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Abstract
Objectives To assess how biological disease-modifying antirheumatic drugs (bDMARDs), glucocorticoids and disease activity affect risk of Staphylococcus aureus bacteraemia (SAB) in patients with rheumatoid arthritis (RA).
Methods In a nationwide cohort of patients with RA from the DANBIO registry, we conducted a nested case–control study including first-time microbiologically verified SAB cases from 2010 to 2018 and incidence density matched controls (1:4 by sex, age). We interlinked Danish registries and identified antirheumatic treatments, RA-specific clinical characteristics, comorbidities and socioeconomic status. The relative risk of SAB was assessed by adjusted ORs with 95% CIs and number needed to harm (NNH) reflected the absolute risk.
Results Among 30 479 patients, we identified 180 SAB cases (incidence rate: 106.7/100 000 person-years) and matched 720 controls (57% women, median age 73 years, IQR: 65–80). Risk of SAB was increased in current (OR 1.8 (95% CI 1.1 to 3.2)) and former bDMARD users (OR 2.5 (95% CI 0.9 to 7.0)), and in current users of oral glucocorticoids ≤7.5 prednisolone-equivalent mg/day (OR 2.2 (95% CI 1.3 to 4.0) and >7.5 mg/day (OR 9.5 (95% CI 3.9 to 22.7)) (non-use as reference). ORs for moderate/high disease activity compared with remission were 1.6 (95% CI 0.8 to 3.3)/1.5 (95% CI 0.6 to 4.3). Risk was increased in patients with longstanding RA (>10 years vs ≤3 years, OR=2.4 (95% CI 1.1 to 5.3)). The NNH was 1172(95% CI 426 to 9374) for current use of bDMARDs and 110(95% CI 43 to 323) for glucocorticoids >7.5 mg/day.
Conclusion We identified a dose-dependent increased risk of SAB in patients with RA currently using oral glucocorticoids. Daily use of >7.5 mg appeared to be a clinically relevant risk factor, whereas the absolute risk was low for bDMARDs. No clear impact of disease activity was found.
- rheumatoid arthritis
- biological therapy
- glucocorticoids
- epidemiology
- antirheumatic agents
Data availability statement
No data are available. According to Danish legislation, none of the original data can be shared.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Staphylococcus aureus is a leading cause of bacteraemia (SAB) and patients with rheumatoid arthritis (RA) are at increased risk of this severe condition.
It remains unclear how treatment with biological disease-modifying antirheumatic drugs (bDMARDs), glucocorticoids, and RA disease activity affect SAB risk.
WHAT THIS STUDY ADDS
In this nationwide nested case–control study of patients with RA, we found a dose–response relationship between daily and cumulative dose of oral glucocorticoids and the relative risk of SAB.
Use of glucocorticoids >7.5 mg/day prednisolone was a clinically relevant risk factor for SAB, based on relatively low number needed to harm, whereas the absolute risk associated with use of bDMARDs was low.
No clear impact of disease activity was found.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
This study demonstrates that prednisolone-sparing treatment should be carefully considered when higher dose oral glucocorticoids is needed for disease control.
Introduction
Rheumatoid arthritis (RA) is an inflammatory joint disease treated with immunosuppressive agents such as biological disease-modifying antirheumatic drugs (bDMARDs) and glucocorticoids, especially when conventional synthetic DMARDs (csDMARDs) are insufficient or not tolerated.1 2 Staphylococcus aureus is a leading cause of bacteraemia with ≈20% mortality and ≈30% risk of septic metastases causing secondary infections, such as endocarditis, osteomyelitis and joint infections.3–5 Risk factors include high age, male sex, comorbidities, implanted devices, surgical procedures and intravenous catheters.6 7
We have previously demonstrated an approximately doubled risk of S. aureus bacteraemia in Danish patients with RA compared with the general population and an up to fivefold increased risk for patients with RA with orthopaedic implants.8 However, it remains unknown how antirheumatic treatments and disease activity affect the risk, with existing studies being few and contradictory.9 10 One study found neither bDMARDs nor glucocorticoids to be associated with an increased risk in patients with RA, whereas another concluded that oral glucocorticoids increased the risk of S. aureus bacteraemia in the general population and in patients with various rheumatic diseases including RA.9 10 These studies were hampered by lacking information on RA-specific clinical characteristics, such as disease activity and severity, which are associated with both general infection risk and the choice of antirheumatic treatment.11 12 Thus, the impact of antirhematic treatments on the risk of S. aureus bacteraemia may have been confounded by indication.
