordinary potency and small molecular size designed to overcome the limitations of monoclonal antibodies such as poor tissue distribution.Here, we report 16-week phase 2 results in patients with active PsA.ObjectivesTo assess efficacy, safety, pharmacokinetics and immunogenicity of izokibep versus placebo.MethodsThis is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-groups, dose-finding trial studying bi-weekly 80 mg or 40 mg izokibep administered subcutaneously versus placebo until Week 16 (Period 1) and dose-controlled treatment until Week 46 (Period 2). PsA patients had to have ≥3 swollen and ≥3 tender joints of the 66/68 joint count, and an inadequate response to previous NSAIDs, csDMARDs or TNF inhibitor therapy. The primary endpoint was to evaluate ACR50 responses of 80 mg bi-weekly versus placebo at Week 16. Key secondary endpoints were ACR20/70, MDA, DAS28, DAPSA, SPARCC, LDI, PASI as well as tolerability and safety. Efficacy outcome measures were assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT04713072.Results135 patients were randomized and treated between June 2020 and July 2021 in 22 European sites located in Austria, Belgium, Czech Republic, Germany, Hungary, Poland and Spain.At baseline, patients had a mean age of 48.5 (SD 12.0) years, a mean BMI of 29.0 (SD 4.8) kg/m2, a mean swollen joint count (SJC) of 9.9 (SD 6.6), and a mean tender joint count (TJC) of 16.7 (SD 10.4). The mean PsA disease duration was 7.1 (SD 7.8) years. 13% failed previous TNF inhibitor treatment and 80% received a concomitant csDMARD.At Week 16, the confirmatory primary endpoint ACR50 response rate was met (p=0.0003). ACR50 response rate was 52% in the 80 mg group, 48% in the 40 mg and 13% in the placebo group. The ACR20/50/70 response rates up to Week 16 by treatment group are presented in Figure 1.Figure 1.ACR20/50/70 response ratesSJC and TJC rapidly decreased with active treatment as indicated in Table 1.Table 1.SJC and TJC by visit until Week 16Mean SJC (SD)Mean TJC (SD)Study WeekPlacebo Q2W N=4440 mg Q2WN=4480 mg Q2WN=47Placebo Q2WN=4440 mg Q2WN=4480 mg Q2WN=47BL9.2 (6.4)10.1 (7.0)10.4 (6.4)16.4 (11.3)16.7 (10.3)17.0 (9.7)28.4 (6.1)7.3 (6.5)7.6 (7.6)14.9 (10.0)13.3 (9.5)13.8 (10.7)47.7 (7.7)6.0 (7.0)5.6 (6.2)14.1 (11.8)12.5 (11.6)11.2 (9.2)86.0 (6.2)3.5 (4.1)3.7 (4.7)10.5 (7.5)9.0 (10.5)7.4 (7.2)125.1 (5.2)2.6 (3.4)2.3 (3.4)10.9 (8.7)8.1 (8.9)6.0 (6.7)165.0 (5.7)2.4 (3.7)1.7 (2.7)10.7 (9.1)7.1 (7.7)5.6 (6.8)There was a dose-response relationship and a fast onset of response.No serious or severe adverse events occurred during Period 1. The three most frequently affected System Organ Classes (SOCs) were SOC General disorders and administration site conditions comprising mainly mild injection site reactions or erythema followed by SOC Infections and infestations and SOC Metabolism and nutrition disorders. One mild, transient vulvovaginal Candida infection with active treatment was reported. Apart from injection site reactions there were no apparent differences in the occurrence of adverse events between active and placebo patients.ConclusionIn this phase 2 study, izokibep showed a dose-dependent high degree of efficacy in patients with active PsA having failed previous treatment. Overall, izokibep was well tolerated.These data strongly support further clinical development.ReferencesNoneAcknowledgementsAffibody AB, Sweden, and ACELYRIN Inc, USA, funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of this publication. All authors participated in the drafting, review, and approval of this publication.Disclosure of InterestsFrank Behrens Shareholder of: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc., Novartis, Speakers bureau: Amgen, Horizon, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion, AbbVie, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc., Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Roche, Alan Kivitz, Peter C. Taylor Consultant of: AbbVie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Celgene and Galapagos, Dieter Wetzel Consultant of: Acino, Affibody, Biotest, Cheplapharm, CSL Behring, Mundipharma, Roche, Sandoz, Temmler, Nikolai C Brun Employee of: Affibody AB, Jan Brandt-Juergens Speakers bureau: Abbvie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac, Gilead, Affibody, Paid instructor for: Abbvie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac, Gilead, Affibody, Edit Drescher: None declared, Eva Dokoupilova: None declared, Anna Rowińska-Osuch: None declared, Nadia Abdel-Kader Martin Speakers bureau: Pfizer in 2011, Kurt de Vlam Speakers bureau: AbbVie, Amgen, Eli Lilly, Novartis, UCB, Paid instructor for: Amgen, Galapagos, UCB, Consultant of: Eli Lilly, Johnson &Johnson, Novartis Galapagos, UCB, Grant/research support from: Celgene

