Points to consider: EULAR-UEMS standards for the training of European rheumatologists.

BACKGROUND: Postgraduate rheumatology training programmes are already established at a national level in most European countries. However, previous work has highlighted a substantial level of heterogeneity in the organisation and, in part, content of programmes. OBJECTIVE: To define competences and standards of knowledge, skills and professional behaviours required for the training of rheumatologists. METHODS: A European Alliance of Associations for Rheumatology (EULAR) task force (TF) of 23 experts, including two members of the European Union of Medical Specialists (UEMS) section of rheumatology, was convened. The mapping phase consisted of the retrieval of key documents on specialty training in rheumatology and other related specialties across a broad set of international sources. The content of these documents was extracted and represented the foundation for the document draft that underwent several rounds of online discussion within the TF, and afterwards was also distributed to a broad group of stakeholders for collecting feedback. The list of generated competences was voted on during the TF meetings, while the level of agreement (LoA) with each statement was established by anonymous online voting. RESULTS: A total of 132 international training curricula were retrieved and extracted. In addition to the TF members, 253 stakeholders commented and voted on the competences through an online anonymous survey. The TF developed (1) an overarching framework indicating the areas that should be addressed during training, (2) 7 domains defining broad areas that rheumatology trainees should master by the end of the training programme, (3) 8 core themes defining the nuances of each domain and (4) 28 competences that trainees should acquire to cover each of the areas outlined in the overarching framework. A high LoA was achieved for all competences. CONCLUSION: These points to consider for EULAR-UEMS standards for the training of European rheumatologists are now defined. Their dissemination and use can hopefully contribute to harmonising training across European countries.

[Incidental finding aortitis: how to handle it?] / Découverte fortuite d'une aortite : quelle prise en charge ?

Aortitis may be an incidental finding at imaging. It refers to inflammation of the aortic wall and sometimes may be hard to differentiate with the periaortitis, inflammation of tissues around the vessel. Their clinical presentation is as varied as their etiologies. Appropriate early management is essential for improving patient prognosis, as the diagnostic approach remains challenging.

Une aortite, inflammation de la paroi de l'aorte, est parfois décrite à l'imagerie. Elle peut être confondue avec une périaortite, l'inflammation des tissus autour du vaisseau. La présentation clinique de ces deux atteintes est aussi diverse que leurs causes. Comme la prise en charge thérapeutique adéquate dépend de la maladie sous-jacente, un choix réfléchi d'examens paracliniques est essentiel pour améliorer le pronostic du patient.

Comparison of drug retention of TNF inhibitors, other biologics and JAK inhibitors in RA patients who discontinued JAK inhibitor therapy.

OBJECTIVES: JAK Inhibitors (JAKi) are recommended DMARDs for patients with moderate-to-severe RA who failed first-line therapy with methotrexate. There is a lack of data allowing an evidence-based choice of subsequent DMARD therapy for patients who had discontinued JAKi treatment. We aimed to compare the effectiveness of TNF inhibitor (TNFi) therapy vs JAKi vs other mode of action (OMA) biologic DMARD (bDMARD) in RA patients who were previously treated with a JAKi. METHODS: RA patients who discontinued JAKi treatment within the Swiss RA registry SCQM were included for this observational prospective cohort study. The primary outcome was drug retention for either TNFi, OMA bDMARD or JAKi. The hazard ratio for treatment discontinuation was calculated adjusting for potential confounders. A descriptive analysis of the reasons for discontinuation was performed. RESULTS: Four hundred treatment courses of JAKi were included, with a subsequent switch to either JAKi, TNFi or OMA bDMARD. The crude overall drug retention was higher in patients switching to another JAKi as compared with TNFi and comparable to OMA. A significant difference of JAKi vs TNFi persisted after adjusting for potential confounders. CONCLUSION: In a real-world population of RA patients who discontinued treatment with a JAKi, switching to another JAKi resulted in a higher drug retention than switching to a TNFi. A switch to a second JAKi seems an effective therapeutic option.

