Long-Term Effectiveness of Baricitinib and Other b/tsDMARDs in Patients with Rheumatoid Arthritis with Early Low Disease Activity or Remission: 2-Year Data from the RA-BE-REAL Study
- Open Access
- 23.12.2025
- Original Research
Erschienen in:
Abstract
Key Summary Points
Why carry out this study? |
Recent evidence suggests that treatment strategies for rheumatoid arthritis (RA) should be based on early diagnosis and aim to achieve sustained remission. |
The ‘Window of opportunity’ describes the time when the benefits of early intervention with disease-modifying drugs is most likely to stop disease progression of RA. |
Delay in initiating treatment in newly diagnosed patients with RA is associated with joint damage, less drug-free remission, and poorer cost-effectiveness outcomes. |
What was learned from the study? |
In a real-world population, the achievement of early remission or LDA was associated with continued remission or LDA at 2 years as well as long-term improvement in pain, physical function, and quality of life. |
Real-world evidence offers practical insights that enhance clinical decision-making and complement randomized controlled trials. While observational studies may carry limitations, including potential selection bias, they provide valuable context grounded in everyday patient care. |
These findings support the importance of early achievement of the treat-to-target goal of remission or LDA in real-world clinical settings with baricitinib. |
Introduction
The current treat-to-target strategy for rheumatoid arthritis (RA) aims for sustained remission or at least low disease activity (LDA) through regular monitoring of disease activity and adaption of therapy if at least 50% reduction of clinical disease activity is not achieved within 3 months and remission or LDA is not reached within 6 months of therapy initiation [1]. Maintaining adherence and persistence to DMARD therapy is essential for achieving therapeutic benefits when aiming for disease remission or low disease activity [2]. Treating to achieve early remission or LDA may improve long-term functioning, quality of life, and structural outcomes [3‐5]. A meta-analysis by Yu and colleagues showed that predictors of remission included being male, higher education levels, and lower baseline disease activity [6]. Previous studies have demonstrated an association between high disease activity (HDA) and comorbidities, including major adverse cardiovascular events, venous thromboembolism, and some infections [7‐10]. Furthermore, a higher number of comorbidities has been shown to correlate with a poorer probability of achieving disease remission [11, 12]. Additionally, patients with persistent HDA have a two-fold higher mortality risk compared to patients with LDA [13]. Despite recommendations, the treat-to-target strategy appears to be under-implemented in real-world clinical practice [14] and the factors associated with the attainment of early remission or LDA are, as yet, not well understood.
Anzeige
Baricitinib is an oral, reversible, and selective inhibitor of Janus kinase (JAK)1 and JAK2 approved for the treatment of adults with moderate-to-severe active RA, moderate-to-severe atopic dermatitis, and severe alopecia areata, in Europe, Japan, and multiple other countries[15]. Several randomised, controlled trials have reported the efficacy and safety of baricitinib across different patient populations with RA, including naïve (RA-BEGIN), inadequate responders to methotrexate (RA-BEAM) and csDMARDs (RA-BUILD), as well as inadequate responders to bDMARDs (RA-BEACON) [16‐19]. To date, there are limited clinical-trial or real-world evidence data describing the factors associated with the achievement of early remission or LDA at 3 months in patients with RA.
RA-BE-REAL is a 3-year, multinational, prospective, observational study of adult patients with RA evaluating time to discontinuation of initial RA treatment. Here, we aim to report the early achievement of remission or LDA at 3–6 months and explore the long-term (2 years) outcomes of achieving early remission or LDA.
Methods
Study Design and Patient Population
RA-BE-REAL is an ongoing real-world observational study being conducted across five European countries (France, Germany, Italy, Spain, and the United Kingdom) as well as Australia, Canada, and Saudi Arabia. RA-BE-REAL commenced in October 2018, and completion is expected in October 2024. Patient enrolment for European countries was completed in March 2020, while enrolment is ongoing in other countries. This analysis includes patient data from European countries after 24 months of follow-up.
The RA-BE-REAL study design has been previously published [20]. Eligible patients were aged 18 years or older, met the criteria for RA according to their treating physician, and were prescribed baricitinib, any other tsDMARD, or bDMARD per local label requirements for the first time at any point in the treatment algorithm. Patients in cohort A initiated treatment with baricitinib (2 mg or 4 mg), while patients in cohort B initiated any biologic (b) disease-modifying anti-rheumatic drug (DMARD) or any other targeted synthetic (ts) DMARD. In both cohorts, the targeted DMARD could be used whatever the position in therapeutic lines, but patients had to be naïve to the study molecule.