BackgroundPain significantly impacts life of patients with rheumatoid arthritis (RA) (1). Besides articular pain due to systemic inflammation, neuropathic pain (NeP) represents another challenge that can pose a considerable burden on the life of patients (2).ObjectivesTo investigate persisting pain in RA patients and to analyse NeP along with patient-reported outcomes (PROs).MethodsPAIN-CONTROL is a prospective, non-interventional study in rheumatology centres in Germany. Inclusion criteria were fulfilment of the 2010 ACR/EULAR RA classification criteria, disease duration ≤ 8 yrs, DAS28 > 3.2, SJC > 3, CRP normal or above reference range, and pain rating ≥ 50 (0-100 VAS). Eligible subjects had to be scheduled for escalation of anti-inflammatory treatment according to national guidelines. At wk 24 subjects were allocated to three subgroups given DAS28-CRP change and VAS pain: i) reference group: VAS pain < 50 with either DAS28 improvement > 1.2 or DAS28 ≤ 3.2, ii) non-responders: DAS28 improvement ≤ 1.2 and DAS28 > 3.2 with or without pain alleviation, iii) persisting pain: VAS pain ≥ 50 with either DAS28 improvement > 1.2 or DAS28 ≤ 3.2. For groups 1 and 2 end of study was at week 24, patients with persisting pain continued until wk 48. Patients were assessed for NeP using a score of ≥ 19 in the painDETECT questionnaire (PD-Q) (3). Pain-related PROs, i.e. the Rheumatoid Arthritis Impact of Disease Questionnaire (RAID) and the Patient Health Questionnaire (PHQ-9), were analysed along with demographic background information (1,4). Descriptive results are presented as mean (SD) or mean (SD) | Nvalid, as well as n (%) or n (%) | Nvalid, respectively.Results567 subjects were analysed with the following distribution: Reference group 337 (59.4%), non-responders 102 (18.0%), and persisting pain 128 (22.6%), of which 115 patients were available at wk 48. Subgroups showed similar demographic baseline characteristics but differed in PROs (Table 1). Until wk 24, proportion of patients with NeP indication decreased in the reference group (-19.8%) and slightly in non-responders (-6.0%) and persisting pain group (-9.5%). Non-responders showed the highest NeP proportion at wk 24 (35.0%) (Table 1). Of 115 patients with persisting pain at wk 24, 47 (40.9%) tested NeP negative at wk 48, 21 (18.3%) tested unclear, 28 (24.3%) were missing and 19 (16.5%) tested positive. Of the latter 9 patients (47.4%) still had persisting pain at week 48, while this was the case for 14 patients (29.8%) in the former group. 49 (42.6%) of 115 patients with severe persisting pain at wk 24 reported pain alleviation at wk 48 and fulfillment of reference group criteria. RAID and PHQ-9 scores improved in the reference group but only slightly in the other two subgroups.Table 1.Demographic background and PROsCharacteristicReference group(N = 337)Non-responders(N = 102)Persisting pain(N = 128)Gender (f/m)233 (69.1%) /65 (63.7%) /87 (68.0%) /104 (30.9%)37 (36.3%)41 (32.0%)Age57.1 (13.2) | 33759.9 (12.0) | 10257.1 (13.0) | 128Disease duration (yrs)2.5 (2.6) | 3372.7 (2.8) | 1022.5 (2.5) | 128PD-Q (≥ 19) (Bl)82 (28.6%) | 28732 (41.0%) | 7840 (36.0%) | 111PD-Q (≥ 19) (wk 24)21 (8.8%) | 23928 (35.0%) | 8027 (26.5%) | 102PD-Q (Bl)14.0 (6.8) | 28715.5 (7.1) | 7815.5 (6.5) | 111PD-Q (wk 24)8.8 (5.8) | 23914.8 (6.7) | 8013.8 (7.2) | 102RAID (Bl)5.8 (2.0) | 3326.0 (1.9) | 1006.6 (1.7) | 125RAID (wk 24)2.4 (1.8) | 3215.4 (1.9) | 975.1 (1.9) | 123PHQ-9 (Bl)7.3 (5.1) | 3288.4 (5.4) | 987.9 (5.1) | 123PHQ-9 (wk 24)3.8 (3.5) | 3187.3 (4.5) | 956.6 (4.5) | 122ConclusionNeP is common among RA non-responders to anti-inflammatory treatment and in patients with persisting pain, meriting a routine NeP screening to more adequately address persisting pain in these patients. However, even late improvements (after 24 wks) regarding persisting pain seem likely during anti-inflammatory treatment.References[1]Gossec L, Ann Rheum Dis. 2011 Jun;70(6):935–42.[2]Noda K, Mod Rheumatol. 2020 Sep;30(5):828–34.[3]Freynhagen R, Curr Med Res Opin. 2006 Oct;22(10):1911–20.[4]Kroenke K, J Gen Intern Med. 2001 Sep;16(9):606–13.AcknowledgementsStatistical analysis was provided under lead of Dr. Daniela Adolf of StatConsult GmbH, which was funded by AbbVie.Medical writing support was provided by Dr. Matthias Englbrecht of Statscoach, which was funded by AbbVie.Disclosure of InterestsChristoph Baerwald Speakers bureau: Prof. Christoph G. Baerwald has served as consultant to AbbVie and has received research funding and speaker fees from AbbVie., Consultant of: Prof. Christoph G. Baerwald has served as consultant to AbbVie and has received research funding and speaker fees from AbbVie., Grant/research support from: Prof. Christoph G. Baerwald has served as consultant to AbbVie and has received research funding and speaker fees from AbbVie., Edgar Stemmler Shareholder of: Dr. Edgar Stemmler is employee of AbbVie and may own AbbVie stock., Employee of: Dr. Edgar Stemmler is employee of AbbVie and may own AbbVie stock., Sixten Gnuechtel Shareholder of: Dr. Sixten Gnüchtel is employee of AbbVie and may own AbbVie stock., Employee of: Dr. Sixten Gnüchtel is employee of AbbVie and may own AbbVie stock., Katharina Jeromin Shareholder of: Dr. Katharina Jeromin is employee of AbbVie and may own AbbVie stock, Employee of: Dr. Katharina Jeromin is employee of AbbVie and may own AbbVie stock, Carsten Holland Shareholder of: Dr. Carsten Holland is employee of AbbVie and may own AbbVie stock, Employee of: Dr. Carsten Holland is employee of AbbVie and may own AbbVie stock, björn fritz Shareholder of: Dr. Björn Fritz is employee of AbbVie and may own AbbVie stock., Employee of: Dr. Björn Fritz is employee of AbbVie and may own AbbVie stock., Daniela Adolf Consultant of: Dr. Daniela Adolf is an employee of StatConsult GmbH.Statistical analysis was provided under lead of Dr. Daniela Adolf of StatConsult GmbH, which was funded by AbbVie, Peter C. Taylor Speakers bureau: Peter C. Taylor has served as consultant to AbbVie and has received speaker fees from AbbVie, Consultant of: Peter C. Taylor has served as consultant to AbbVie and has received speaker fees from AbbVie, Ralf Baron Speakers bureau: Prof. Ralf Baron has served as consultant to AbbVie and has received speaker fees from AbbVie., Consultant of: Prof. Ralf Baron has served as consultant to AbbVie and has received speaker fees from AbbVie.