2019 EULAR points to consider for the assessment of competences in rheumatology specialty training.

BACKGROUND AND AIM: Striving for harmonisation of specialty training and excellence of care in rheumatology, the European League Against Rheumatism (EULAR) established a task force to develop points to consider (PtCs) for the assessment of competences during rheumatology specialty training. METHODS: A systematic literature review on the performance of methods for the assessment of competences in rheumatology specialty training was conducted. This was followed by focus groups in five selected countries to gather information on assessment practices and priorities. Combining the collected evidence with expert opinion, the PtCs were formulated by the multidisciplinary task force, including rheumatologists, medical educationalists, and people with rheumatic and musculoskeletal diseases. The level of agreement (LoA) for each PtC was anonymously voted online. RESULTS: Four overarching principles and 10 PtCs were formulated. The overarching principles highlighted the importance of assessments being closely linked to the rheumatology training programme and protecting sufficient time and resources to ensure effective implementation. In the PtCs, two were related to overall assessment strategy (PtCs 1 and 5); three focused on formative assessment and portfolio (PtCs 2-4); three focused on the assessment of knowledge, skills or professionalism (PtCs 6-8); one focused on trainees at risk of failure (PtC 9); and one focused on training the trainers (PtC 10). The LoA (0-10) ranged from 8.75 to 9.9. CONCLUSION: These EULAR PtCs provide European guidance on assessment methods throughout rheumatology training programmes. These can be used to benchmark current practices and to develop future strategies, thereby fostering continuous improvement in rheumatology learning and, ultimately, in patient care.

[Methotrexate use: untangling the real from the fake]. / Utilisation du méthotrexate : démêler le vrai du faux.

Methotrexate is one of the most important treatments for rheumatologists, however often of great concern to the non-specialist. This article reviews some useful aspects to know, in terms of safety with no major infectious risk or risk of pulmonary fibrosis, but also the benefits of using the subcutaneous route, the addition of low dose folic acid, the association with hydroxychloroquine or a short stop with flu vaccination, practical elements to demystify a safe and useful treatment.

Le méthotrexate est l'un des traitements incontournables du rhumatologue, suscitant toutefois de nombreuses inquiétudes chez le non-spécialiste. Cet article révise quelques notions utiles à connaître, comme l'absence de risque infectieux majeur ou de fibrose pulmonaire, les avantages associés à l'utilisation de la voie sous-cutanée, l'ajout de faible dose d'acide folique, l'association à l'hydroxychloroquine ou un court arrêt lors de la vaccination antigrippe, des éléments pratiques pour démystifier un traitement sûr et utile.

The Global Spine Care Initiative: a systematic review for the assessment of spine-related complaints in populations with limited resources and in low- and middle-income communities.

PURPOSE: The purpose of this systematic literature review was to develop recommendations for the assessment of spine-related complaints in medically underserved areas with limited resources. METHODS: We conducted a systematic review and best evidence synthesis of guidelines on the assessment of spine-related complaints. Independent reviewers critically appraised eligible guidelines using the Appraisal of Guidelines for Research and Evaluation-II criteria. Low risk of bias clinical practice guidelines was used to develop recommendations. In accordance with the mandate of the Global Spinal Care Initiative (GSCI), recommendations were selected that could be applied to medically underserved areas and low- and middle-income countries by considering the limited access and costs of diagnostic technologies. RESULTS: We screened 3069 citations; 20 guidelines were eligible for critical appraisal. We used 13 that had a low risk of bias that targeted neck and back pain. CONCLUSIONS: When assessing patients with spine-related complaints in medically underserved areas and low- and middle-income countries, we recommend that clinicians should: (1) take a clinical history to determine signs or symptoms suggesting serious pathology (red flags) and psychological factors (yellow flags); (2) perform a physical examination (musculoskeletal and neurological); (3) do not routinely obtain diagnostic imaging; (4) obtain diagnostic imaging and/or laboratory tests when serious pathologies are suspected, and/or presence of progressive neurologic deficits, and/or disabling persistent pain; (5) do not perform electromyography or nerve conduction studies for diagnosis of intervertebral disc disease with radiculopathy; and (6) do not perform discography for the assessment of spinal disorders. This information can be used to inform the GSCI care pathway and model of care. These slides can be retrieved under Electronic Supplementary Material.

The Global Spine Care Initiative: model of care and implementation.

