Article Text

Early identification of axial psoriatic arthritis among patients with psoriasis: a prospective multicentre study
  1. Fabian Proft1,
  2. Susanne Lüders2,
  3. Theresa Hunter3,
  4. Gustavo Luna4,
  5. Valeria Rios Rodriguez5,
  6. Mikhail Protopopov1,
  7. Katharina Meier6,
  8. Georgios Kokolakis6,
  9. Kamran Ghoreschi6,
  10. Denis Poddubnyy7
  1. 1Department of Gastroenterology, Infectiology and Rheumatology, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, Berlin, Germany
  2. 2Department of Gastroenterology, Infectious Diseases and Rheumatology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Berlin, Germany
  3. 3Value Evidence and Outcomes, Eli Lilly and Company, Indianapolis, Indiana, USA
  4. 4Global Health Economics, Outcomes Research and Epidemiology, ICON plc, Stockholm, Sweden
  5. 5Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology (including Nutrition Medicine), Charite Universitatsmedizin Berlin, Berlin, Germany
  6. 6Department of Dermatology, Venereology and Allergology, Freie Universitat Berlin, Berlin, Germany
  7. 7Division of Gastroenterology, Infectious Diseases and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany
  1. Correspondence to Dr Theresa Hunter, Value Evidence and Outcomes, Eli Lilly and Company, Indianapolis, Indiana, USA; hunter_theresa_marie{at}lilly.com

Abstract

Objectives To evaluate a dermatologist-centred screening tool followed by a structured rheumatological examination including MRI of sacroiliac joints and spine for the recognition of psoriatic arthritis with axial involvement (axPsA).

Methods This was a prospective multicentre study. Adult patients with a confirmed diagnosis of psoriasis who had chronic back pain (≥3 months), onset <45 years and had not been treated with any biologic or targeted synthetic disease-modifying antirheumatic drug in the 12 weeks before screening were referred to a specialised rheumatology clinic. A rheumatological investigation including clinical, laboratory and genetic assessments as well as imaging with conventional radiography and MRI of sacroiliac joints and spine was performed. The primary outcome of the study was the proportion of patients diagnosed with axPsA among all referred patients with PsO.

Results Rheumatologists examined 100 patients of those who qualified for referral. 14 patients (including 3 with both axial and peripheral involvement) were diagnosed with axPsA and 5 were diagnosed with peripheral PsA solely. All patients diagnosed with axPsA had active inflammatory and/or structural (post)inflammatory changes in the sacroiliac joints and/or spine on imaging. In five patients, MRI changes indicative of axial involvement were found only in the spine. All but one patient with PsA (13/14 with axPsA and 5/5 with pPsA) fulfilled the Classification Criteria for Psoriatic Arthritis criteria for PsA. The Assessment of SpondyloArthritis International Society criteria for axSpA were fulfilled in 9 (64.3%) patients diagnosed with axPsA.

Conclusions Applying a dermatologist-centred screening tool may be useful for the early detection of axPsA in at-risk patients with psoriasis .

  • Magnetic Resonance Imaging
  • Epidemiology
  • Arthritis, Psoriatic

Data availability statement

Data are available on reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

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/.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

WHAT IS ALREADY KNOWN ON THIS TOPIC

  • Early diagnosis of psoriatic arthritis (PsA) (and psoriatic arthritis with axial involvement (axPsA) in particular) is essential and dermatologists are in a strategic position to screen at-risk patients with psoriasis before advanced structural damage of the joints and spine appears.

  • While different validated screening/referral tools focusing on peripheral manifestations of PsA exist, validated referral algorithms for axPsA are missing.

WHAT THIS STUDY ADDS

  • Our study revealed that application of a dermatologist-centred screening tool focusing on identifying signs of axial involvement among patients with psoriasis may be useful for the detection of PsA (and specifically axPsA) in these patients.

  • MRI of the spine in addition to MRI of sacroiliac joints is required to recognise patients presenting with spinal involvement only.

HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY

  • Our findings provide insights into the possibility of diagnosing axPsA early with the ultimate goal of improving the care and quality of life of patients living with this disease.