BackgroundBaricitinib (BARI), an oral selective Janus kinase 1/2 inhibitor, has demonstrated efficacy in patients (pts) with rheumatoid arthritis (RA) for up to 3 years (yrs) in a long-term extension (LTE) study RA-BEYOND.1ObjectivesDisclose efficacy of BARI in csDMARD-IR pts in the completed LTE study (up to 7 yrs).MethodsIn RA-BUILD, csDMARD-IR pts were randomized 1:1:1 to BARI 4 mg, 2 mg, or placebo (PBO). Completers to week (wk) 24 could enter the LTE and received BARI 4 or 2 mg. In RA-BEAM, MTX-IR pts were randomized 1:1:1 to BARI 4 mg, adalimumab (ADA) 40 mg, or PBO. Completers to wk 52 received BARI 4 mg in the LTE. Pts with no response could be rescued after wk 16 in both studies. Data were analysed by treatment assigned at baseline in originating studies as observed up to time of stepdown (if applicable), study discontinuation or completion, whichever occurred earlier. Efficacy response rates (RR) were assessed as proportions of pts with observed data up to yr 7 (wk 364) for low-disease activity (LDA) (SDAI ≤ 11, DAS28-hsCRP ≤ 3.2, CDAI ≤ 10), remission (REM) (SDAI ≤ 3.3, DAS28-hsCRP < 2.6, CDAI ≤ 2.8, Boolean), and physical function (HAQ-DI ≤ 0.5). No formal statistical comparisons were conducted.ResultsApproximately 56%/25% of pts in BARI 4 mg, 80%/31% in BARI 2 mg, and 60%/25% in PBO from RA-BUILD remained active at yr 3/7; 59%/17% of pts in ADA, 54%/16% in BARI 4 mg, and 67%/14% in PBO from RA-BEAM remained active at year 3/7. SDAI and CDAI had comparable RR for LDA and REM (Table 1). DAS-28CRP LDA RR were similar to SDAI and CDAI, while REM RR were about twice those of SDAI and CDAI (Table 1). HAQ-DI ≤ 0.5 RR was achieved by 25-30% of BARI-treated pts from both trials and maintained to the end of LTE.Table 1.Efficacy outcomes in RA-BEYONDTimeaN/n (%)LDAREMHAQ-DI ≤0.5SDAICDAIDAS-28 CRPSDAICDAIDAS-28 CRPBooleanRA-BEYOND entryBARI 2 mg (BUILD)197/109197/103200/108197/38 (19.3)197/35 (17.8)200/72 (36.0)200/29 (14.5)200/50 (25.0)(55.3)(52.3)(54.0)BARI 4 mg (BUILD)188/113191/116189/112188/33191/35 (18.3)189/75 (39.7)189/26 (13.8)193/44 (22.8)(60.1)(60.7)(59.3)(17.6)BARI 4 mg (BEAM)412/288414/290412/280412/112414/108412/199412/78 (18.9)414/133 (27.3)(69.9)(70.0)(68.0)(27.2)(26.1)(48.3)Yr 3BARI 2 mg (BUILD)156/120158/116156/112156/41 (26.3)158/44 (27.8)156/81 (51.9)156/34 (21.8)159/38 (23.9)(76.9)(73.4)(71.8)BARI 4 mg (BUILD)107/76107/76107/74107/24107/26 (24.3)107/56 (52.3)107/17 (15.9)108/26 (24.1)(71.0)(71.0)(69.2)(22.4)BARI 4 mg (BEAM)222/166224/166222/164222/72224/71 (31.7)222/119222/48224/54 (24.1)(74.8)(74.1)(73.9)(32.4)(53.6)(21.6)Yr 7BARI 2 mg (BUILD)61/5061/4961/5161/17 (27.9)61/18 (29.5)61/40 (65.6)61/12 (19.7)62/16 (25.8)(82.0)(80.3)(83.6)BARI 4 mg (BUILD)45/3748/3745/3445/13 (28.9)48/16 (33.3)45/25 (55.6)45/8 (17.8)48/14 (29.2)(82.2)(77.1)(75.6)BARI 4 mg (BEAM)60/5364/5760/53 (88.3)60/18 (30.0)64/22 (34.4)60/38 (63.3)60/13 (21.7)64/14 (21.9)(88.3)(89.1)N: Number of pts with observed data; n: Number of pts with response. aTime from randomization in originating studies. Entry to RA-BEYOND=wk 24 and wk 52; Yr 3=wk 156 and wk 160; and Yr 7=wk 360 and wk 364 of RA-BUILD and RA-BEAM, respectively.ConclusionIn observed data, BARI demonstrated maintained efficacy in treatment and maintenance of physical function of a csDMARDs-IR RA pt population up to 7 yrs.References[1]Smolen JS, et al. Rheumatology (Oxford). 2021; 60(5):2256-66.Disclosure of InterestsRoberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Eli Lilly and Company, Galapagos, Pfizer, Fresenius-Kabi, MSD, UCB, Roche,Janssen, Novartis, Sandoz, Consultant of: Abbvie, Amgen, BMS, Celltrion, Eli Lilly and Company, Galapagos, Pfizer, MSD, UCB, Janssen, Novartis, Sandoz, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: Abbvie, Amgen, Eli Lilly and Company, Novartis, Roche, SoBi, Sanofi, Raimón Sanmartí Speakers bureau: Eli Lilly and Company, Grant/research support from: Eli Lilly and Company, Tsutomu Takeuchi Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan K.K.; Gilead Sciences, Inc. Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co.; Pfizer Japan Inc.; Sanofi K.K.; UCB Japan Co., Ltd., Consultant of: AbbVie Japan GK, Astellas Pharma, Inc.; Chugai Pharmaceutical Co, Ltd.; Eli Lilly Japan K.K.; Eisai Co., Ltd.; Gilead Sciences, Inc.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Corp., Pfizer Japan Inc., Grant/research support from: AbbVie Japan GK, Asahikasei Pharma Corp., Chugai Pharmaceutical Co, Ltd., DNA Chip Research Inc.; Eisai Co., Ltd., Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Corp., UCB Japan Co., Ltd., Daojun Mo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ewa Haladyj Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Liliana Zaremba-Pechmann: None declared, Peter C. Taylor Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, Roche, and Sanofi, Grant/research support from: Celgene, and Galapagos

BackgroundTraditionally, biologics are maintained lifelong at standard dose in patients with inflammatory arthritis (IA) when sustained low disease activity (LDA) is reached. However, evidence of possible tapering is emerging but data on the optimal approach is lacking.ObjectivesThe primary outcomes at 18 months follow-up are:Superiority: The proportion of patients reduced to ≤50% of their baseline biologic dose.Equivalence: Disease activity (rheumatoid arthritis [RA] and psoriatic arthritis [PsA]: Disease Activity Score28-C-Reactive Protein [DAS28-CRP] and axial spondyloarthritis [axSpA]: Ankylosing Spondylitis Disease Activity Score [ASDAS]).MethodsThe BIODOPT trial was a randomised, open-label, equivalence trial (EudraCT 2017-001970-41). Eligible patients were adults with RA, PsA, or axSpA in LDA on stable biologic doses during ≥12 months. The randomisation ratio was 2:1 (tapering:continuation) stratified by diagnosis, centre, and repeated biologic failures. In the tapering group, the biologic dosing interval was prolonged by 25% every four months until flare or discontinuation. The continuation group was kept on their baseline biologic dosing interval; however, a small increase was allowed (as usual practise) if requested by the patient. The sample size calculation was based on a pre-defined equivalence margin of ±0.5 disease activity points (1.2] or ASDAS [>1.1]) yielding a power of 87% for 180 enrolled patients. All analyses were based on the intention-to-treat population. Continuous outcomes were analysed with repeated-measures linear mixed-effects models with group, diagnosis, centre, repeated biologic failures, time point, and the interaction between group and time as fixed factors and the baseline value of the relevant variable as a covariate. Categorical outcomes were analysed using logistic regression with missing data imputed as trial failures.ResultsBetween May, 2018, and March, 2020, 142 patients were enrolled of which 95 were randomised to tapering and 47 to continuation; inclusion was closed in April 2020 due to national implications of the coronavirus pandemic.At 18 months, significantly more patients in the tapering group (35 patients [(37%]) achieved a significant reduction in their biologic dose (≥50%) compared to the continuation group (one patient [2%]), absolute risk difference (RD) 35%, 95%CI: 24% to 45%, pTable 1.Comparison at 18 months in the ITT populationOutcomeTapering group N = 95Continuation group N = 47Group difference (95%CI)p-valuePrimary outcome:Biologics reduced to ≤50%, n (%)35 (37%)1 (2%)0.35 (0.24 to 0.45)Disease activity, LSMeans (SE)1.84 (0.15)1.75 (0.16)0.08 (-0.12 to 0.29)0.428Key secondary outcomes:Remission1, n (%)63 (66%)33 (70%)-0.04 (-0.20 to 0.12)0.637Low disease activity2, n (%)79 (83%)41 (87%)-0.04 (-0.16 to 0.08)0.511Flares3, n (%)39 (41%)10 (21%)0.20 (0.04 to 0.35)0.011N: number, CI: confidence interval, LSMeans: Least squares means, SE: Standard error.1: RA or PsA: DAS28-CRP 2: RA or PsA: DAS28-CRP 3: RA or PsA: ΔDAS28-CRP >1.2 or ΔDAS28-CRP >0.6 AND current DAS28-CRP ≥3.2. AxSpA: inflammatory back pain AND ΔASDAS ≥0.9 and/or ≥1 swollen joint.ConclusionAcross IA conditions, a significant reduction of biologic dose is possible with disease activity-guided tapering while maintaining a similar disease activity state compared to continuation of biologic as usual care.AcknowledgementsThe authors thank patients, research personnel, and the patient research partners for their contribution to the BIODOPT trial, data manager JHW for technical support and for uploading the concealed allocation sequence, and CCH for data management. The Parker Institute, Bispebjerg and Frederiksberg Hospital is supported by a core grant from the Oak Foundation (OCAY-18-774-OFIL).Disclosure of InterestsLine Uhrenholt Speakers bureau: Abbvie, Eli Lilly, Janssen, and Novartis, Robin Christensen: None declared, Lene Dreyer Speakers bureau: Eli Lilly, Galderma and Janssen, Grant/research support from: BMS (outside the present work), Ellen-Margrethe Hauge Speakers bureau: AbbVie, Sanofi, Sobi, and SynACT Pharma, Grant/research support from: Roche, Novartis, and Novo Nordic Foundation (outside the present work), Annette Schlemmer Speakers bureau: Eli Lilly, Anne Gitte Loft Speakers bureau: AbbVie, MSD, Novartis and UCB, Consultant of: Eli-Lilly, Janssen-Cilag, MSD, Novartis, and UCB, Mads Nyhuus Bendix Rasch Speakers bureau: Sobi, Hans Christian Horn: None declared, Katrine Gade: None declared, Peter C. Taylor Consultant of: AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, Roche, and Sanofi, Grant/research support from: Celgene, and Galapagos (outside the present work), Salome Kristensen: None declared.