In this nationwide, nested case–control study of patients with RA, we linked data from a prospective RA cohort in the clinical DANBIO registry to virtually complete registries of microbiologically verified S. aureus bacteraemia cases, vital status, prescriptions, hospital contacts and educational level. We aimed to investigate the impact of bDMARDs, glucocorticoids and disease activity on the risk of S. aureus bacteraemia.
Methods
Data sources
We identified patients with RA in the nationwide Danish rheumatological clinical database DANBIO.13 14 The validity of the RA diagnosis (positive predictive value ≈95%) and coverage of patients with RA (completeness ≈90% compared with the Danish National Patient Registry, DNPR) in DANBIO are high.14
We enriched DANBIO data with data from other national registries by interlinkage on the individual level using the unique personal identification number issued at birth or immigration.15 First-time cases of microbiologically verified S. aureus bacteraemia were retrieved in the Danish National S. aureus Bacteraemia Database (linked to personal identification numbers since 1992, completeness 94%–97%).16 17 Through the Civil Registration System, we determined vital status.15 In addition, we linked to the following virtually complete registries: the Population’s Education Registry for highest attained educational level as a proxy for socioeconomic status18–20; the DNPR for history of comorbidities, surgeries/procedures and hospital contacts21; and the Register of Medicinal Products Statistics (hereafter ‘the prescription registry’) regarding redeemed prescriptions for glucocorticoids and glucose-lowering medication (for the identification of diabetes mellitus).22 Information retrieved included anatomical therapeutical code, dose, formulation, package size and number of packages collected.22
Study population and nested case–control design
The DANBIO cohort consisted of adult (≥18 years) patients with RA without prior S. aureus bacteraemia, who were alive on 1 January 2010. Entry date was defined as the latest date of either RA diagnosis or first registered contact in DANBIO (online supplemental table S1) before 31 December 2018. We identified patients with a first occurrence of S. aureus bacteraemia (=case index event) between 1 January 2010 and 31 December 2018 (=study period).
Supplemental material
For the nested case–control study, we matched four controls per case by sex and age (1-year intervals) at the date of the case index event (=index date). Controls had to be alive at the index date and still at risk of a first-time S. aureus bacteraemia, and one patient could serve as control for several cases (incidence density matching).23
Main exposures
The exposures of main interest were predefined and included treatment with bDMARDs and glucocorticoids as well as RA disease activity.24
Users of bDMARDs had received any bDMARD (according to DANBIO) 0–24 months prior to the index date, as opposed to non-users. We subcategorised users according to most recent bDMARD use into either current (0–3 months prior to the index date, 0–12 months for rituximab) or former users (>3 months prior to index date, >12 months for rituximab). We further grouped current use by mode of action into tumour necrosis factor inhibitors (TNFi) and others (non-TNFi). Targeted synthetic DMARDs were rarely used (≤3 users among both cases and controls) and were not included.
For glucocorticoids, we identified oral users based on prescriptions, and parenteral users either by prescriptions or by glucocorticoid injections registered in DANBIO (online supplemental table S1). We defined users (including current and former users) and non-users as described above for bDMARDs. Current oral use was subcategorised according to daily and cumulative prednisolone-equivalent dose, respectively. Daily dose was either the dose at the index date in DANBIO or was estimated from the latest prescription before the index date, in categories of low (≤7.5 mg) or higher dose (>7.5 mg).25 26 Prescribed dose 0–6 months before the index date was summed up and categorised as ≤1000 mg, 1001–1500 mg or >1500 mg (online supplemental table S1).
Disease activity was estimated by the most recent Clinical Disease Activity Index (CDAI) score in DANBIO before index date and categorised as remission, low, moderate or high.27
Other covariates
Based on the literature, comorbidities potentially influencing S. aureus bacteraemia risk were defined a priori and identified in DNPR and the prescription registry (online supplemental table S1).6 7 28 We further identified all surgical procedures performed 0–30 days before the index date.