Introduction

Spondyloarthritis (SpA) encompasses a group of overlapping disorders, namely ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, undifferentiated SpA and non-radiographic axial SpA.1 Psoriatic arthritis (PsA) is a chronic, inflammatory musculoskeletal disease2–4 that affects up to 30% of patients with psoriasis5 6 and typically manifests as peripheral arthritis, enthesitis, dactylitis and skin and nail changes.7 8 Between 20% and 75% of patients with PsA have axial involvement (axPsA) and present with additional symptoms, such as back pain that might have inflammatory characteristics including morning stiffness.3 9

Back pain in patients with axPsA is caused by inflammation in sacroiliac joints and/or spine that over time might result into development of structural damage including radiographic sacroiliitis, syndesmophytes and ankylosis. AxPsA is associated with more severe disease and patients with axial involvement often experience worse pain, significantly impaired physical function and overall activity and reduced quality of life compared with patients without axial involvement.8 9

Because a delayed diagnosis of PsA (and axPsA in particular) may lead to irreversible joint and spinal damage and poor long-term outcomes,2 early diagnosis and treatment of patients with PsA is essential.3 5–7 However, PsA is a heterogeneous disease with a very variable clinical manifestation, which makes early identification very challenging.2 4

In the absence of reliable serological and/or imaging biomarkers for early PsA2 and an existing diagnostic delay, there is a need for screening tools for detection of early PsA. Skin lesions associated with psoriasis typically precede symptoms of PsA, which places dermatologists in a strategic position to screen at-risk patients before advanced structural damage of the joints and spine appears.3 However, despite awareness of the disease, prevalence of undiagnosed PsA among patients with psoriasis at risk remains high5 6 with up to one-third of patients with psoriasis who regularly attend dermatology clinics being undiagnosed for PsA.6

Moreover, while different validated screening/referral tools focusing on peripheral manifestations of PsA exist,10 validated referral algorithms for PsA with axial involvement (axPsA) are missing. To address this gap, we conducted a prospective, multicentre study in which we applied a dermatologist-centred, easy and not time-consuming screening tool followed by a structured rheumatological examination including MRI of sacroiliac joints and spine to identify patients with axPsA among patients with psoriasis attending dermatology clinics.

Methods

Study design and patient eligibility

This prospective, multicentre study was conducted in coordination with the Charité—Universitätsmedizin Berlin specialised rheumatology clinic and 14 dermatology sites in the area of Berlin, Germany between October 2019 and January 2020. Consecutive patients with psoriasis who consented to participating in the study were screened by their treating dermatologist for eligibility for referral to Charité specialised rheumatology clinic. Patients eligible for referral were adults (18 years or older) with a confirmed diagnosis of psoriasis who reported having chronic back (defined as back pain lasting ≥3 months) with onset prior to 45 years of age and who had not been treated with any biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) within 12 weeks prior to screening (online supplemental Annex 1).

Supplemental material

Patients who qualified for referral were contacted to schedule an appointment at the rheumatology clinic, where they confirmed their interest participating in the study and signed a second informed consent form. For all patients who attended the rheumatology clinic, a complete rheumatological investigation, including clinical, laboratory and genetic assessments namely the HLA-B27 as well as imaging with conventional radiography of sacroiliac joints and MRI of sacroiliac joints (short tau inversion recovery—STIR and T1-weighted sequences, semicoronal planes) and spine (STIR and T1-weighted sequences, sagittal planes) were performed. Plaque-type psoriasis severity was evaluated by Psoriasis Area and Severity Index.11

Images were evaluated by a panel consisting of at least two rheumatologists and a musculoskeletal radiologist; the presence or absence of radiographic sacroiliitis and the sacroiliitis grade on radiographs according to the modified New York (mNY) criteria12 and the presence or absence of active inflammatory and structural changes on MRI compatible with axial involvement was recorded by consensus. The diagnosis of axPsA (or pPsA) was performed clinically by the treating rheumatologist after performing the clinical examination of patients and receiving all the imaging, genetic and laboratory results.