PURPOSE: Spine-related disorders are a leading cause of global disability and are a burden on society and to public health. Currently, there is no comprehensive, evidence-based model of care for spine-related disorders, which includes back and neck pain, deformity, spine injury, neurological conditions, spinal diseases, and pathology, that could be applied in global health care settings. The purposes of this paper are to propose: (1) principles to transform the delivery of spine care; (2) an evidence-based model that could be applied globally; and (3) implementation suggestions. METHODS: The Global Spine Care Initiative (GSCI) meetings and literature reviews were synthesized into a seed document and distributed to spine care experts. After three rounds of a modified Delphi process, all participants reached consensus on the final model of care and implementation steps. RESULTS: Sixty-six experts representing 24 countries participated. The GSCI model of care has eight core principles: person-centered, people-centered, biopsychosocial, proactive, evidence-based, integrative, collaborative, and self-sustaining. The model of care includes a classification system and care pathway, levels of care, and a focus on the patient's journey. The six steps for implementation are initiation and preparation; assessment of the current situation; planning and designing solutions; implementation; assessment and evaluation of program; and sustain program and scale up. CONCLUSION: The GSCI proposes an evidence-based, practical, sustainable, and scalable model of care representing eight core principles with a six-step implementation plan. The aim of this model is to help transform spine care globally, especially in low- and middle-income countries and underserved communities. These slides can be retrieved under Electronic Supplementary Material.

The Global Spine Care Initiative: methodology, contributors, and disclosures.

PURPOSE: The purpose of this report is to describe the Global Spine Care Initiative (GSCI) contributors, disclosures, and methods for reporting transparency on the development of the recommendations. METHODS: World Spine Care convened the GSCI to develop an evidence-based, practical, and sustainable healthcare model for spinal care. The initiative aims to improve the management, prevention, and public health for spine-related disorders worldwide; thus, global representation was essential. A series of meetings established the initiative's mission and goals. Electronic surveys collected contributorship and demographic information, and experiences with spinal conditions to better understand perceptions and potential biases that were contributing to the model of care. RESULTS: Sixty-eight clinicians and scientists participated in the deliberations and are authors of one or more of the GSCI articles. Of these experts, 57 reported providing spine care in 34 countries, (i.e., low-, middle-, and high-income countries, as well as underserved communities in high-income countries.) The majority reported personally experiencing or having a close family member with one or more spinal concerns including: spine-related trauma or injury, spinal problems that required emergency or surgical intervention, spinal pain referred from non-spine sources, spinal deformity, spinal pathology or disease, neurological problems, and/or mild, moderate, or severe back or neck pain. There were no substantial reported conflicts of interest. CONCLUSION: The GSCI participants have broad professional experience and wide international distribution with no discipline dominating the deliberations. The GSCI believes this set of papers has the potential to inform and improve spine care globally. These slides can be retrieved under Electronic Supplementary Material.

The Global Spine Care Initiative: World Spine Care executive summary on reducing spine-related disability in low- and middle-income communities.

PURPOSE: Spinal disorders, including back and neck pain, are major causes of disability, economic hardship, and morbidity, especially in underserved communities and low- and middle-income countries. Currently, there is no model of care to address this issue. This paper provides an overview of the papers from the Global Spine Care Initiative (GSCI), which was convened to develop an evidence-based, practical, and sustainable, spinal healthcare model for communities around the world with various levels of resources. METHODS: Leading spine clinicians and scientists around the world were invited to participate. The interprofessional, international team consisted of 68 members from 24 countries, representing most disciplines that study or care for patients with spinal symptoms, including family physicians, spine surgeons, rheumatologists, chiropractors, physical therapists, epidemiologists, research methodologists, and other stakeholders. RESULTS: Literature reviews on the burden of spinal disorders and six categories of evidence-based interventions for spinal disorders (assessment, public health, psychosocial, noninvasive, invasive, and the management of osteoporosis) were completed. In addition, participants developed a stratification system for surgical intervention, a classification system for spinal disorders, an evidence-based care pathway, and lists of resources and recommendations to implement the GSCI model of care. CONCLUSION: The GSCI proposes an evidence-based model that is consistent with recent calls for action to reduce the global burden of spinal disorders. The model requires testing to determine feasibility. If it proves to be implementable, this model holds great promise to reduce the tremendous global burden of spinal disorders. These slides can be retrieved under Electronic Supplementary Material.

Pharmaceutical-grade Chondroitin sulfate is as effective as celecoxib and superior to placebo in symptomatic knee osteoarthritis: the ChONdroitin versus CElecoxib versus Placebo Trial (CONCEPT).