Background: Ischemic heart disease is the main cause of death globally. Cardioprotection is the process whereby mechanisms that reduce myocardial damage, and activate protective factors, contribute to the preservation of the heart. Targeting these processes could be a new strategy in the treatment of post-ischemic heart failure (HF). Triiodothyronine (T3) and thyroxine (T4), which have multiple effects on the heart, prevent myocardial damage. Results: This study describes the formulation, and characterization, of chemically modified polymeric nanoparticles incorporating T3, to target the thyroid hormone receptors. Modified T3 was conjugated to polylactide-co-glycolide (PLGA) to facilitate the active targeting of PLGA-T3. Modified T3 and PLGA-T3 was characterized with 1H-NMR. Protective role of synthesized Phosphocreatine (PCr) encapsulated PLGA-T3 nanoparticles (PLGA-T3/PCr NPs) and PLGA-T3 nanoparticles (PLGA-T3 NPs) in hypoxia-mediated cardiac cell insults were investigated. Conclusions: Data demonstrated that PLGA-T3/PCr NPs represent a potentially new therapeutic for the control of tissue damage in cardiac ischemia and resuscitation.

BackgroundBaricitinib (BARI), an oral selective Janus kinase 1/2 inhibitor, is approved for treatment of adults with moderately-to-severely active rheumatoid arthritis (RA). BARI demonstrated efficacy in patients (pts) with RA who have inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) in a 24-week (wk) phase 3 study, RA-BEACON.1 BARI efficacy was evaluated up to 3 years (yrs) of treatment in a long-term extension (LTE) study, RA-BEYOND.2ObjectivesDisclose long-term efficacy of BARI 4 mg and 2 mg in bDMARD-IR pts in the completed study RA-BEYOND.MethodsIn RA-BEACON, pts were randomized 1:1:1 to BARI 4 mg, 2 mg, or PBO; pts with no response could be rescued after wk 16. Completers to wk 24 could enter with BARI 4 or 2mg RA-BEYOND for up to 360 wks (6.9 yrs). LTE data were analysed by treatment assigned at baseline in RA-BEACON as observed up to time of stepdown (if applicable), study discontinuation, or study completion, whichever occurred earlier. Efficacy response rates (RR) were assessed as proportions of pts with observed data up to wk 360 for low-disease activity (LDA) (SDAI ≤ 11, DAS28-hsCRP ≤ 3.2, CDAI ≤ 10), remission (REM) (SDAI ≤ 3.3, DAS28-hsCRP < 2.6, CDAI ≤ 2.8, Boolean), and physical functioning (HAQ-DI ≤ 0.5). No formal statistical comparisons were conducted.Results156, 152, and 140 pts entered the LTE (4 mg, 2 mg, and PBO, respectively). Pts in BARI 4 and 2 mg arms had higher LDA and REM RR vs PBO at LTE entry (wk 24) (Table 1). PBO-treated pts achieved comparable RR to pts in the BARI 4 mg arm by wk 48 (24 wks after switch to BARI 4 mg) and up to wk 360. Of pts enrolled to RA-BEYOND, approx. 50% in BARI 4 mg, 65% in 2 mg and 61% in PBO remained active at wk 156; 17%, 26% and 26% at wk 360, respectively. SDAI LDA RR were 47%/70% and 61%/74% for pts treated with BARI 4 mg and 2 mg, at wk 156 (yr 3)/ 360 (yr 6.9), respectively; SDAI REM RR were 15%/26% and 26%/26% for BARI 4 mg and 2 mg, at wk 156/360, respectively (Table 1). SDAI and CDAI had comparable RR. DAS-28CRP LDA RR were similar to SDAI and CDAI, while REM RR were about twice those of SDAI and CDAI. HAQ-DI ≤ 0.5 RR was 15%/26% (BARI 4 mg), 21%/15% (BARI 2mg), and 9%/3% (PBO) at 3/6.9 yrs.Table 1.Efficacy outcomes in RA-BEYONDTimeaN/n (%)LDAREMSDAICDAIDAS-28 CRPSDAICDAIDAS-28 CRPBooleanHAQ-DI ≤0.5Wk 24PBOb135/31 (23.0)138/32 (23.2)135/31 (23.0)135/6 (4.4)138/8 (5.8)135/14 (10.4)135/3139/6 (4.3)(2.2)BARI 2 mg148/42 (28.4)152/43 (28.3)148/38 (25.7)148/10 (6.8)152/10 (6.6)148/22 (14.9)148/9152/17 (11.2)(6.1)BARI 4 mg150/57 (38.0)156/60 (38.5)150/60 (40.0)150/14 (9.3)156/17 (10.9)150/37 (24.7)150/11 (7.3)156/17 (10.9)Wk 48PBO128/59 (46.1)129/58 (45.0)128/58 (45.3)128/14 (10.9)129/15 (11.6)128/31 (24.2)128/5130/6 (4.6)(3.9)BARI 2 mg139/54 (38.8)140/56 (40.0)139/53 (38.1)139/13 (9.4)140/14 (10.0)139/30 (21.6)139/11 (7.9)140/16 (11.4)BARI 4 mg147/70 (47.6)149/71 (47.7)147/68 (46.3)147/22 (15.0)149/19 (12.8)147/49 (33.3)147/14 (9.5)149/19 (12.8)Wk 156PBO84/47 (56.0)85/47 (55.3)84/45 (53.6)84/15 (17.9)85/14 (16.5)84/33 (39.3)84/985/8 (9.4)(10.7)BARI 2 mg98/60 (61.2)99/60 (60.6)98/58 (59.2)98/25 (25.5)99/27 (27.3)98/43 (43.9)98/13 (13.3)99/21 (21.2)BARI 4 mg76/36 (47.4)78/35 (44.9)76/37 (48.7)76/11 (14.5)78/13 (16.7)76/25 (32.9)76/978/12 (15.4)(11.8)Wk 360PBO33/26 (78.8)35/25 (71.4)34/27 (79.4)33/8 (24.2)35/9 (25.7)34/17 (50.0)34/636/1 (2.8)(17.6)BARI 2 mg38/28 (73.7)38/28 (73.7)38/27 (71.1)38/10 (26.3)38/8 (21.1)38/20 (52.6)38/539/6 (15.4)(13.2)BARI 4 mg27/19 (70.4)27/20 (74.1)27/20 (74.1)27/7 (25.9)27/7 (25.9)27/15 (55.6)27/427/7 (25.9)(14.8)N: Number of pts with observed data; n: Number of pts with response. aNumber of wks from randomisation. bTreatment groups as assigned at randomisation.ConclusionIn observed data, BARI maintained efficacy and normative physical function bDMARD-IR population up to 6.9 yrs (360 wks).References[1]Genovese MC et al. N Engl J Med. 2016; 374:1243-52[2]Wells AF et al. Rheumatol Ther. 2021; 8:987–1001Disclosure of InterestsRoberto Caporali Speakers bureau: Abbvie, Amgen, BMS, Celltrion, Eli Lilly and Company, Galapagos, Pfizer, Fresenius-Kabi, MSD, UCB, Roche,Janssen, Novartis, Sandoz, Consultant of: Abbvie, Amgen, BMS, Celltrion, Eli Lilly and Company, Galapagos, Pfizer, MSD, UCB, Janssen, Novartis, Sandoz, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Eli Lilly and Company, Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: Abbvie, Amgen, Eli Lilly and Company, Novartis, Roche, SoBi, Sanofi, Raimón Sanmartí Speakers bureau: Eli Lilly and Company, Grant/research support from: Eli Lilly and Company, Tsutomu Takeuchi Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan K.K.; Gilead Sciences, Inc. Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Co.; Novartis Pharma Co.; Pfizer Japan Inc.; Sanofi K.K.; UCB Japan Co., Ltd., Consultant of: AbbVie Japan GK, Astellas Pharma, Inc.; Chugai Pharmaceutical Co, Ltd.; Eli Lilly Japan K.K.; Eisai Co., Ltd.; Gilead Sciences, Inc.; Janssen Pharmaceutical K.K.; Mitsubishi-Tanabe Pharma Corp., Pfizer Japan Inc., Grant/research support from: AbbVie Japan GK, Asahikasei Pharma Corp., Chugai Pharmaceutical Co, Ltd., DNA Chip Research Inc.; Eisai Co., Ltd., Eli Lilly Japan K.K.; Mitsubishi-Tanabe Pharma Corp., UCB Japan Co., Ltd., Daojun Mo Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ewa Haladyj Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Liliana Zaremba-Pechmann: None declared, Peter C. Taylor Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, Roche, and Sanofi, Grant/research support from: Celgene and Galapagos