Anzeige
Treatment initiation with baricitinib, any other tsDMARD, or any bDMARD, and treatment changes during the observation period, were solely at the discretion of the physician and the patient, in line with locally applicable guidelines and clinical routine. Data were collected at baseline (defined as initiation of treatment with baricitinib, any bDMARD, or any other tsDMARD) and at routine clinical care visits post-baseline at approximately 3, 6, 12, 18, 24, and 36 months. Eligible patients were aged 18 years or older, met the criteria for RA according to their treating physician, and were prescribed baricitinib, any other tsDMARD, or bDMARD per local label requirements for the first time at any point in the treatment algorithm.
Study Objectives and Endpoints
The primary objective of the RA-BE-REAL study was to assess the time to discontinuation of initial baricitinib, any other tsDMARD, or any bDMARD treatment for all causes (excluding sustained clinical response) over 24 months.
This analysis aims to report the proportion of patients achieving Clinical Disease Activity Index (CDAI) remission (defined as CDAI score ≤ 2.8) or LDA (defined as CDAI score of > 2.8 and ≤ 10) at 3 months and the long-term outcomes of achieving remission or LDA at 24 months. Clinical outcomes, including CDAI, pain visual analogue scale (VAS; 0–100 mm scale), the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L), were measured at 3 and 24 months.
Statistical Analyses
Effectiveness data at 3 and 24 months were presented descriptively. Logistic regression was used to determine the association between baseline characteristics and early achievement of remission or LDA at 3 months. The model's response outcome included patients who achieved remission or LDA at 3 months, which was the target outcome, as well as those who did not achieve remission or LDA at 3 months. The baseline characteristics serve as the independent variables in assessing the factors associated with the likelihood of early remission or LDA at 3 months. Logistic regression was also used to determine the association between early remission or LDA at 3 months and the achievement of long-term remission or LDA at 24 months. The model's response outcome included patients who achieved remission or LDA at both 3 months and 24 months, which was the target outcome, in addition to those who did not achieve remission and LDA at 3 and 24 months. The independent variable for assessing the likelihood of long-term remission or LDA at 24 months is the variable that contained the patients who achieved remission or LDA as a reference and those who did not achieve remission or LDA at 3 months. Missing data were not imputed; analyses were conducted using only complete observed cases.
Ethics
This study was conducted in accordance with Good Clinical Practice, the principles of the Declaration of Helsinki, and local laws and regulations in the five European countries. All patients provided written informed consent prior to entry to the study. Patients or the public were not involved in the design, conduct, reporting, or dissemination plans of our research.
Results
Baseline Characteristics of Patients Who Achieved or Did Not Achieve Early Remission or Low Disease Activity
At 3 months, 59.4% (N = 190) and 49.3% (N = 174) of patients in cohort A and cohort B, respectively, had achieved either remission or LDA at 3 months (Table 1). Mean age at baseline was 58.8 years (Standard deviation [SD] = 13.4) (cohort A) and 56.1 years (SD = 14.4) (cohort B) in those who achieved remission or LDA while the mean age for those who did not achieve remission or LDA was 59.6 years (SD = 13.0) and 57.4 years (SD = 13.0) for cohorts A and B, respectively. In cohort B, the duration of RA was numerically shorter among patients who achieved remission or LDA at 3 months, but the duration was numerically similar in cohort A, irrespective of having achieved early remission or LDA. In both cohorts, a numerically higher proportion of patients were naïve to b/tsDMARD amongst those who achieved remission or LDA at 3 months than those who did not achieve this target. A numerically higher proportion of patients who did not achieve remission or LDA at 3 months had previously been treated with more than two b/tsDMARDs. Mean baseline disease activity was numerically similar between patients who achieved or did not achieve remission or LDA at 3 months.