In DANBIO, we identified body mass index, smoking status and RA-specific clinical characteristics, including disease duration, serostatus, functional status, erosive status and treatment with csDMARDs (categorised as non-user, user, former user and current user as described above, with current users subcategorised into monotherapy and csDMARD combination therapy) (online supplemental table S1).29
Statistics
The incidence rate (IR) of S. aureus bacteraemia was calculated by dividing the number of S. aureus bacteraemia cases with the total number of person-years of follow-up in the DANBIO cohort in the study period, that is, whichever came last of entry date or 1 January 2010 and until first-time S. aureus bacteraemia, death, or 31 December 2018, whichever came first.
We characterised cases and controls at the index date with respect to for example, sex, age, RA treatment, disease activity, comorbidities and the fraction of cases caused by methicillin-resistant S. aureus (MRSA). The relative risk of S. aureus bacteraemia was assessed by adjusted ORs with 95% CIs computed by multivariate conditional logistic regression analyses, comparing cases with controls. When using incidence density matching, ORs may be considered unbiased estimates of IR ratios.30
We estimated ORs of S. aureus bacteraemia for oral glucocorticoids and bDMARDs stratified according to exposure definitions described above (see the Main exposures section) with non-users as the reference group. Similarly, we estimated ORs for disease activity with remission as reference. OR estimates for the main exposures were presented both as adjusted for age and sex and fully adjusted for all predefined potential confounders. We did not adjust for comorbidities affecting few patients (n≤3 for both cases and controls). For comparisons including strata with≤10 patients, we only presented age and sex adjusted ORs. Likewise, we investigated how the risk was associated with seropositive RA, longstanding RA (>10 years), and poor functional status, by estimating fully adjusted ORs (online supplemental table S1).
We calculated the estimated number of persons needed to be exposed per year for one extra case to occur (the number needed to harm, NNH) and the number of excess cases of S. aureus bacteraemia per 10 000 exposed per year for treatment exposures if both the fully adjusted OR and the lower confidence limit were above one. NNH was the inverse of excess cases, which was calculated based on the fully adjusted ORs and the IR in the cohort ((IR*OR)-IR). Confidence limits were calculated likewise using the 95% CIs to the ORs.31
We tested for interactions between current use of oral glucocorticoids and bDMARDs, and with either of these and sex, age and orthopaedic implants at index date. Also, we tested for multicollinearity by the variance inflation factor. All analyses were performed using SAS V.9.4.
Sensitivity analyses
We investigated the risk of S. aureus bacteraemia associated with disease activity in the subgroup of patients with a recent CDAI registration (0–6 months before the index date, both cases and controls) using multivariate ordinary logistic regression. Similarly, we explored the impact of persistent remission/low disease activity, moderate/high disease activity and fluctuating disease activity on the risk of S. aureus bacteraemia, in the subset of patients with ≥3 CDAI registrations 0–3 years before the index date. Furthermore, we explored the impact of treatment exposures on the risk of non-hospital acquired S. aureus bacteraemia, defined as cases who were either not hospitalised at the index date or with index-date less than 2 days after hospitalisation.
Missing data
Missing values of CDAI, educational level, Health Assessment Questionnaire (HAQ), serostatus, erosive status, body mass index and smoking status were imputed by multiple imputation by chained equation (100 dataset) with all the main analysis variables, the matching variables and the outcome variable included in the model.32
Patient and public involvement
We included a patient research partner in the hypotheses generating phase, which led to the inclusion of RA disease duration as an exposure.
Results
Characteristics of the DANBIO cohort
The cohort comprised 30 479 patients with RA contributing 168 729 person-years of follow-up. We observed 180 cases of first-time S. aureus bacteraemia corresponding an IR of 106.7/100 000 person-years.
