In this work, the possibility of preparing cross-linked polypropylene (PP) via Diels–Alder (DA) chemistry is explored. The overall strategy involves reaction of maleated polypropylene (the starting material), furfuryl amine (FFA), and bismaleimide (BM) as the cross-linking agent. The occurrence of reversible cross-linking was studied by checking the presence of relevant peaks in FTIR spectra, i.e., CH out-of-plane bending vibrations of the furan ring’s peak (γCH) at an absorption band of 730–734 cm−1, CH=CH of the BM aromatic ring’s stretching vibrations (υCH=CH) at an absorption band of 1510 cm−1, and the DA adduct (C-O-C, δDAring) at an absorption band of 1186 cm−1. In agreement with the spectroscopic characterization, the presence of a cross-linked network is also confirmed by rheology, namely the higher storage modulus (G′) compared with loss modulus (G″) value (G′ >> G″), as obtained via temperature sweep. Both the maleic anhydride (MA) content as well as the annealing temperature (50 °C and 120 °C) favor the DA reaction, while only partial de-cross-linking (retro DA) is observed at the higher temperature range of 150–200 °C. In addition, the products show higher mechanical robustness and thermal stability compared to the starting material.

BackgroundEULAR Sjögren’s syndrome disease activity index (ESSDAI) assesses systemic disease activity in patients (pts) with primary Sjögren’s syndrome (pSS); however, weaknesses include exclusion of patient-reported symptoms, tear and salivary gland function, and a marked placebo (PBO) response. Composite of Relevant Endpoints for Sjögren’s Syndrome (CRESS) is a recently developed composite outcome measure validated using data from three Phase 3 randomised controlled trials of pts with pSS.1 Concise CRESS (cCRESS) is used when ocular staining score and salivary gland ultrasonography are unavailable. ESSDAI was an endpoint in a Phase 2, PBO-controlled study, evaluating the safety and efficacy of belimumab (BEL) and rituximab (RTX) sequential administration (BEL/RTX), and BEL and RTX monotherapies in pts with pSS. Although the results numerically favoured BEL/RTX over PBO, this was not statistically significant.ObjectivesTo evaluate the efficacy of BEL/RTX and monotherapies using cCRESS overall responses at Weeks (Wks) 24, 52, and 68, and individual item responses at Wk 24 in pts with pSS who completed the Phase 2 study.MethodsIn the Phase 2, double-blind, 68-Wk study (NCT02631538) adults were randomised (2:2:2:1) into 4 treatment arms: BEL/RTX (n=24; weekly BEL 200 mg subcutaneous [SC] to Wk 24 followed by weekly PBO SC to Wk 52 + RTX 1000 mg intravenous [IV], Wk 8 + 10), BEL monotherapy (n=24; weekly BEL 200 mg SC to Wk 52), RTX monotherapy (n=25; RTX 1000 mg IV, Wk 8 + 10), or PBO (n=13). Pts were classified post hoc as cCRESS responders when ≥3 of the following 5 items were met: 1) Clinical (Clin)ESSDAI score <5 (low disease state); 2) decrease of ≥1 point or ≥15% from baseline (BL) in EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI); 3) increase of ≥5 mm from BL in abnormal Schirmer’s test, or no change to abnormal if normal at BL; 4) unstimulated whole saliva (UWS) increase of ≥25% from BL, or any increase from BL if score was 0 at BL; 5) decrease of ≥25% in the rheumatoid factor (RF) titre from BL, or decrease of ≥10% in IgG from BL.1ResultsOf 86 randomised pts, 60 completed follow-up to Wk 68 (completer population) and were included in the analysis. Most pts were female (95%, n=57); mean (SD) age was 49.6 (13.0) years. BL disease characteristics are presented in the Table 1.Table 1.Clinical, functional, and laboratory parameters at BL and