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Abstract Background Many effective treatments for nicotine addiction inhibit noradrenaline reuptake. Three recent studies have suggested that another noradrenaline reuptake inhibitor, atomoxetine, may reduce smoking behaviors. Methods The present double-blind, placebo-controlled, fixed-dose study was carried out over 21 days during which administration of 40 mg atomoxetine was compared to placebo in 17 individuals. Of these, nine were randomized to atomoxetine and eight to placebo. Baseline and weekly measurements were made using the Cigarette Dependence Scale (CDS), Cigarette Withdrawal Scale (CWS), Questionnaire of Smoking Urges (QSU), reported number of cigarettes smoked, and salivary cotinine levels. Results The study results showed that all those on placebo completed the study. In marked contrast, of the nine individuals who started on atomoxetine, five dropped out due to side effects. In a completer analysis there were statistically significant differences at 14 and 21 days in several measures between the atomoxetine and placebo groups, including CDS, CWS, QSU, number of cigarettes smoked (decreasing to less than two per day in the treatment group who completed the study), and a trend towards lower mean salivary cotinine levels. However, these differences were not seen in a last observation carried forward (LOCF) analysis. Conclusions In summary, this is the first study to examine the use of atomoxetine in non-psychiatric adult smokers for a period of more than 7 days, and the findings suggest that atomoxetine might be a useful treatment for nicotine addiction. However, the dose used in the current study was too high to be tolerated by many adults, and a dose-finding study is required to determine the most appropriate dose for future studies of this potential treatment for smoking cessation.

Objective: We aimed to assess: 1. The frequency of axial spondyloarthritis (axSpA) according to extra-articular presentation and HLA-B27 status; 2. Clinical and imaging features that distinguish axSpA from non-axSpA; 3. The impact of MRI on diagnosis and classification of axSpA., Methods: The Screening in Axial Spondyloarthritis in Psoriasis, Iritis, Colitis, (SASPIC) study enrolled patients in two multicenter cohorts. Consecutive patients with undiagnosed chronic back pain attending dermatology, ophthalmology, and gastroenterology clinics with PsO, AAU, or IBD, were referred to a local rheumatologist with special expertise in axSpA for a structured diagnostic evaluation. The primary outcome was proportion of patients diagnosed with axSpA by final global evaluation., Results: Frequency of axSpA was 46.7%, 61.6%, and 46.8% in SASPIC-1 cases (n=212) and 23.5%, 57.9%, and 23.3% in SASPIC-2 cases (n=151) with PsO, AAU, or IBD, respectively. Among B27 positives, axSpA was diagnosed in 70%, 74.5%, and 66.7% in SASPIC-1, and in 71.4%, 87.8%, and 55.6% in SASPIC-2 in patients with PsO, AAU, or IBD, respectively. All musculoskeletal clinical features were non-discriminatory. MRI was indicative of axSpA in 60-80% of patients and MRI in all patients (SASPIC-2) versus on-demand (SASPIC-1) led to 25% fewer diagnoses of axSpA in HLA B27 negatives with PsO or IBD. Performance of the ASAS classification criteria was greater with routine MRI (SASPIC-2) though sensitivity was lower than previously reported., Conclusions: Optimal management of patients presenting with PsO, AAU, IBD, and undiagnosed chronic back pain should include referral to a rheumatologist. Conducting MRI in all patients enhances diagnostic accuracy., (This article is protected by copyright. All rights reserved.)