Table 1
Baseline demographics, treatment history, and clinical characteristics for patients who achieved or did not achieve CDAI remission or LDA at 3 months
Achieved remission or LDA | Did not achieve remission or LDA | |||
|---|---|---|---|---|
Cohort A n/N = 190/320 59.4% | Cohort B n/N = 174/353 49.3% | Cohort A n/N = 130/320 40.6% | Cohort B n/N = 179/353 50.7% | |
Patient demographics | ||||
Age, years, mean (SD) | 58.8 (13.4) | 56.1 (14.4) | 59.6 (13.0) | 57.4 (13.0) |
< 65 years | 127 (66.8) | 122 (70.1) | 81 (62.3) | 125 (69.8) |
≥ 65 years | 63 (33.2) | 52 (29.9) | 49 (37.7) | 54 (30.2) |
Female | 143 (75.3) | 124 (71.3) | 105 (80.8) | 146 (81.6) |
BMI (kg/m2), mean (SD) | 26.1 (5.1) | 26.2 (5.6) | 27.1 (5.3) | 27.6 (6.4) |
Smoking | ||||
Current | 41 (21.6) | 28 (16.1) | 26 (20.0) | 32 (17.9) |
Former | 34 (17.9) | 47 (27.0) | 32 (24.6) | 55 (30.7) |
Never or unknown | 115 (60.5) | 99 (56.9) | 72 (55.4) | 92 (51.4) |
RA treatment history | ||||
Family history of RA | 30 (15.8) | 23 (13.2) | 20 (15.4) | 40 (22.3) |
Duration of RA from diagnosis to enrolment, years, mean (SD) | 10.0 (9.1) | 7.4 (8.3) | 10.5 (9.5) | 9.8 (10.4) |
Prior RA treatment | ||||
b/tsDMARD-naïve | 109 (57.4) | 111 (63.8) | 39 (30.0) | 99 (55.3) |
Any bDMARD or tsDMARD | 81 (42.6) | 63 (36.2) | 91 (70.0) | 80 (44.7) |
TNFi | 57 (30.0) | 46 (26.4) | 63 (48.5) | 61 (34.1) |
Biologic (excl. TNFi) | 34 (17.9) | 28 (16.1) | 50 (38.5) | 40 (22.3) |
tsDMARD | 11 (5.8) | 12 (6.9) | 11 (8.5) | 12 (6.7) |
Number of previous b/tsDMARD treatments at any time before enrolment | ||||
1 b/tsDMARD | 24 (12.6) | 19 (10.9) | 18 (13.8) | 15 (8.4) |
2 b/tsDMARDs | 34 (17.9) | 23 (13.2) | 39 (30.0) | 31 (17.3) |
> 2 b/tsDMARDs | 23 (12.1) | 21 (12.1) | 34 (26.2) | 34 (19.0) |
Monotherapy | 85 (44.7) | 48 (27.6) | 63 (48.5) | 66 (36.9) |
Oral glucocorticoid treatment for RA at the time of enrolment | 84 (44.2) | 76 (43.7) | 69 (53.1) | 88 (49.2) |
Clinical characteristics | ||||
CDAI score, mean (SD) | 20.1 (10.1) | 19.2 (10.3) | 28.5 (12.1) | 27.2 (12.2) |
Pain VAS, mean (SD) | 52.5 (23.1) | 49.0 (23.1) | 65.4 (21.4) | 61.9 (22.7) |
HAQ-DI, mean (SD) | 1.1 (0.7) | 1.0 (0.7) | 1.7 (0.6) | 1.6 (0.6) |
EQ-5D-5L VAS, mean (SD) | 56.1 (21.3) | 56.6 (22.0) | 43.2 (23.1) | 48.6 (22.4) |
EQ-5D-5L utility, mean (SD) | 0.6 (0.2) | 0.6 (0.2) | 0.4 (0.2) | 0.5 (0.3) |
Effectiveness at 3 and 24 Months for Patients Achieving or Not Achieving Early Remission or Low Disease Activity
Amongst patients who achieved remission or LDA at 3 months, 82% and 75.7% of patients were still in remission or LDA in cohort A and cohort B, respectively, at 24 months (Table 2). Amongst patients who did not achieve remission or LDA at 3 months, 43.2% and 52.5% of patients achieved remission and LDA in cohort A and cohort B, respectively, at 24 months.