BackgroundFatigue is a prevalent symptom of ankylosing spondylitis (AS)1 and can contribute to higher levels of disease, disability and poor health-related quality of life.2 Back pain and morning stiffness are also commonly reported symptoms.3 Tofacitinib is an oral Janus kinase inhibitor for the treatment of adult patients (pts) with AS. In randomised studies, pts with active AS treated with tofacitinib experienced greater improvements in fatigue, back pain and morning stiffness at Week 12 and 16 of treatment compared with placebo (PBO).4,5 Treatment of these symptoms is a priority for pts with AS and their healthcare providers, however, the mechanisms underlying the interrelationships between fatigue, back pain, morning stiffness and treatment are unclear.ObjectivesTo describe the interrelationships between fatigue, back pain, morning stiffness and tofacitinib treatment in pts with AS, using mediation modelling.MethodsData from Phase 2 (NCT01786668)4 and Phase 3 (NCT03502616)5 studies of pts with active AS treated with tofacitinib 5 mg twice daily (BID) or PBO were used. Mediation modelling, a statistical method to assess the extent to which the effect of an independent variable on a dependent variable is indirect, via identified mediators, or direct, capturing all other (unmeasured) effects, was applied.6,7 The initial model included: treatment as the independent binary variable (tofacitinib 5 mg BID vs PBO); fatigue (measured by Functional Assessment of Chronic Illness Therapy-Fatigue) as the dependent variable; mediators included back pain (measured by total back pain/nocturnal spinal pain [numerical rating scale, 0–10]) and morning stiffness (represented by the mean of Bath Ankylosing Spondylitis Disease Activity Index questions 5 and 6).ResultsPooled data from 370 pts were included in the analysis. The initial model showed that 57.5% (pConclusionOverall, indirect pathways via morning stiffness accounted for ~84% of the effect of tofacitinib treatment on fatigue: (1) treatment affects morning stiffness, which impacts fatigue; and (2) treatment affects morning stiffness, which affects back pain and, ultimately, back pain affects fatigue. The indirect pathway via back pain alone accounted for ~16% of treatment effect on fatigue. These results suggest that in tofacitinib-treated pts with AS, improvements in fatigue are fully mediated through combined treatment effects on morning stiffness and back pain.References[1]Schneeberger EE et al. Clin Rheumatol 2015; 34: 497-501.[2]Connolly D et al. Occup Ther Int 2019; 2019: 3027280.[3]Braun J. Rheumatology (Oxford) 2018; 57: vi1-vi3.[4]van der Heijde D et al. Ann Rheum Dis 2017; 76: 1340-1347.[5]Deodhar A et al. Ann Rheum Dis 2021; 80: 1004-1013.[6]Richiardi L et al. Int J Epidemiol 2013; 42: 1511-1519.[7]Cappelleri JC et al. Boca Raton, FL: CRC Press, 2013.AcknowledgementsStudy sponsored by Pfizer Inc. Medical writing support was provided by Robyn Wilson, CMC Connect, and funded by Pfizer Inc.Disclosure of InterestsLars Erik Kristensen Speakers bureau: AbbVie, Biogen, Eli Lilly, Galapagos NV, Gilead Sciences, Janssen, Pfizer Inc, Sanofi, UCB, Consultant of: AbbVie, Biogen, Eli Lilly, Galapagos NV, Gilead Sciences, Janssen, Pfizer Inc, Sanofi, UCB, Grant/research support from: AbbVie, Eli Lilly, Pfizer Inc, UCB, Peter C. Taylor Consultant of: AbbVie, BMS, Biogen, Celltrion, Eli Lilly, Fresenius, Galapagos NV, Gilead Sciences, GSK, Janssen, Nordic Pharma, Pfizer Inc, Sanofi, UCB, Grant/research support from: Celgene, Galapagos, Victoria Navarro-Compán Speakers bureau: AbbVie, Janssen, Lilly, MSD, Pfizer Inc, UCB, Consultant of: AbbVie, Janssen, Lilly, Moonlake, MSD, Pfizer Inc, UCB, Grant/research support from: AbbVie, Novartis, Marina Magrey Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Grant/research support from: AbbVie, UCB, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Arne Yndestad Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Oluwaseyi Dina Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