Objective: To assess whether using ultrasound (US) in addition to clinical information versus only clinical information in a treat-to-target (T2T) strategy leads to more clinical remission and to less radiographic progression in RA., Methods: Patients with RA from the 2-year prospective BIODAM cohort were included. Clinical and US data (US7-score) were collected every 3 months and hands and feet radiographs every 6 months. At each visit, it was decided whether patients were treated according to the clinical definition of T2T with DAS44 remission as benchmark (T2T-DAS44). T2T-DAS44 was correctly applied if: (i) DAS44 remission had been achieved or (ii) if not, treatment was intensified. A T2T strategy also considering US data (T2T-DAS44-US) was correctly applied if: (i) both DAS44 and US remission (synovitis-score < 2, Doppler-score = 0) were present; or (ii) if not, treatment was intensified. The effect of T2T-DAS44-US on attaining clinical remission and on change in Sharp-van der Heijde score compared to T2T-DAS44 was analysed., Results: A total of 1016 visits of 128 patients were included. T2T-DAS44 was correctly followed in 24% of visits and T2T-DAS44-US in 41%. DAS44 < 1.6 was achieved in 39% of visits. Compared to T2T-DAS44, using the T2T-DAS44-US strategy resulted in a 41% lower likelihood of DAS44 remission [OR (95% CI): 0.59 (0.40;0.87)] and had no effect on radiographic progression [β(95% CI): 0.11 (- 0.16;0.39)] assessed at various intervals up to 12 months later., Conclusion: Our results do not suggest a benefit of using the US7-score in addition to clinical information as a T2T benchmark compared to clinical information alone. Key Points • Ultrasound has a valuable role in diagnostic evaluation of rheumatoid arthritis, but it is unclear whether adding ultrasound to the clinical assessment in a treat-to-target (T2T) strategy leads to more patients achieving remission and reduction in radiographic progression. • Our data from a real-world study demonstrated that adding information from ultrasound to the clinical assessment in a T2T strategy led to a lower rather than a higher likelihood of obtaining clinical remission as compared to using only clinical assessment. • Our data demonstrated that adding ultrasound data to a T2T strategy based only on clinical assessment did not offer additional protection against radiographic progression in patients with RA. • Adding US to a T2T strategy based on clinical assessment led to far more treatment intensifications (with consequences for costs and exposure to adverse events) without yielding a meaningful clinical benefit., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objectives: To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active RA who start (new) DMARD-therapy., Methods: Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of two visits). The relation between T2T intensity and change in SvdH-score was modelled by generalized estimating equations., Results: In total, 511 patients were included [mean (s.d.) age: 56 (13) years; 76% female]. Mean 2-year SvdH progression was 2.2 (4.1) units (median: 1 unit). A stricter application of T2T in a 3-month interval did not reduce progression in the same 6-month interval [parameter estimates (for yes vs no): +0.15 units (95% CI: -0.04, 0.33) for 2 vs 0 visits; and +0.08 units (-0.06; 0.22) for 1 vs 0 visits] nor did it reduce progression in the subsequent 6-month interval., Conclusions: In this daily practice cohort, following T2T principles more meticulously did not result in less radiographic progression than a somewhat more lenient attitude towards T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Compelling evidence supports a treat-to-target (T2T) strategy for optimal outcomes in rheumatoid arthritis (RA). There is limited knowledge regarding the factors that impede implementation of T2T, particularly in a setting where adherence to T2T is protocol-specified. We aimed to assess clinical factors that associate with failure to adhere to T2T., Methods: Patients with RA from 10 countries who were starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required per protocol to adhere to the T2T strategy. Factors influencing adherence to T2T low disease activity (T2T-LDA; 44-joint count Disease Activity Score ≤ 2.4) were analyzed in 2 types of binomial generalized estimating equations models: (1) including only baseline features (baseline model); and (2) modeling variables that inherently vary over time as such (longitudinal model)., Results: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. Failure of adherence to T2T-LDA was noted in 1765 visits (40.5%). In the baseline multivariable model, a high number of comorbidities (OR 1.10, 95% CI 1.02-1.19), smoking (OR 1.32, 95% CI 1.08-1.63) and high number of tender joints (OR 1.03, 95% CI 1.02-1.04) were independently associated with failure to implement T2T, while anticitrullinated protein antibody/rheumatoid factor positivity (OR 0.63, 95% CI 0.50-0.80) was a significant facilitator of T2T. Results were similar in the longitudinal model., Conclusion: Lack of adherence to T2T in the RA BIODAM cohort was evident in a substantial proportion despite being a protocol requirement, and this could be predicted by clinical features. [Rheumatoid Arthritis (RA) BIODAM cohort; ClinicalTrials.gov: NCT01476956].