For the nested case–control study, we included the 180 cases of S. aureus bacteraemia and identified 720 controls matched by age and sex. Patients with S. aureus bacteraemia were mainly women (57%) aged median 73 years (IQR 65–80). At index date, more cases had seropositive RA (76% vs 66% of controls), erosive disease (48% vs 39%), CDAI ‘moderate’ (29% vs 16%) or ‘high’ disease activity (10% vs 7%), HAQ score indicating ‘severe to very severe disability’ (28% vs 10%) and longer RA duration (years since diagnosis median 13.0 (IQR 6.2–21.4) vs 7.8 (IQR 3.5–14.4) for controls) (table 1). Furthermore, orthopaedic implants were more common among cases (53% vs 34%). HIV and history of solid-organ transplantation were rare. Cases often had recent surgery (38% vs 5%) (table 1). Previous comorbidities or recent surgery were present in 87% (n=157) of cases and 64% (n=458) of controls.
Characteristics of Danish patients with rheumatoid arthritis (RA) and Staphylococcus aureus bacteraemia (cases) from 2010 to 2018 and matched controls
Antirheumatic treatment and risk of Staphylococcus aureus bacteraemia in Danish rheumatoid arthritis patients from 2010 to 2018. a Age, sex, diabetes mellitus, cancer, chronic heart failure, chronic dialysis treatment, chronic obstructive pulmonary disease, orthopaedic implant, vascular prosthesis, pacemaker or other device, recent surgery, disease duration, years since entry, csDMARD use, treatments in other panels of the figure, with imputed data: disease activity, highest attained educational level, serostatus, erosive status, functional status, body mass index and smoking status. bDMARD, biological disease-modifying antirheumatic drug; csDMARD, conventional synthetic DMARDs; NA, not applicable; TNFi, tumour necrosis factor inhibitors.
Use of bDMARDs, glucocorticoids and risk of S. aureus bacteraemia
Use of bDMARDs 0–2 years before the index date was more frequent among cases compared with controls (38% vs 23%) (figure 1). Most were current users at the index date, however, more cases than controls had stopped treatment and former users constituted 20% of users (14/69) among cases vs 11% (18/162) for controls. In the fully adjusted analysis, current use of bDMARDs was associated with increased risk of S. aureus bacteraemia compared with non-use (OR 1.8 (95% CI 1.1 to 3.2)). Former users were also at increased risk, although the CI was wide and included one (OR 2.5 (0.9 to 7.0)). The risk did not vary substantially by mode of action (figure 1).
Current use of oral glucocorticoids was more frequent in cases compared with controls (41% vs 19%) and, in the fully adjusted analysis, OR for current users compared with non-users was 3.2 (95% CI 1.9 to 5.3) (figure 1). Most current users of glucocorticoids received doses ≤7.5 mg prednisolone per day. Higher dose (>7.5 mg/day) was more common for cases compared with controls and fully adjusted ORs increased in a dose-dependent manner from 2.2 (95% CI 1.3 to 4.0) for ≤7.5 mg/day to 9.5 (95% CI 3.9 to 22.7) for >7.5 mg/day. Similarly, for cumulative dose, from 2.0 (95% CI 1.1 to 3.8) for ≤1000 mg to 7.5 (95% CI 3.1 to 18.4) for >1500 mg. (figure 1).
Parenteral glucocorticoids were used infrequently and with similar frequency among cases and controls with no clear sign of increased risk in the adjusted analysis (figure 1).
The NNH associated with current use of >7.5 mg/day oral glucocorticoids was 110 (95% CI 43 to 323) and the number of excess cases/10 000 patients/year was 91 (95% CI 31 to 231) (table 2). The NNH estimates for current bDMARD use were approximately ten times higher than those for higher dose oral glucocorticoids.
Number needed to harm and excess cases of Staphylococcus aureus bacteraemia associated with drug exposures
Disease activity and risk of S. aureus bacteraemia
In the analysis adjusted for sex and age, high and moderate disease activity were associated with increased risk when compared with remission, however, OR estimates decreased in the fully adjusted analysis and CIs included one (table 3).
Risk of Staphylococcus aureus bacteraemia associated with disease activity in Danish patients with rheumatoid arthritis from 2010 to 2018
Other RA-specific clinical characteristics and risk of S. aureus bacteraemia
Patients with longstanding RA (>10 years) were at increased risk compared with those with early RA (≤3 years, OR 2.4 (95% CI 1.1 to 5.3). Erosive disease, poor functional status and seropositive RA appeared to be associated with increased risk, but CIs were wide and included one (table 4).