OBJECTIVES: Chondroitin sulfate 800 mg/day (CS) pharmaceutical-grade in the management of symptomatic knee osteoarthritis consistent with the European Medicines Agency guideline. METHODS: A prospective, randomised, 6-month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day)-controlled trial assessing changes in pain on a Visual Analogue Scale (VAS) and in the Lequesne Index (LI) as coprimary endpoints. Minimal-Clinically Important Improvement (MCII), Patient-Acceptable Symptoms State (PASS) were used as secondary endpoints. RESULTS: 604 patients (knee osteoarthritis) diagnosed according to American College of Rheumalogy (ACR) criteria, recruited in five European countries and followed for 182 days. CS and celecoxib showed a greater significant reduction in pain and LI than placebo. In the intention-to-treat (ITT) population, pain reduction in VAS at day 182 in the CS group (-42.6 mm) and in celecoxib group (-39.5 mm) was significantly greater than the placebo group (-33.3 mm) (p=0.001 for CS and p=0.009 for celecoxib), while no difference observed between CS and celecoxib. Similar trend for the LI, as reduction in this metric in the CS group (-4.7) and celecoxib group (-4.6) was significantly greater than the placebo group (-3.7) (p=0.023 for CS and p=0.015 for celecoxib), no difference was observed between CS and celecoxib. Both secondary endpoints (MCII and PASS) at day 182 improved significantly in the CS and celecoxib groups. All treatments demonstrated excellent safety profiles. CONCLUSION: A 800 mg/day pharmaceutical-grade CS is superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in symptomatic knee osteoarthritis (OA) patients. This formulation of CS should be considered a first-line treatment in the medical management of knee OA.

Female hormonal factors and the development of anti-citrullinated protein antibodies in women at risk of rheumatoid arthritis.

Objectives: To analyse the association between female hormonal factors and the development of systemic autoimmunity associated with RA in women at increased risk for RA, namely first-degree relatives of patients with RA (RA-FDRs). Methods: In an ongoing cohort study of RA-FDRs, we analysed all women with available ACPA status. The primary outcome was ACPA positivity. The predictors of interest were female hormonal factors, such as oral contraceptives, breastfeeding, post-menopausal status, early post-menopausal period and total number of ovulatory years. Results: A total of 768 female RA-FDRs were analysed, of which 42 (5%) had developed ACPA positivity. ACPA-positive women were older (52 vs 44 years, P = 0.001). Hormonal factors significantly and independently associated with the presence of ACPA were the post-menopausal (P < 0.001) and the early post-menopausal periods (P = 0.040). Conclusions: In women at increased risk of RA, characteristic systemic autoimmunity was associated with menopause, suggesting that the acute decline in ovarian function might contribute to the development of autoimmunity associated with RA and potentially to the increased risk of RA in women.

Efficacy, Safety and Mucosal Healing of Methotrexate in a Large Longitudinal Cohort of Inflammatory Bowel Disease Patients.

BACKGROUND/AIMS: Evidence for the effectiveness of methotrexate (MTX) in treating inflammatory bowel disease (IBD) is still incomplete. This study assessed the effectiveness, safety and mucosal healing in IBD patients treated with MTX in the Swiss IBD Cohort. METHODS: Efficacy was defined by physician assessment or by CD activity index <150 points for Crohn's disease (CD) or Modified Truelove and Witts activity index <4 points for ulcerative colitis (UC), measured at least after 3 months of MTX therapy. Mucosal healing was evaluated after 3 months or more of therapy. RESULTS: MTX was administered to 341 patients (262 CD; 79 UC) out of 2,660 patients. MTX effectiveness was 59.5% (128/215) in CD and 40.0% (24/60) in UC (chi2 = 7.2409, p = 0.007). Among patients on MTX therapy at the time of analysis, remission was obtained in 87.4% (76/87) and 69.2% (9/13) for CD and UC patients respectively. The median duration of MTX therapy was 40 months for CD and 15 months for UC. Occurrence of adverse events was the first reason for treatment discontinuation (39.4% of all cases). The rate of mucosal healing with MTX was 9.5% for CD and 25% for UC patients respectively. CONCLUSION: MTX therapy was effective for the induction and maintenance therapy in IBD patients, with only a modest mucosal healing ability.

[Doctor : « I hurt everywhere ¼]. / « Docteur, j'ai mal partout ¼.

Faced with diffuse pain, the doctor must evoke a wide range of pathologies. It is necessary to think about rare illnesses such as myopathy or vasculitis, but also more common illnesses such as fibromyalgia. Contrary to popular belief, it is difficult to give a diagnosis of fibromyalgia, on average 2 years after the onset of symptoms. This can be explained by heterogeneous complaints and the doctor delaying the diagnosis with unnecessary complimentary examinations.Patient education and physical activity are the most important steps of treatment. Few drugs have proven effective and their use is limited due to significant side effects. The evolution of fibromyalgia is chronic, with a mixed prognosis.