Table 2
Clinical outcomes at 3 and 24 months for patients who achieved or did not achieve CDAI Remission or LDA at 3 months
Achieved remission or LDA at 3 months | Did not achieve remission or LDA at 3 months | |||||||
|---|---|---|---|---|---|---|---|---|
Clinical outcomes at 3 months | Clinical outcomes at 24 months | Clinical outcomes at 3 months | Clinical outcomes at 24 months | |||||
Cohort A (N = 190) | Cohort B (N = 174) | Cohort A (N = 190) | Cohort B (N = 174) | Cohort A (N = 130) | Cohort B (N = 179) | Cohort A (N = 130) | Cohort B (N = 179) | |
CDAI score CFB | − 15.7 (10.1) | − 14.5 (10.4) | − 14.6 (10.9) | − 11.9 (12.2) | − 8.6 (12.5) | − 6.2 (12.4) | − 15.8 (15.4) | − 12.0 (12.7) |
Remission, n (%) | 67 (35.3) | 58 (33.3) | 42 (32.8) | 44 (37.0) | 0 (0.0) | 0 (0.0) | 6 (8.1) | 10 (8.2) |
LDA, n (%) | 123 (64.7) | 116 (66.7) | 63 (49.2) | 46 (38.7) | 0 (0.0) | 0 (0.0) | 26 (35.1) | 54 (44.3) |
Pain VAS | − 32.6 (24.7) | − 27.5 (26.2) | − 26.2 (28.8) | − 19.4 (30.6) | − 9.6 (27.2) | − 8.6 (25.9) | − 20.4 (31.3) | − 15.1 (26.5) |
HAQ-DI | − 0.4 (0.6) | − 0.4 (0.6) | − 0.4 (0.7) | − 0.3 (0.6) | − 0.2 (0.6) | − 0.1 (0.5) | − 0.3 (0.6) | − 0.2 (0.6) |
EQ-5D-5L VAS | 15.8 (28.3) | 13.2 (29.5) | 14.3 (28.0) | 11.6 (25.9) | 7.7 (28.7) | 4.1 (26.0) | 10.6 (28.3) | 9.2 (26.0) |
EQ-5D-5L utility | 0.2 (0.2) | 0.2 (0.2) | 0.1 (0.3) | 0.1 (0.3) | 0.1 (0.3) | 0.1 (0.2) | 0.1 (0.3) | 0.1 (0.3) |
At 3 months, patients achieving early remission or LDA in cohort A and B had a greater mean change from baseline in CDAI score than those who did not achieve remission or LDA. Irrespective of cohort, patients who achieved remission or LDA had a greater mean change from baseline improvement in Pain VAS, HAQ-DI, and EQ-5D-5L VAS, at both 3 and 24 months. Additionally, more patients receiving baricitinib achieved a ≥ 50% improvement in their CDAI by three months (n = 189, 59.1%), compared to those who received another b/tsDMARDs (n = 169, 47.9%) (Table 3). For both treatment cohorts, more patients achieved LDA/REM at 6 months where a ≥ 50% improvement in their CDAI had been seen at three months.
Table 3
Proportion of patients who achieved LDA or remission at 6 months by patients who achieved ≥ 50% CDAI improvement and who achieved < 50% CDAI improvement at their 3-month visit
Achieved ≥ 50% CDAI improvement | Achieved < 50% CDAI improvement | |||
|---|---|---|---|---|
Cohort A | Cohort B | Cohort A | Cohort B | |
n/N = 189/320 59.1% | N = 169/353 47.9% | N = 114/320 35.6% | N = 174/353 49.3% | |
Missing, n (%) | 58 (30.7) | 56 (33.1) | 38 (33.3) | 64 (36.8) |
LDA/remission at 6 months, n (%) | 103 (54.5) | 84 (49.7) | 30 (26.3) | 41 (23.6) |
Not in LDA/remission at 6 months, n (%) | 28 (14.8) | 29 (17.2) | 46 (40.4) | 69 (39.7) |
Anzeige
Factors Associated with the Achievement of Early Remission or Low Disease Activity at 3 Months
Patients treated with baricitinib (cohort A) were significantly more likely to achieve early remission or LDA at 3 months compared to those treated with a bDMARD or any other tsDMARD (cohort B). Patients naïve to previous b/tsDMARDs were more likely to achieve early remission or LDA compared to patients treated with two or more previous b/tsDMARD therapies (Table 4). Also, patients who underwent combination therapy with csDMARDs were more likely to achieve early remission or LDA at 3 months. Total low CDAI score and low EQ-5D-5L VAS at baseline were significantly associated with the achievement of remission or LDA at 3 months. The achievement of early remission or LDA at 3 months was associated with the achievement of remission or LDA at 24 months (odds ratio [95% confidence interval] 0.3 [0.2, 0.4], p < 0.001).