Risk of Staphylococcus aureus bacteraemia associated with rheumatoid arthritis (RA) characteristics
Model control and sensitivity analyses
The p value for the interaction term between sex and bDMARD use was 0.0110, however, in stratified analysis, adjusted ORs for current users versus non-users (men and women, respectively) were almost identical (online supplemental table S2). Former users differed but strata were too small for adjusted analysis. We found no sign of multicollinearity between covariates as assessed by estimated variance inflation factors.
The analysis of risk associated with disease activity restricted to patients with a recent registration of CDAI (0–6 months before index event) resulted in similar estimates to the main model, although high disease activity was rare and CIs were wide (online supplemental table S3). The OR estimates were slightly higher when comparing persistent moderate/high (OR 3.0 (95% CI 1.0 to 9.1)) and fluctuating disease activity (OR 1.4 (95% CI 0.8 to 2.6)) with persistent remission/low disease activity, however, the CIs for the fully adjusted OR estimates included one (online supplemental table S4).
The association between antirheumatic treatments and risk of non-hospital-acquired S. aureus bacteraemia (n=146 of 180=81%) was comparable to the main model (online supplemental table S5).
Discussion
In this nationwide study of patients with RA, current use of oral glucocorticoids in doses higher than 7.5 mg/day resulted in a 9.5-fold higher risk of S. aureus bacteraemia, even after adjusting for potential confounders including disease activity. Use of bDMARDs was associated with a doubled relative risk, however, the absolute risk was low, based on the NNH. Risk was increased in patients with longstanding RA, whereas no clear impact of disease activity was found.
We have previously reported increased incidence of S. aureus bacteraemia in patients with RA compared with the general population with the highest absolute risk in men >70 years of age and the highest relative risk among women aged <60 years.33 Risk factors for S. aureus bacteraemia in patients with RA have been sparsely studied.9 10 The apparent negative impact of oral glucocorticoid use reported in this study was strengthened by the dose–response relationship and by the fact that both cumulative dose in the preceding 6 months and the current daily dose increased the risk of S. aureus bacteraemia. Our results contradict a previous study finding no such association.9 However, patients with RA with non-S. aureus-related hospital admissions served as controls, which could have biased the impact of treatment towards no association. Another study reported an OR of 2.1 (95% CI 1.4 to 3.2) among patients with rheumatic diseases who currently used oral glucocorticoids, which is somewhat lower than ours.10 Possible explanations include the pooling of different rheumatic diseases in that study and lack of adjustment for concomitant antirheumatic treatments, disease activity and severity.
In contrast to previous findings, we identified an increased risk associated with current use of bDMARDs as compared with non-use in the preceding 2 years.9 However, former bDMARD use was associated with a similarly increased risk (although the CI included one). This finding may appear unexpected, but likely reflects that individuals susceptible to infections are more prone to terminate bDMARD treatment due to infectious or other adverse events, leaving them with insufficiently controlled disease activity and probably higher dosages of glucocorticoids.34
Our findings of an increased risk associated with longstanding RA and the overall pattern of a slightly increased risk associated with moderate/high disease activity, low functional status, erosive disease and seropositivity are new, although previous studies have demonstrated associations between low functional status, high disease activity and infections in general.12 35
Cases of S. aureus bacteraemia acquired during hospitalisation are often associated with surgical procedures or intravenous catheters, thus inherent risk factors might be less influential in hospital-acquired S. aureus bacteraemia.36 We found that the relative risk estimates of antirheumatic treatments were similar when analysing all S. aureus bacteraemia cases (ie, looking at hospital and non-hospital acquired cases together, main results), and when analysing non-hospital-acquired S. aureus bacteraemia cases separately (sensitivity analysis). This supports that the associations observed in our main results were not mediated by the cases acquired during hospitalisation.
This case–control study nested in a well-defined contemporary cohort of patients with RA allowed us to explore how S. aureus bacteraemia risk was associated with time-varying factors such as antirheumatic treatment and disease activity. Strengths include access to and linking at the individual level of (1) prospectively collected information regarding antirheumatic treatments (including glucocorticoids) and disease activity, (2) microbiologically ascertained cases of S. aureus bacteraemia with high completeness and validity, and (3) other virtually complete national registries. Discrepancies between actual drug use and drugs listed in electronic records challenge assessment of drug exposures.37 In this study, we combined information from prescriptions and DANBIO registrations to better capture users and the daily doses.