BackgroundResidual pain often remains in patients (pts) with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) who achieve low disease activity or remission.1,2 Tofacitinib is an oral JAK inhibitor for the treatment of RA and PsA. A descriptive analysis showed that tofacitinib may have a beneficial effect on residual pain in pts with PsA with abrogated inflammation.3ObjectivesTo assess efficacy of tofacitinib, adalimumab (ADA) and placebo (PBO) on residual pain in pts with RA and PsA with abrogated inflammation, using a network meta-analysis (NMA).MethodsData were pooled from 9 randomised clinical trials of pts with RA (NCT00960440/NCT00847613/NCT00814307/NCT00856544/NCT00853385/NCT01039688/NCT02187055) or PsA (NCT01877668/NCT01882439). This analysis included pts who received ≥1 dose of tofacitinib 5 mg twice daily (BID), ADA 40 mg once every 2 weeks or PBO with background therapy, and had abrogated inflammation (swollen joint count [SJC] = 0 and C-reactive protein [CRP] NCT00853385/NCT02187055/NCT01877668; NCT02187055 performed tofacitinib/ADA non-inferiority/superiority comparisons. Primary outcome was pt assessment of Pain (visual analogue scale [VAS] 0 [no pain] – 100 mm [most severe pain]) at M3; scores were summarised descriptively; treatment comparisons were assessed by Bayesian NMA on individual pt-level data, accounting for within-trial imbalances and treatment effect modifiers.ResultsAbrogated inflammation at M3 was achieved in 14.1% (328/2330), 14.9% (87/585) and 3.0% (20/673) of RA and 22.7% (54/238), 29.2% (31/106) and 12.7% (30/236) of PsA pts receiving tofacitinib, ADA and PBO, respectively. RA and PsA pts receiving tofacitinib/ADA had higher CRP vs pts receiving PBO. RA pts receiving tofacitinib/ADA had lower SJC and longer disease duration vs pts receiving PBO. PsA pts receiving tofacitinib had a longer disease duration and higher Pain VAS vs pts receiving ADA/PBO. In both groups, a lower % of female pts received tofacitinib/ADA vs PBO (Table 1). Observed median (Q1; Q3) values for Pain VAS at M3 were 17.0 (6.0; 31.0), 19.0 (7.0; 31.0) and 33.5 (7.0; 48.0) in RA and 24.0 (8.0; 44.0), 21.0 (9.0; 49.0) and 27.0 (8.0; 52.0) in PsA pts treated with tofacitinib, ADA or PBO, respectively. Differences between active treatments and PBO were less prominent in PsA vs RA pts, per posterior probability values (Fig).Table 1.Demographics and baseline characteristics of pts with abrogated inflammation at M3RAPSATofacitinib 5 mg BID (N=328)ADAa 40 mg Q2W (N=87)PBO(N=20)Tofacitinib 5 mg BID (N=54)ADAa 40 mg Q2W (N=31)PBO(N=30)Age, yrs, mean (SD)50.7(12.8)49.2(13.9)44.6(9.9)51.1(11.7)47.4(11.6)49.7(11.6)Female, %79.077.090.044.435.570.0Weight, kg, mean (SD)68.9(16.9)72.5(21.8)71.4(25.0)89.1(22.7)83.2(19.0)76.7(15.7)Disease duration, yrs, median (Q1; Q3)4.8(1.4; 9.5)5.8(2.4; 11.1)2.6(1.7; 8.5)7.8(4.0; 14.3)2.7(1.0; 6.0)4.3(2.7; 10.0)SJC, median(Q1; Q3)9.0(7.0; 14.0)8.0(6.0; 12.0)10.5(9.0; 19.5)6.0(4.0; 10.0)5.0(4.0; 8.0)5.0(4.0; 7.0)CRP, mg/L, median (Q1; Q3)8.0(3.6; 20.0)8.6(3.6; 15.7)3.9(1.4; 6.4)3.7(1.1; 9.2)3.6(1.2; 12.5)2.2(1.2; 4.5)Pain VAS, median (Q1; Q3)57.0(39.0; 72.7)52.5(35.0; 69.0)62.0(38.5; 67.0)58.0(51.0; 75.0)48.0(36.0; 65.0)48.5(21.0; 61.0)aADA was included in NCT00853385/NCT02187055/NCT01877668; NCT02187055 performed tofacitinib/ADA non-inferiority/superiority comparisons.N, number of pts; Q1, 1st quartile (25th percentile); Q2W, once every 2 weeks; Q3, 3rd quartile (75th percentile); SD, standard deviation.ConclusionIn this NMA, pts with RA and PsA achieving abrogated inflammation with tofacitinib or ADA at M3 had greater residual pain reduction vs those receiving PBO. This may imply that tofacitinib/ADA have analgesic benefits beyond those related to inflammation reduction.References[1]Michaud et al. Arthritis Care Res 2021; 73: 1606-1616.[2]Kilic et al. Rheumatol Int 2019; 39: 73-81.[3]Dougados et al. Arthritis Rheumatol 2019; 71 (S10): Abs 1502.AcknowledgementsStudy sponsored by Pfizer Inc. Medical writing support was provided by Lewis Rodgers, CMC Connect, and funded by Pfizer Inc.Disclosure of InterestsMaxime Dougados Consultant of: AbbVie, Eli Lilly, Gilead Sciences, Janssen, Merck, Novartis, Pfizer Inc and UCB, Grant/research support from: AbbVie, Eli Lilly, Gilead Sciences, Janssen, Merck, Novartis, Pfizer Inc and UCB, Peter C. Taylor Consultant of: AbbVie, Biogen, Bristol-Myers Squibb, Celltrion, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, Roche, Sanofi and UCB, Grant/research support from: Celgene and Galapagos, Clifton Bingham Consultant of: AbbVie, Bristol-Myers Squibb, Gilead Sciences, Eli Lilly, Janssen, Pfizer Inc and Sanofi/Genzyme, Grant/research support from: Bristol-Myers Squibb, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Yves Brault Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Satrajit Roychoudhury Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Meriem Kessouri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