Table 4
Logistic model for the associating factors with early achievement of CDAI remission or LDA at 3 months
Parameter | Category | Estimate (SE) | Odds ratio (95% CI) | Chi-square | P value |
|---|---|---|---|---|---|
Intercept | 1.3 (0.4) | 10.3 | 0.001 | ||
Cohort | Cohort B (b/tsDMARD) vs. cohort A (baricitinib) | − 0.7 (0.2) | 0.5 (0.3, 0.7) | 15.5 | < 0.001 |
csDMARDs | Yes vs. No | 0.5 (0.2) | 1.7 (1.1, 2.7) | 5.5 | 0.020 |
Number of previous b/tsDMARD treatments | 1 vs. naïve | − 0.3 (0.3) | 0.7 (0.4, 1.3) | 1.3 | 0.247 |
2 vs. naïve | − 0.6 (0.2) | 0.6 (0.4, 0.9) | 5.2 | 0.022 | |
> 2 vs. naïve | − 1.0 (0.2) | 0.4 (0.2, 0.6) | 14.8 | < 0.001 | |
Total CDAI | − 0.1 (0.0) | 0.9 (0.9, 1.0) | 54.8 | < 0.001 | |
EQ-5D-5L VAS | 0.0 (0.0) | 1.0 (1.0, 1.0) | 8.3 | 0.004 |
Discussion
Early achievement of remission or LDA has been linked with long-term improvement in functioning, prevention of damage, and patient quality of life [3‐5]. In RA-BE-REAL, a high proportion of patients in both cohorts reached either remission or LDA following 3 months of RA treatment. Patients who achieved early remission or LDA had greater improvement in long-term pain and quality of life measures than patients who did not reach the treat-to-target goal of remission or LDA.
Almost 60% of patients treated with baricitinib achieved remission or LDA at 3 months. These findings are very similar to results from the randomised controlled trial, RA-BEAM, in which a high proportion (68%) of bDMARD-naïve patients treated with baricitinib achieved either remission or LDA, as measured by DAS28-CRP, at 3 months, although in RA-BE-REAL population in cohort A was mainly bDMARD-inadequate responders (bDMARD-IR) [21]. Results from this study are also in agreement with Japanese subpopulations from RA-BEGIN and RA-BEAM [22], and a multicenter study from 11 Italian centers with 56% of patients achieving LDA or remission (56%) at 3 months with baricitinib treatment [23]. Moreover, a study evaluating the real-world effectiveness and safety of tofacitinib and baricitinib in a small cohort of 294 patients with RA in clinical practice found that 81.2% of patients treated with baricitinib achieved CDAI/LDA at 24 weeks [24]. Real-world studies often report lower remission rates compared to randomized clinical trials due to various real-life factors such as comorbidities, socioeconomic status, variability in patient adherence, and treatment protocols [6]. In RA-BE-REAL, we demonstrate using logistic regression that treatment with baricitinib (cohort A) was identified as a baseline factor associated with the achievement of early remission or LDA. Additionally, we demonstrate that achievement of early remission or LDA was predictive of long-term achievement of remission or LDA at 24 months. Similarly, Aletaha et al. highlighted a significant link between disease activity in the first 3 months of treatment and long-term disease activity at 1 year [4].
Logistic regression analysis revealed that exposure to two or more previous b/tsDMARDs reduces the probability of achieving remission or LDA compared to patients who were naïve. Similar findings have been reported across baricitinib randomised controlled trials, RA-BEAM (bDMARD-naïve) and RA-BEACON (bDMARD-experienced) [21]. Although not powered for comparison or significance, we consistently observe a higher reduction in cohort A than cohort B, including change from baseline in CDAI, Pain VAS, and EQ-5D-5L VAS, in both early (3 M) and later (24 M) timepoint. Additionally, previous real-world evidence studies have demonstrated that patients naïve to bDMARDs and/or tsDMARDs have a better clinical response to baricitinib [23]. Using multivariate logistic regression analysis in a Japanese multicenter registry revealed that having no previous tsDMARD experience was independently associated with the achievement of EULAR LDA [25]. These findings highlight the need for patients to be treated with the most effective treatment as early as possible.
