Response to: 'Correspondence on 'Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial'' by Cai and Peng response

Pathophysiology and treatment of rheumatic disease

The development of an optimal energy management system for vehicle electric power nets:a feasibility study from a control perspective

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The development of an optimal energy management system for vehicle electric power nets:a feasibility study from a control perspective

Confidential

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial

Objectives To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC).Methods Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) >= 2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive.Interventions (1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS = 30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed.Statistical analysis Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC.Results 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by >= 30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved euro472 compared with UC.Conclusion TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective.Pathophysiology and treatment of rheumatic disease

EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update

Objective To update the European League Against Rheumatism (EULAR) recommendations for the pharmacological treatment of psoriatic arthritis (PsA).Methods According to the EULAR standardised operating procedures, a systematic literature review was followed by a consensus meeting to develop this update involving 28 international taskforce members in May 2019. Levels of evidence and strengths of recommendations were determined.Results The updated recommendations comprise 6 overarching principles and 12 recommendations. The overarching principles address the nature of PsA and diversity of both musculoskeletal and non-musculoskeletal manifestations; the need for collaborative management and shared decision-making is highlighted. The recommendations provide a treatment strategy for pharmacological therapies. Non-steroidal anti-inflammatory drugs and local glucocorticoid injections are proposed as initial therapy; for patients with arthritis and poor prognostic factors, such as polyarthritis or monoarthritis/oligoarthritis accompanied by factors such as dactylitis or joint damage, rapid initiation of conventional synthetic disease-modifying antirheumatic drugs is recommended. If the treatment target is not achieved with this strategy, a biological disease-modifying antirheumatic drugs (bDMARDs) targeting tumour necrosis factor (TNF), interleukin (IL)-17A or IL-12/23 should be initiated, taking into account skin involvement if relevant. If axial disease predominates, a TNF inhibitor or IL-17A inhibitor should be started as first-line disease-modifying antirheumatic drug. Use of Janus kinase inhibitors is addressed primarily after bDMARD failure. Phosphodiesterase-4 inhibition is proposed for patients in whom these other drugs are inappropriate, generally in the context of mild disease. Drug switches and tapering in sustained remission are addressed.Conclusion These recommendations provide stakeholders with an updated consensus on the pharmacological management of PsA, based on a combination of evidence and expert opinion.Pathophysiology and treatment of rheumatic disease

ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update

Objectives To update the Assessment of SpondyloArthritis international Society (ASAS)-EULAR recommendations for the management of axial spondyloarthritis (axSpA). Methods Following the EULAR Standardised Operating Procedures, two systematic literature reviews were conducted on non-pharmacological and pharmacological treatment of axSpA. In a task force meeting, the evidence was presented, discussed, and overarching principles and recommendations were updated, followed by voting. Results Five overarching principles and 15 recommendations with a focus on personalised medicine were agreed: eight remained unchanged from the previous recommendations; three with minor edits on nomenclature; two with relevant updates (#9, 12); two newly formulated (#10, 11). The first five recommendations focus on treatment target and monitoring, non-pharmacological management and non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice pharmacological treatment. Recommendations 6-8 deal with analgesics and discourage long-term glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for pure axial involvement. Recommendation 9 describes the indication of biological DMARDs (bDMARDs, that is, tumour necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i)) and targeted synthetic DMARDs (tsDMARDs, ie, Janus kinase inhibitors) for patients who have Ankylosing Spondylitis Disease Activity Score >= 2.1 and failed >= 2 NSAIDs and also have either elevated C reactive protein, MRI inflammation of sacroiliac joints or radiographic sacroiliitis. Current practice is to start a TNFi or IL-17i. Recommendation 10 addresses extramusculoskeletal manifestations with TNF monoclonal antibodies preferred for recurrent uveitis or inflammatory bowel disease, and IL-17i for significant psoriasis. Treatment failure should prompt re-evaluation of the diagnosis and consideration of the presence of comorbidities (#11). If active axSpA is confirmed, switching to another b/tsDMARD is recommended (#12). Tapering, rather than immediate discontinuation of a bDMARD, can be considered in patients in sustained remission (#13). The last recommendations (#14, 15) deal with surgery and spinal fractures. Conclusions The 2022 ASAS-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA

Barley acyl carrier protein: its amino acid sequence and assay using purified malonyl-CoA:ACP transacylase

Malonyl-CoA:ACP transacylase from barley (Hordeum vulgare L.) has been purified to homogeneity and used in an assay for acyl carrier protein (ACP). The transacylase is an acidic, monomeric protein with a molecular weight of 34,500 very similar to the analogous E. coli enzyme. A heat and acid stable acyl carrier protein from barley has been purified to homogeneity and its chemical composition determined. The ACP consists of a continuous stretch of the following 72 amino acids H2N-A-A-M-G-E-A-Q-A-K-K-E-T-V-D-K-V-(C?)-M-I-V-K-K-Q-L-A-V-P-D-G-T-P-V-T-A-E-S-K-F-S-E-L-G-A-D-S-L-D-T-V-E-I-V-M-G-L-E-E-E-F-N-I-T-V-D-E-T-S-A-Q-D-I-A72...A87-COOH. A comparison of the primary structure of this plant ACP and bacterial ACP reveals two identical sequences (underlined) in the midregion of the molecule containing the 4′-phosphopantetheine attachment site, while differences occur outside this region. Nine extra residues (italicized) are present at the N-terminal end of the barley protein thereby accounting for its larger size. Identical products are obtained when barley chloroplast fatty acid synthetase is incubated with either barley or E. coli ACP, but the latter is twice as active as the former in fatty acid synthesis. The possible significance of the N-terminal part of the ACP is discussed in relation to the reported differences in biochemical activities of plant and bacterial ACPs