BackgroundTNF-α inhibitor therapy has long been the standard of care for adult patients diagnosed with moderate to severe rheumatoid arthritis (RA) across the EU5, though several new biologics, biosimilars, and small molecules have become available for the treatment of RA.ObjectivesThis research sought to understand the factors influencing treatment changes when patients are switched from one biologic or small molecule to another, including the reason(s) for their treatment selection.MethodsAn independent market analytics firm collaborated with EU5 rheumatologists (n=250 across France, Germany, Italy, Spain, and the UK) to conduct a retrospective chart review of patients diagnosed with RA (n=1,268) who had switched from one biologic therapy or small molecule agent to another in the prior twelve weeks. Data were collected in August and September 2021 and included clinical and non-clinical patient demographics as well as physician demographics and attitudinal survey responses. This study was a non-longitudinal trending analysis to 2020 (n=1,288), 2019 (n=1,294), 2018 (n=1,312) and 2017 (n=1,235) audits following the same methodology.Results70% of surveyed rheumatologists reported recent changes to the management of their RA patients, with the most recalled treatment shift being an increased use of small molecule agents (JAK inhibitors, 30%), attributable to the introduction of upadacitinib and filgotinib in December 2019 and September 2020, respectively. Despite a plethora of RA treatment options in the EU5, annual physician-reported rates of RA patient switching have remained stable since 2017, with 25% of biologic/small molecule-treated patients switching brands within a given year.There has been a steady increase in switches from TNF inhibitors to JAK inhibitors over the last few years (2% in 2017 to 19% in 2021). At the same time, the rates of TNF cycling have been on a downward trend (43% in 2017, 40% in 2018, 39% in 2019, 34% in 2020, and 32% in 2021). Rheumatologists indicate 44% of their RA switch patients were switched from a TNF to a JAK inhibitor due to secondary efficacy failure, and their primary reason for selecting a JAK was due to the specific MOA (40%) and dosing delivery (19%).TNF cycling (both branded and biosimilar) represent one-third of all switches in the EU, making it the most common switch pattern. TNF cycling remains most common in Germany and Spain, while France observes the lowest switch rates between TNFs. The incidence of switches from TNFs to JAK inhibitors is more consistent across countries but remains highest in Germany.Figure 1.ConclusionThe introduction of small molecule agents in the EU over recent years (upadacitinib and filgotinib) has provided new options for the treatment of RA, creating a shift in the switching arena from TNF cycling to more utilization of alternate mechanisms of action post first line therapy in favor of JAK inhibitors.ReferencesNoneDisclosure of InterestsMaxine Yarnall: None declared, Peter C. Taylor Consultant of: Received consulting fees from AbbVie, Biogen, Eli Lilly, Fresenius, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Inc, Roche, and Sanofi., Grant/research support from: Received research grants from Celgene and Galapagos., Phil Pouliot: None declared, Emily Hettel: None declared, Kara Murray: None declared

The Arctic has warmed more than twice as fast as the global average since the mid 20th century, a phenomenon known as Arctic amplification (AA). These profound changes to the Arctic system have coincided with a period of ostensibly more frequent events of extreme weather across the Northern Hemisphere (NH) mid-latitudes, including extreme heat and rainfall events and recent severe winters. Though winter temperatures have generally warmed since 1960 over mid-to-high latitudes, the acceleration in the rate of warming at high-latitudes, relative to the rest of the NH, started approximately in 1990. Trends since 1990 show cooling over the NH continents, especially in Northern Eurasia. The possible link between Arctic change and mid-latitude climate and weather has spurred a rush of new observational and modeling studies. A number of workshops held during 2013–2014 have helped frame the problem and have called for continuing and enhancing efforts for improving our understanding of Arctic-mid-latitude linkages and its attribution to the occurrence of extreme climate and weather events. Although these workshops have outlined some of the major challenges and provided broad recommendations, further efforts are needed to synthesize the diversified research results to identify where community consensus and gaps exist. Building upon findings and recommendations of the previous workshops, the US CLIVAR Working Group on Arctic Change and Possible Influence on Mid-latitude Climate and Weather convened an international workshop at Georgetown University in Washington, DC, on February 1–3, 2017. Experts in the fields of atmosphere, ocean, and cryosphere sciences assembled to assess the rapidly evolving state of understanding, identify consensus on knowledge and gaps in research, and develop specific actions to accelerate progress within the research community. With more than 100 participants, the workshop was the largest and most comprehensive gathering of climate scientists to address the topic to date. In this white paper, we synthesize and discuss outcomes from this workshop and activities involving many of the working group members. WORKSHOP FINDINGS: RAPID ARCTIC CHANGE – EMERGENCE OF NEW FORCING (EXTERNAL AND INTERNAL) OF ATMOSPHERIC CIRCULATION: Rapid Arctic change is evident in the observations and is simulated and projected by global climate models. AA has been attributed to sea ice and snow decline (regionally and seasonally varying). However this cannot explain why AA is greatest in winter and weakest in summer. It was argued at the workshop that other factors can also greatly contribute to AA including: increased downwelling longwave radiation from greenhouse gases (including greater water vapor concentrations from local and remote sources); increasing ocean heat content, due to local and remote processes; regional and hemispheric atmospheric circulation changes; increased poleward heat transport in the atmosphere and ocean; and cloud radiative forcing. In particular, there is emerging observational evidence that an enhanced poleward transport of sensible and latent heat plays a very important role in the AA of the recent decades, and that this enhancement is mostly fueled by changes in the atmospheric circulation. We concluded that our understanding of AA is incomplete, especially the relative contributions from the different radiative, thermodynamic, and dynamic processes. ARCTIC MID-LATITUDE LINKAGES – FOCUSING ON SEASONAL AND REGIONAL LINKAGES AND ADDRESSING SOURCES OF INCONSISTENCY AND UNCERTAINTY AMONG STUDIES: The topic of Arctic mid-latitude linkages is controversial and was vigorously debated at the workshop. However, we concluded that rapid Arctic change is contributing to changes in mid-latitude climate and weather, as well as the occurrence of extreme events. But how significant the contribution is and what mechanisms are responsible are less well understood. Based on the synthesis efforts of observational and modeling studies, we identified a list of proposed physical processes or mechanisms that may play important roles in linking Arctic change to mid-latitude climate and weather. The list, ordered from high to low confidence, includes: increasing geopotential thickness over the polar cap; weakening of the thermal wind; modulating stratosphere-troposphere coupling; exciting anomalous planetary waves or stationary Rossby wave trains in winter and modulating transient synoptic waves in summer; altering storm tracks and behavior of blockings; and increasing frequency of occurrence of summer wave resonance. The pathway considered most robust is the propagation of planetary/Rossby waves excited by the diminished Barents-Kara sea ice, contributing to a northwestward expansion and intensification of the Siberian high leading to cold Eurasian winters. OPPORTUNITIES AND RECOMMENDATIONS: An important goal of the workshop was achieved: to hasten progress towards consensus understanding and identification of knowledge gaps. Based on the workshop findings, we identify specific opportunities to utilize observations and models, particularly a combination of them, to enable and accelerate progress in determining the mechanisms of rapid Arctic change and its mid-latitude linkages. OBSERVATIONS: Due to the remoteness and harsh environmental conditions of the Arctic, in situ observational time series are highly limited spatially and temporally in the region. 1. Synthesize new Arctic observations; 2. Create physically-based sea ice–ocean surface forcing datasets; 3. Systematically employ proven and new metrics; 4. Analyze paleoclimate data and new longer observational datasets; 5. Utilize new observational analysis methods that extend beyond correlative relationships; and 6. Consider both established and new theories of atmospheric and oceanic dynamics to interpret and guide observational and modeling studies. MODEL EXPERIMENTS: We acknowledge that models provide the primary tool for gaining a mechanistic understanding of variability and change in the Arctic and at mid-latitudes. Coordinated modeling studies should include approaches using a hierarchy of models from conceptual, simple component, or coupled models to complex atmospheric climate models or fully coupled Earth system models. We further recommend to force dynamical models with consistent boundary forcings. 1. Establish a Modeling Task Force to plan protocols, forcing, and output parameters for coordinated modeling experiments (Polar Amplification Model Intercomparison Project; PAMIP); 2. Furnish experiment datasets to the community through open access (via Earth System Grid); and 3. Promote analysis within the community of the coordinated modeling experiments to understand mechanisms for AA and to further understand pathways for Arctic mid-latitude linkages.