Objective: The Outcome Measures in Rheumatology Soluble Biomarker Working Group initiated an international, multicenter, prospective study, the Rheumatoid Arthritis (RA) BIODAM cohort, to generate resources for the clinical validation of candidate biomarkers predictive of radiographic progression. This first report describes the cohort, clinical outcomes, and radiographic findings., Methods: Patients with RA from 38 sites in 10 countries starting or changing conventional synthetic disease-modifying antirheumatic drugs and/or starting tumor necrosis factor inhibitors were followed for 2 years. Participating physicians were required to adhere to a treat-to-target strategy. Biosamples (serum, urine) were acquired every 3 months, radiography of hands and feet every 6 months, and ultrasound of hands and feet every 3 months in a subset. Primary endpoint was radiographic progression by the Sharp/van der Heijde score., Results: A total of 571 patients were recruited and 439 (76.9%) completed 2-year followup. At baseline, the majority was female (76%), mean age 55.7 years, and mean disease duration 6.5 years. Patients had a mean of 8.4 swollen and 13.6 tender joints, 44-joint count Disease Activity Score (DAS44) 3.8, 77.7% rheumatoid factor-positive or anticitrullinated protein antibody-positive. Percentage of patients in DAS and American College of Rheumatology remission at 2 years was 52.2% and 27.1%, respectively. Percentage of patients with radiographic progression (> 0.5) at 1 and 2 years was 38.2% and 59.9%, respectively., Conclusion: The RA BIODAM prospective study succeeded in generating an extensive list of clinical, imaging (2343 radiographs), and biosample (4638 sera) resources that will be made available to expedite the identification and validation of biomarkers for radiographic damage endpoints. (Clinicaltrials.gov: NCT01476956, clinicaltrials.gov/ct2/show/NCT01476956).

Objectives: To investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target., Methods: RA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 <1.6) as the target. Sustained T2T was defined as T2T followed in ≥2 consecutive visits. The main outcome was the achievement of DAS44 remission at the subsequent 3-month visit. Other outcomes were remission according to 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definitions. The association between T2T and remission was tested in generalised estimating equations models., Results: In total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52)., Conclusion: In daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission., Competing Interests: Competing interests: SR: Received research grants and/or consultancy fees from AbbVie, Eli Lilly, MSD, Novartis and Sanofi. RL: Received consulting fees from AbbVie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Roche, UCB and is Director of Rheumatology Consultancy BV. DvdH: Received consulting fees from AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma and is Director of Imaging Rheumatology BV. AS: Received speaking fees from Novartis. OFG: Received research grants and/or consultancy fees from AbbVie, Eli Lilly, Celgene, Novartis, UCB, Pfizer, Amgen and Janssen. MØ: Received research support, consultancy fees and/or speaker fees form Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB. OE: Received grants and personal fees from Pfizer, Abbvie, Roche, Janssen, Novartis and Lilly. JCT: Received research grants and/or consulting fees from AbbVie, Amgen, Celgene, Centocor, Lilly, Medexux/Medac, Merck, Novartis, Pfizer, Sandoz and Sanofi. ML: Received advisory board honoraria from AbbVie, Actelion, Boehringer Ingelheim, BMS, Janssen, Novartis, Pfizer, Sanofi, Roche and an unrestricted educational grant from AbbVie. GF: Received research grants and/or consultancy fees from Novartis, Roche, BMS, Pfizer, AbbVie, Lilly, Janssen, MSD, Boehringer-Ingelheim