cCRESS responders at Wks 24, 52, and 68 (completer population)PBO (n=8)BEL/RTX (n=17)BEL (n=19)RTX (n=16)Pt parameters at BL, mean (SD)ClinESSDAI11.1 (3.76)11.7 (5.47)9.2 (3.77)11.7 (4.76)ESSPRI6.4 (2.05)6.0 (1.97)6.5 (1.68)5.9 (2.20)Schirmer, mm/5 min2.7 (3.25)5.3 (6.44)3.3 (3.16)2.8 (3.15)UWS, ml/min0.1 (0.11)0.1 (0.12)0.1 (0.09)0.1 (0.14)RF, KU/l60.8 (42.24)30.9 (38.20)37.0 (34.98)105.0 (200.97)IgG, g/l20.4 (6.65)16.7 (5.00)18.1 (7.19)16.5 (6.09)cCRESS responders, n (%)Wk 244 (50.0)9 (52.9)7 (36.8)5 (31.3)Wk 524 (50.0)10 (58.8)8 (42.1)4 (25.0)Wk 681 (12.5)6 (35.3)7 (36.8)3 (18.8)At Wks 24 and 52, the proportion of cCRESS responders was numerically higher with BEL/RTX than with either BEL, RTX, or PBO, but the difference was not significant (Table 1). At Wk 68, the proportion of cCRESS responders was numerically higher with BEL/RTX than with RTX or PBO (Table 1). The 5 cCRESS items contributed relatively equally to total cCRESS response, with the highest response observed in the RF/IgG item and the lowest in the tear gland item (Schirmer’s test; Figure 1).Figure 1.cCRESS and individual item responders at Wk 24 (completer population)ConclusionAt Wks 24, 52, and 68, BEL/RTX was generally associated with a numerically higher cCRESS response rate compared with the monotherapies or PBO. The PBO response for cCRESS was notable and similar to the PBO response for ClinESSDAI. The PBO response in the tear and salivary gland items was greater than in the other treatment arms, perhaps due to the use of cCRESS instead of CRESS. Due to the small sample size, the results should be interpreted with caution.References[1]Arends S, et al. Lancet Rheumatol 2021;3:553–62AcknowledgementsThis post hoc analysis of the GSK Study 201842 was funded by GlaxoSmithKline (GSK). Medical writing support was provided by Casmira Brazaitis, PhD, Fishawack Indicia Ltd, UK, part of Fishawack Health, and was funded by GSK.Disclosure of InterestsHendrika Bootsma Consultant of: BSM, Roche, Novartis, Medimmune and Union Chimique Belge, Grant/research support from: BSM and Roche, Suzanne Arends: None declared, Liseth de Wolff: None declared, Kenneth L Clark Shareholder of: GSK, Employee of: GSK, Andre van Maurik Shareholder of: GSK, Employee of: GSK, Prafull Mistry Shareholder of: GSK, Employee of: GSK, Pragya Shukla Shareholder of: GSK, Employee of: GSK, Svetlana Nihtyanova Shareholder of: GSK, Consultant of: Roche, Employee of: GSK, Norma Lynn Fox Shareholder of: GSK, Employee of: GSK, David Roth Shareholder of: GSK, Employee of: GSK

BackgroundPrimary Sjögren’s syndrome (pSS) has great impact on all aspects of patients’ lives, not only physically, but also mentally, socially and financially.1 Sicca symptoms are mainly treated with local treatment, but no systemic immunosuppressive treatment is registered yet for pSS, which may have significant consequences on whether patients find their symptom state acceptable (PASS). In a previous study, a cut-off for acceptable symptom state based on the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI, score <5) was developed for inclusion of patients with an unacceptable symptom state in clinical trials.2ObjectivesTo explore the presence of PASS in a standard of care cohort of pSS patients and to compare patient characteristics and disease activity including ESSPRI between patients with and without PASS.MethodsConsecutive outpatients with pSS from the REgistry of Sjögren Syndrome LongiTudinal (RESULT) cohort, who fulfilled the ACR/EULAR classification criteria and had available PASS data at baseline were included. Patient-reported outcomes were reported through questionnaires, which included