Anzeige
Irrespective of cohort, patients who achieved remission or LDA had a greater mean change from baseline improvement in pain VAS and HAQ-DI, at both 3 and 24 months, which are indicators of clinical and functional improvement [26]. Finally, we observed that HDA (CDAI) and low quality of life (EQ-5D-5L VAS) at baseline are negative predictors for achieving early remission or LDA. Acosta-Mérida et al. (2020) previously noted using multiple logistic regression analyses that male sex, diagnosis in the first year of symptoms and initial DAS28 are independent predictors for sustained remission [27]. Several previous studies demonstrated that male sex and a shorter duration of symptoms at baseline were independent predictors for sustained remission [27‐30]. In contrast, these factors were not significantly associated with the achievement of LDA or remission at 3 months amongst patients included in RA-BE-REAL.
Strengths
RA-BE-REAL is one of the first large-scale multinational studies generating real-world evidence on the use of baricitinib, bDMARDs, and other tsDMARDs in clinical practice. Due to stringent study inclusion criteria, randomised controlled trials do not fully reflect the treatment complexities and heterogeneous patient populations observed in real-world practice. This study included a large sample size of 1073 patients across multiple healthcare settings in Europe. In addition, ours is one of the first studies to examine the importance of early remission rather than focusing on baseline results.
Limitations
As an observational study, limitations include patient selection and participation bias and measurement error. Moreover, the observation window for the study was relatively small. Potential for bias, too, arises from the fact that choice of treatment with baricitinib, any bDMARD, or any other tsDMARD was based on the judgement of treating physicians. RA-BE-REAL is a real-world observational study, and by the very nature of such studies, randomization of certain variables is not possible. Finally, RA-BE-REAL is an ongoing trial with data cleaning still in progress; therefore sample size for this interim analysis was small and the potential for differences between interim and final data exists.
Conclusions
In a heterogeneous real-life population, a large proportion of patients with RA can achieve the treat-to-target goal at 3 months, as 59.4% and 49.3% of patients in cohort A and cohort B, respectively, achieved remission or LDA at 3 months. Early achievement of remission or LDA is associated with long-term sustained remission. This emphasizes the need for early diagnosis and intervention with the most efficacious agents. Achieving early remission or LDA was associated with beneficial long-term improvement in pain, physical function, and quality of life.
Anzeige
Acknowledgements
Eli Lilly and Company would like to thank the clinical trial participants and their caregivers, without whom this work would not be possible.
Medical Writing, Editorial, and Other Assistance
Medical writing assistance in the preparation of this article was provided by Nicola Roe, PhD, and Alan Ó Céilleachair, MSc (both employees of Eli Lilly and Company). Support for this assistance was funded by Eli Lilly and Company.
Declarations
Conflicts of interest
Rieke Alten has received consulting fees, payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events, and patents planned, issues, or pending from AbbVie, BMS, Celltrion, Galapagos, Janssen, Eli Lilly and Company, Novartis, Pfizer, Roche, UCB, and Viatris. Andrew Östör has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AbbVie, Pfizer, Eli Lilly and Company, Novartis, and Janssen. Christopher J. Edwards received honoraria from Eli Lilly and Company, received grant payments from AbbVie, Pfizer, Roche, Biogen, and Eli Lilly and Company, received personal fees from AbbVie, Astra-Zeneca, BMS, Celltrion, Fresenius, Galapagos, Gilead, GSK, Janssen, Roche, Pfizer, and Sanofi and travel and meeting payments from Eli Lilly and Company. Josef S. Smolen received grant/research support for his institution from: AbbVie, Astra-Zeneca, Eli Lilly and Company, Galapagos and Novartis; consultancy fees from: AbbVie, Ananda, Astro, BMS, Celltrion, Chugai, Eli Lilly and Company, Immunovant, Janssen, MSD, Novartis, Pfizer, Roche, R-Pharma, Samsung, Sanofi, and UCB. Ewa Haladyj and Khai Jing Ng are current employees and minor shareholders of Eli Lilly and Company. Yuko Kaneko received grants or speaking fees from AbbVie, Astellas, Ayumi, Bristol–Myers Squibb, Chugai, Eisai, Eli Lilly and company, Jansen, Kissei, Kirin, Novartis pharma, Pfizer, Sanofi, Takeda, Tanabe-Mitsubishi, and UCB. Samuel Ogwu was an employee of Eli Lilly and Company at the time of the study and is currently affiliated with Dublin Business School, Dublin, Ireland.
Ethical Approval
This study was conducted in accordance with Good Clinical Practice, the principles of the Declaration of Helsinki, and local laws and regulations in the five European countries. All patients provided written informed consent prior to entry to the study. Patients or the public were not involved in the design, conduct, reporting, or dissemination plans of our research.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