and UCB. MB: Received research grants from AbbVie Co.KG, Roche, Novartis and Pfizer; received speaking fees from Actelion, AbbVie Co.KG, BMS, Celgene, Gilead, Janssen, Lilly, MSD, Novartis, Sanofi Genzyme, Roche, Pfizer and UCB. GB: Received consulting fees from Eli Lilly, Janssen, Novartis and Pfizer; received speaker fees from BMS, Merck and Pfizer. Industry support for investigator-initiated research initiatives from Abbvie, Amgen, BMS, Celgene, Eli Lilly, Jannsen, Merck, Pfizer, Roche and UCB. BC: Received consulting fees from AbbVie, BMS, Eli-Lilly, Gilead, Janssen, Merck, Novartis, Pfizer, Roche-Chugai, Sanofi and UCB. TS: Received consulting fees from Lilly, Novartis, Pfizer and Sanofi; received research financial support from Pfizer and Lilly. AS: Received research grants and/or consultancy fees from AbbVie, BMS, Chugai, Eli Lilly, MSD, Nordic pharma, Novartis, Pfizer, Sanofi and UCB. MD: Received research grants and/or honorarium fees for his participation at advisory boards and/or symposium organised by Pfizer, AbbVie, Lilly, Novartis, BMS, Roche, UCB and Merck. MR: Received advisory board honoraria, consultancy fees and/or speaker fees from Abiogen, Amgen, Abbvie, BMS, Celgene, Eli-Lilly, MSD, Novartis, Pfizer, Sanofi, Sandoz and UCB. MG: Received advisory board honoraria, consultancy fees and/or speaker fees from Abbvie, Alfa-Sigma, BMS, Celgene, MSD, Novartis, Pfizer, Roche and Sanofi. LS: Received speaker fees from Amgen,Eli Lilly, Abbvie, Roche and BMS. AGC: Received consultancy fees from BMS, Chugai, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Sanofi, UCB, AbbVie, Celgene and Nordic Pharma; received research grants from Pfizer, UCB, AbbVie and Celgene. CB: Received advisory board honoraria from Gilead, Pfizer, Novartis, Eli Lily, Roche and Amgen; speaking fees from UCB, BMS and Abbvie. COB III: Consultant to Abbvie, BMS, Gilead, Lilly, Pfizer, Genentech/Roche and Sanofi/Regeneron. Grant support from BMS and Janssen. PPT: Currently an employee of Kintai Therapeutics, Cambridge MA. Kintai Therapeutics has not been involved in this work. HBH: Received fees for speaking and/or consulting from AbbVie, BMS, Pfizer, UCB, Roche, MSD and Novartis. WPM: Received consulting fees from AbbVie, Boehringer Ingelheim, Celgene, Eli-Lilly, Galapagos, Janssen, Novartis, Pfizer and UCB Pharma and is Chief Medical Officer of CARE Arthritis Limited., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Atomoxetine has been approved for the treatment of attention deficit/hyperactivity disorder in both adults and children. However, it is also being examined for several off-label uses in adults including mood disorders, eating disorders, cognitive dysfunction, and the treatment of addictions. Prior to such use it is important to examine the reported adverse events to see if this represents an appropriate level of risk. This is particularly important in the light of recent warnings from several regulatory bodies about an increase in blood pressure in a significant percentage of patients taking atomoxetine. To understand the risks a literature review was performed, and which identified the following potential problems. The first is that this drug should not be given in patients with known cardiovascular problems, and that all adult patients who receive atomoxetine should be monitored for changes in blood pressure throughout treatment. Secondly, there are several clinical situations in which atomoxetine should be closely monitored, or avoided, including patients who have a history or risk of narrow angle glaucoma, epileptic seizures, Tourette's syndrome, a history of urinary outflow obstruction, or who are pregnant or lactating. In conclusion, the current literature suggests that atomoxetine can be safely used off-label provided the above precautions are taken.