the PASS (“Considering all the different ways your disease is affecting you, if you were to stay in this state for the next few months, do you consider your current state satisfactory?”; yes/no) and ESSPRI (“How severe has your dryness, fatigue and pain been during the last two weeks?”; scale 0-10). An acceptable ESSPRI symptom state has been defined as <5.2 Systemic disease activity was assessed with EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI). Independent samples t-test, Mann-Whitney U test or Chi Square test were used to analyse differences between patients with or without PASS.ResultsOf 277 included pSS patients, 248 (90%) were female, median age was 54 years (IQR 43-64) and disease duration 5 years (2-11). 198 (71%) patients scored their symptom state as acceptable according to PASS. Patients with PASS were significantly older and had a longer disease duration compared to patients without PASS. Furthermore, patients with PASS had more often a low disease activity according to ESSDAI, and less often moderate disease activity (Table 1). The difference in ESSDAI activity was mainly observed in the articular and constitutional domains. ESSPRI was significantly lower in patients with PASS (median 5 vs. 7). No differences were seen in functional or laboratory parameters (Table 1). Of all included patients, only 86 (31%) patients had an acceptable symptom state according to the pre-defined cut-off point for ESSPRI (score <5). Sensitivity and specificity of this ESSPRI cut-off point for reaching PASS was 40% and 92%, respectively.Table 1.Baseline characteristics of pSS patients with and without PASSPASS (n=198)Without PASS (n=79)Gender (female)177 (89)71 (90)Age (years)57 (44-65)*49 (41-60)*Disease duration (years)6 (2-12)*5 (2-8)*ESSDAI (total)4 (2-6) (n=191)4 (2-9) (n=75)<5127 (66)*38 (51)*5-1452 (27)*32 (43)*≥1412 (6)5 (7)ESSPRI (total)5 (4-7)**7 (6-8)**<580 (40)**6 (8)**Schirmer’s test (mm)4 (1-10) (n=179)4 (1-10) (n=72)Ocular staining score2 (1-4) (n=190)2 (0-4) (n=77)Unstimulated whole salivary flow (ml/min)0.05 (0.01-0.14) (n=187)0.08 (0.01-0.19) (n=76)Stimulated whole salivary flow (ml/min)0.54 (0.15-0.99) (n=189)0.58 (0.21-0.97) (n=76)SSA positive172/197 (87)66/79 (84)IgG (g/L)14 (11-19) (n=196)14 (10-19) (n=79)Rheumatoid factor (IU/ml)12 (3-39) (n=196)16 (2-47) (n=78)Data presented as median (IQR) or n (%)*Significant difference p<0.05***Significant difference p<0.001ConclusionThe majority (71%) of pSS patients reported being in an acceptable symptom state according to the PASS question in our standard of care cohort in daily clinical practice, despite high ESSPRI scores (60% with score ≥5). Further analyses of influences of treatment in these patients will be conducted.References[1]Vieira et al. Clin Exp Rheum 2021;39(Suppl. 133):S14-S16.[2]Seror et al. Ann Rheum Dis 2016;75:382-389.AcknowledgementsUnrestricted grants from the Dutch Arthritis Patients Association (ReumaNL), Bristol-Myers Squibb and NovartisDisclosure of InterestsLiseth de Wolff: None declared, Suzanne Arends: None declared, Esther Mossel: None declared, Greetje S. van Zuiden: None declared, Jolien F. van Nimwegen Speakers bureau: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Lisette Olie: None declared, Alja J. Stel: None declared, Konstantina Delli: None declared, Gwenny M. Verstappen: None declared, Frans G.M. Kroese: None declared, Arjan Vissink: None declared, Hendrika Bootsma Speakers bureau: Bristol Myers Squibb and Novartis, Consultant of: Bristol Myers Squibb, Roche, Novartis, Medimmune, Union Chimique Belge, Grant/research support from: Unrestricted grants from Bristol Myers Squibb and Roche