Background Depression and suicidality are well-described comorbidities in psoriasis (PSO). The prevalence of these comorbidities in psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) is less well described. Objectives To assess the prevalence of depression and suicidality in PsA and axSpA in the recent literature, and compare rates to PSO. Methods For PsA and axSpA, we evaluated the recent English-language literature identified through a PubMed search; we used a recent review and performed a targeted review of the period since the publication in order to establish the rates for PSO for comparison.1 Review articles were also examined to identify key publications. Results Rates of depression in PSO vary widely, depending on the outcome definition and method of ascertainment. Dowlatshahi et al. reported a pooled rate of 9.0–55.0%, with rates from the literature after the review period ranging from 9.0–39.8%. Rates for suicidality also varied widely, with 2.5–17.3% of patients (pts) reporting suicidal ideation. The limited data available provide ranges for depression in PsA of 3.4–28.6%, and in axSpA of 3.1–44.0%. The single study that differentiated between ankylosing spondylitis (AS) and non-radiographic (nr)-axSpA did not identify a difference between the two groups.2 Very limited data existed on suicidality in PsA and axSpA. For PsA, the incidence rates (IR) of suicidal ideation, attempts, and suicide per 1000 person-years in the UK were 0.4, 1.3, and Conclusions Although data are limited, rates of depression and suicidality in PsA and axSpA are comparable to those in PSO. Comparisons between studies and diseases are challenging due to a lack of standardized assessment tools and definitions of depression and suicidality. There are almost no data for nr-axSpA, which unlike AS has no gender predominance. Given that depression in PSO pts is more common in women,7 understanding the relative prevalence in AS versus nr-axSpA would be important. Generating additional data regarding the impact of depression and suicidality in PsA and axSpA should increase awareness among treating physicians. References Dowlatshahi EA. J. Invest Dermatol 2014;134:1542–51. Klic GE. Medicine (Baltimore) 2014;93:e337. Hagberg KW. Mod Rheumatol 2016;26:774–9. Chan CY. Int J Rheum Dis 2014; doi:10.1111/1756-185X.12456. Saygin C. Clin Exp Rheumatol 2015;33(6 Suppl 94):S30–5. Shen CC. J Rheumatol 2016;43:625–31. Lamb RC. Br J Dermatol 2016; doi:10.1111/bjd.14833. Disclosure of Interest A. Sheahan Employee of: UCB Pharma, R. Suruki Employee of: UCB Pharma, P. Taylor: None declared, V. Sloan Employee of: UCB Pharma

Mixed phase, hydrogenated amorphous and nanocrystalline silicon thin films grown by co-deposition (nanocrystals and amorphous material deposited sequentially in the same vacuum system) demonstrate pronounced quantum confinement effects. Based on photoluminescence measurements of co-deposited samples, we find evidence that the optical gap of nanocrystals embedded in hydrogenated amorphous silicon is increased to energies exceeding bulk crystalline silicon values – at least as high as 1.35 eV. The broad spectrum of emission of the nanocrystals is attributed to the size distribution and local fluctuations in matrix hydrogenation. The temperature dependence of this PL suggests that these nanocrystals possess fewer defects than those grown by conventional plasma enhanced chemical vapor deposition methods. Interactions between electronic states in nanocrystals and localized states in amorphous silicon matrix tissues are discussed in terms of their role in determining the strength of the quantum confinement potential.

Attitudes of four groups of professional educators are compared respecting the role of the superintendent in collective negotiations. The AFT sees him as head of the opposition's negotiating team. The NEA sees him as a member of the professional staff and as a neutral catalyst providing resource information while teacher representatives negotiate with a board committee. The AASA sees him in the dual role of chief executive and staff member, but also as an independent third party playing a significant role in the negotiation process. The NSBA sees him as the agent of the board and as a channel and interpreter of staff problems. Unresolved aspects of the superintendent's role include applying the separation-of-power principle to school board organization and joint decision making by the superintendent and the school board. (Authors/JK)

To effectively mitigate oxygen induced degradation of electronic properties in hydrogenated nanocrystalline silicon (nc-Si:H) the microscopic origins of the associated defects must be determined. This work elucidates the origin of a 0.7 eV photoluminescence (PL) band observed in thermally annealed, oxygen contaminated nc-Si:H. Raman and PL spectroscopy data demonstrate the deep defects responsible for the 0.7 eV PL reside in the crystalline phase. The electronic levels enabling the emission exist 0.4 eV below the conduction band edge, or 0.4 eV above the valence band edge, or both, with transitions into or out of extended states as opposed to band tail recombination. The defect formation energy is 0.6 eV, which suggests that the formation involves a local reconfiguration of oxygen and hydrogen as opposed to bulk diffusion. Hydrogen plays multiple roles in the microstructural evolution and electronic activity of these centers. TEM micrographs show dislocations in the nanocrystalline regions, which suggests that oxygen gettering occurs. It seems in the absence of hydrogen dislocations in Si nanocrystals scavenge oxygen impurities from grain boundaries to become optically active, enabling emission at 0.7 eV.

75 As NQR and high-field NMR experiments have been performed on Ge x As y Se 1− x − y glasses. Evolution of As bonding structure from arsenic sites with axially symmetric distribution of the electric field gradient (EFG) to highly asymmetric As surroundings has been revealed. Arsenic atoms form pyramidal structural units in Ge 2 As 2 Se 7 with no evidence of significant concentration of homopolar bonds. In Ge 2 As 2 Se 5 most of arsenic atoms form structural units with two As–As bonds per atom and asymmetric EFG distribution. Arsenic bondings become more complicated in Ge 0.33 As 0.12 Se 0.55 where all arsenic sites are highly distorted. The combination of NQR and NMR data provide valuable information on arsenic bonding dynamics in these glasses.

The local bonding structure in the Ge–As–Se ternary glassy system has been investigated by 75As nuclear quadrupole resonance (NQR) at 77 K. For the compositions with average coordination number r ¯ = 2.2 , 2.4 , 2.54 the NQR measurements yield no evidence for the presence of As–As homopolar bonds. For the composition Ge2As2Se5 ( r ¯ = 2.67 ) the NQR lineshape exhibits two peaks corresponding to arsenic sites with zero (or three) and two As–As bonds. High Ge and As content leads to formation of microclusters, where the predominant structural units are, possibly, As4Se4 molecules or partial molecules with As–As bonds. The NQR spectrum for the composition Ge0.33As0.12Se0.55 ( r ¯ = 2.78 ) shows a weak peak corresponding to an arsenic site with zero (or three) homobonds and two resolved peaks in the high frequency region. Such behavior is consistent with an increase in inhomogenity in the local structure and perhaps nanoscale phase separation.