Limitations include the lack of power when estimating the impact of disease activity on the risk of S. aureus bacteraemia. Furthermore, median time elapsed since latest CDAI was 5 months, which could have caused an underestimation of the risk associated with higher disease activity and overestimation of risk associated with treatment. Reassuringly, we arrived at similar/marginally higher estimates both in the sensitivity analysis restricted to patients with a recent single registration of CDAI and in the analysis of persistent moderate/high disease activity restricted to patients with repetitive measurements. Similarly, functional status (HAQ) and erosive status may have changed in the time span from registration until the index date, however most will likely be unchanged, since median time elapsed since registrations were 4 months and 1 year, respectively. Furthermore, we may have underestimated risk associated with current use of antirheumatic treatments, since most current users had been using the drug for >3 months, which may have introduced a healthy user bias.38 39 However, the study was not powered to stratify according to new and continuing use. Patients with S. aureus bacteraemia prior to 1992 may have been included in the study, however, we expect only few such patients because of the long time span combined with the high age and high mortality of most patients with this infection.40 Few patients had MRSA bacteraemia, and the results may not be generalisable to populations with high MRSA prevalence. We observed that cases and controls differed in several aspects, and residual confounding caused by unmeasured differences may occur. Also, as in any study based on real-world data collected for administrative and clinical use, misclassification bias cannot be ruled out.
In conclusion, oral glucocorticoid use increased the risk of S. aureus bacteraemia in a dose-dependent manner in patients with RA. Especially daily use of >7.5 mg seemed to be a clinically relevant risk factor, whereas the absolute risk for bDMARD users appeared low. No clear impact of disease activity was found. Our findings demonstrate that prednisolone-sparing treatment should be carefully considered when higher dose oral glucocorticoid is needed for disease control.
Data availability statement
No data are available. According to Danish legislation, none of the original data can be shared.
Ethics statements
Patient consent for publication
Ethics approval
The study was registered and approved by the Capital Region of Denmark (approval number RH-2015-209), ensuring that data were handled in accordance to the General Data Protection Regulation (EU) 2016/679. Data from DANBIO were obtained through the Danish Rheumatologic Quality Registry (DRQ). Personal information was pseudonymised. No ethical approval is needed for register-based studies in Denmark.
Acknowledgments
We wish to thank patient research partner Pia Lüchau Pedersen for her assistance; Kristina Laugesen, MD, PhD, for scientific discussions on calculating estimated daily dose of oral glucocorticoids; statisticians Thomas Bøjer Rasmussen and Trine Frøslev for guidance; and we thank Gigtforeningen and Beckett-Fonden for their financial support for the study.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
BG and MLH are joint last authors.
Contributors SSD had full access to all data in the study and take responsibility for the accuracy of the data analysis and for the overall content as the guarantor. Study concept and design: SSD, MLH, BG, MN and CT-P. Analysis and interpretation of data: all authors. Drafting of the manuscript: SSD. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: SSD and FM.
Funding This study was supported by The Danish Rheumatism Association (grant numbers R163-A5715 and R188-A6548) and Beckett-Fonden (reference number 19-2-5090).
Competing interests SSD has received grants related to the submitted work from The Danish Rheumatism Association and Beckett-fonden. FM, MN, LBO and AP reports no disclosures. All outside the submitted work: TB reports grants from Novo Nordisk Foundation, Simonsen Foundation, Lundbeck Foundation, Kai Hansen Foundation, Erik and Susanna Olesen’s Charitable Fund; grants and personal fees from GSK, Pfizer, Gilead; and personal fees from Boehringer Ingelheim, MSD, Astra Zeneca, Janssen, Pentabase ApS; CT-P reports grants from Novo Nordisk and Bayer; BG reports grants from Pfizer, BMS, Sandoz, and chairs the steering committee of the Danish Rheumatology Quality Registry (DANBIO), which receives public funding from the hospital owners and funding from pharmaceutical companies, and; and Merete Hetland reports grants from Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis; co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondylarthritis based on secondary data and is partly funded by Novartis.
Provenance and peer review Not commissioned; externally peer reviewed.
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