Face aux algies diffuses, le médecin doit évoquer un large éventail de pathologies. Il faut penser à la fois aux maladies rares comme les myopathies ou les vasculites, mais aussi aux maladies plus fréquentes comme la fibromyalgie. Contrairement aux idées reçues, le diagnostic de fibromyalgie est difficile à poser, en moyenne 2 ans après le début des symptômes. Ceci s'explique par des plaintes hétérogènes, mais aussi par le médecin lui-même qui retarde le diagnostic par des examens complémentaires inutiles. L'éducation du patient et l'activité physique sont les étapes les plus importantes de la prise en charge. Peu de médicaments ont prouvé leur efficacité et leur utilisation est limitée par d'importants effets secondaires. L'évolution de la fibromyalgie est chronique avec un pronostic plutôt mitigé.

The dermatologists' role in managing psoriatic arthritis: results of a Swiss Delphi exercise intended to improve collaboration with rheumatologists.

BACKGROUND: Psoriatic arthritis (PsA) substantially impacts the management of psoriatic disease. OBJECTIVE: This study aimed to generate an interdisciplinary national consensus on recommendations of how PsA should be managed. METHODS: Based on a systematic literature search, an interdisciplinary expert group identified important domains and went through 3 rounds of a Delphi exercise, followed by a nominal group discussion to generate specific recommendations. RESULTS: A strong consensus was reached on numerous central messages regarding the impact of PsA, screening procedures, organization of the interaction between dermatologists and rheumatologists, and treatment goals. CONCLUSION: These recommendations can serve as a template for similar initiatives in other countries. At the same time, they highlight the need to take into account the impact of the respective national health care system.

Tumor necrosis factor α inhibition in radiographic and nonradiographic axial spondyloarthritis: results from a large observational cohort.

OBJECTIVE: To evaluate the baseline characteristics of patients with radiographic axial spondyloarthritis (SpA; ankylosing spondylitis [AS]) and patients with nonradiographic axial SpA, to investigate determinants of anti-tumor necrosis factor (anti-TNF) agent prescription on the background of a nonrestrictive reimbursement policy, and to assess the response to TNF inhibition. METHODS: We compared the characteristics of radiographic axial SpA and nonradiographic axial SpA in 1,070 patients from the Swiss Clinical Quality Management (SCQM) Cohort who fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA. By taking advantage of the situation that patients who are eligible for anti-TNF treatment are preferentially enrolled in the SCQM Cohort for patients with AS/axial SpA, we explored parameters leading to the initiation of anti-TNF treatment in single and multiple regression models and assessed treatment responses. RESULTS: We confirmed a similar burden of disease (as determined by self-reported disease activity, impaired function, and quality of life) in patients with nonradiographic axial SpA (n = 232) and those with radiographic axial SpA (n = 838). Patients with radiographic axial SpA had higher median levels of acute-phase reactants and higher median AS Disease Activity Scores (ASDAS; 3.2 versus 3.0). Anti-TNF treatment was initiated in 363 patients with radiographic axial SpA and 102 patients with nonradiographic axial SpA, preferentially in those with sacroiliitis on magnetic resonance imaging, peripheral arthritis, a higher C-reactive protein (CRP) level, a higher ASDAS, and a higher Bath Ankylosing Spondylitis Disease Activity Index level. The ASAS criteria for 40% improvement responses at 1 year were higher in patients with radiographic axial SpA compared with those with nonradiographic axial SpA (48.1% versus 29.6%; odds ratio [OR] 2.2, 95% confidence interval [95% CI] 1.12-4.46, P = 0.02). The difference was smaller in the subgroups of patients with elevated baseline CRP levels (51.6% in patients with radiographic axial SpA versus 38.5% in those with nonradiographic axial SpA; OR 1.7, 95% CI 0.68-4.48, P = 0.29). CONCLUSION: The indications for treatment with anti-TNF agents were comparable for patients with radiographic axial SpA and those with nonradiographic axial SpA. With the exception of patients with elevated CRP levels at baseline, higher rates of response to TNF inhibition were achieved in the group of patients with radiographic axial SpA than in the group with nonradiographic axial SpA.

Morphometric vertebral assessments via the use of dual X-ray absorptiometry for the evaluation of radiographic damage in ankylosing spondylitis: a pilot study.

We performed a pilot study to compare vertebral fracture assessments (VFA) and lateral X-rays in terms of inter- and intraobserver reliability and degree of correlation for the detection of syndesmophytes in ankylosing spondylitis (AS). We recruited 19 patients with AS and recent lumbar or cervical lateral X-rays with at least one syndesmophyte. Each patient underwent dual-energy X-ray absorptiometry with measurement of bone mineral density and dorso-lumbar VFA. Intra- and interreader reliability for VFA and X-rays were measured using 2 independent, blinded observers and Cohen's kappa values. An adapted modified Stoke Ankylosing Spondylitis Spinal Score (amSASSS) was generated with each method, and these 2 values correlated. For X-rays, intraobserver and interobserver agreement were 94.3% (κ = 0.83) and 98.6% (κ = 0.96), respectively; for VFA, corresponding values were 92.8% (κ = 0.79) and 93.8% (κ = 0.82). Overall agreement between the 2 techniques was 88.6% (κ = 0.72). The Pearson correlation coefficient for the 2 methods was 0.95 for the modified Stoke Ankylosing Spondylitis Spinal Score . Per dual-energy X-ray absorptiometry-generated bone mineral density, >50% of patients were osteopenic and 10% osteoporotic. In terms of reproducibility and correlation with X-rays, performing a VFA appears to be a candidate for assessing radiographic damage in AS, thought further research is necessary to justify this indication.

[Imaging in low back pain: limits and reflexions]. / Place de l'imagerie dans la douleur lombaire: limites et réflexions.

Lumbar imaging is frequently requested in patients with low back pain for various reasons. However, the prevalence of severe lesions, including neoplastic, is only about 1%. Imaging in the absence of clinical suspicion performs poorly. Similarly, the imagery is no more likely to identify the anatomical structures that are the source of pain for patients with low back pain. Finally, the literature shows that the impact on treatment decisions and the effect on quality of life of patients cannot justify an indiscriminate use of these investigative techniques. Without questioning the value of imaging, the practitioner must keep in mind these limitations in order to optimize the use of this resource.

Long-lasting improvement of refractory antisynthetase syndrome with tocilizumab: a report of two cases.

No standardised and universal treatment is available for antisynthetase syndrome. In particular, there is an unmet need for a single efficient treatment acting on its various manifestations, including interstitial lung disease, myositis and polyarthritis.We describe the cases of two patients with multiple and severe manifestations, including joint, muscular and lung involvement, both refractory to various treatments, including rituximab, who demonstrated significant improvement of all their manifestations, including joint, muscular and lung diseases on tocilizumab. The response was also long-lasting, with both patients still being in full remission after >10 years of treatment.Our experience shows that interleukin-6 inhibition could be a very effective treatment option in antisynthetase syndrome, with efficacy on a wide spectrum of manifestations.

Serious infection risk of tofacitinib compared to biologics in patients with rheumatoid arthritis treated in routine clinical care.

Recently, serious infections related to the use of tofacitinib (TOF) for treatment of rheumatoid arthritis (RA) have raised considerable interest. This study aimed to compare the risk for serious infections in patients with RA upon receiving TOF versus biologic disease-modifying antirheumatic drugs (bDMARDs) by age at treatment initiation. We identified adult RA patients exposed to TOF or bDMARDs using data collected by the Swiss registry for inflammatory rheumatic diseases (SCQM) from 2015 to 2018. The event of interest was the first non-fatal serious infection (SI) during drug exposure. Missing or incomplete SI dates were imputed as either the lower (left) or upper (right) limit of the known occurrence interval. The ratio of SI hazards (HR) of TOF versus bDMARDs was estimated as a function of age using covariate-adjusted Cox regression applied to each type of imputed time-to-SI. A total of 1687 patients provided time at risk for a first SI during study participation and drug exposure for 2238 different treatment courses, 345 for TOF and 1893 for bDMARDs. We identified 44 (left imputation) or 43 (right imputation), respectively, first SIs (12/12 on TOF versus 32/31 on bDMARDs). Left and right imputation produced similar results. For patients aged ≥ 69 years, the treatment HR started to be increased (lower limit of 95% confidence intervals (LLCIs) > 1). By the age of 76, the difference between TOF and bDMARDs started to be clinically relevant (LLCIs > 1.25). For patients aged < 65 years, the data were insufficient to draw conclusions. Our results suggest that we should expect an increased risk for SIs in older patients treated with TOF compared to bDMARDs supporting a cautious use of TOF in these patients.