Patient and public involvement

Patients and/or public were not involved in any steps of the design, conduct, analysis and results dissemination of this study.

Outcomes

The primary outcome of the study was the proportion of patients diagnosed with axPsA with or without peripheral involvement, among all referred psoriasis patients seen at the rheumatology clinic. Secondary outcomes included the proportion of patients diagnosed with peripheral PsA (pPsA) without axial involvement and the proportion of patients fulfilling the Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial spondyloarthritis (axSpA) and/or the Classification Criteria for Psoriatic Arthritis (CASPAR) for PsA criteria.

Statistical analysis

The proportion of patients with psoriasis diagnosed with axPsA or pPsA was calculated out of the total number of psoriasis patients referred and seen at the rheumatology clinic. The same approach was applied for the calculation of the proportion of patients fulfilling the ASAS classification criteria for axSpA and the CASPAR classification criteria for PsA.

Patient demographic, clinical, laboratory and imaging characteristics were tabulated and summarised by means, medians, SD, IQR (Q3–Q1), minimum and maximum for continuous variables and by number and percentages for categorical variables. All patients with psoriasis seen at the rheumatology clinic had fully completed screening questionnaires and underwent a complete rheumatological investigation. As only patients with PsO with fully completed screening questionnaires and complete data of the rheumatological assessment including imaging were included into this analysis, there were no missing data in the dataset.

Statistically significant differences between the psoriasis patients diagnosed with axPsA and patients with psoriasis diagnosed with neither axPsA nor pPsA were determined by using Mann-Whitney U test for continuous variables and χ² test for categorical variables. Significance tests were conducted at significance level α=0.05. All statistical analyses were conducted in SAS Studio V.9.4 (SAS Institute).

Results

Patient disposition and diagnosis of axPsA and pPsA

In total, 355 patients were screened at 14 dermatology sites, of whom 151 (42.5%) qualified for referral to Charité specialised rheumatology clinic. Rheumatologists ultimately examined 100 (28.2%) consecutively referred patients to reduce the risk of bias. The diagnosis of axPsA was made in 14 patients (14%), and 3 of these patients presented with both axial and peripheral involvement. The diagnosis of pPsA without axial involvement was made in five patients (5%). Finally, 81 (81%) patients were diagnosed with neither axPsA nor pPsA (figure 1).

Figure 1

Patient disposition, total number of patients screened, referred and seen by a rheumatologist. ASAS, Assessment of SpondyloArthritis International Society; axPsA, axial psoriatic arthritis; CASPAR, Classification Criteria for Psoriatic Arthritis; pPsA, peripheral psoriatic arthritis.

The ASAS classification criteria for axSpA were fulfilled in nine (64.3%) of the patients diagnosed with axPsA. All but one patient diagnosed with PsA (13/14 with axPsA and 5/5 with pPsA) fulfilled the CASPAR for PsA as illustrated in figure 1.

Demographic and clinical characteristics

Demographic and clinical characteristics of all patients are presented in table 1. The mean (SD) age was similar among patients diagnosed with axPsA (46.2 (13.6) years) and patients diagnosed with neither axPsA nor pPsA (45.7 (13.3) years), while patients diagnosed with pPsA were slightly younger (42.8 (9.0) years). Fifty-six per cent of all patients were female; the proportion of females was higher among patients diagnosed with axPsA (64.3%) and lower among patients diagnosed with pPsA (40.0%).

Table 1

Demographic and clinical characteristics of patients diagnosed with psoriasis with pPsA, axPsA and patients not diagnosed with PsA

Patients with axPsA had a lower mean (SD) psoriasis duration with 13.6 (9.2) years than those patients not diagnosed with PsA (20.3 (16.7) years); nevertheless, this difference did not reach statistical significance. Mean (SD) duration of back pain was lower as well among patient with axPsA (12.2 (15.2) years) compared with patients not diagnosed with PsA (18.6 (14.8) years). A larger proportion of patients with axPsA experienced inflammatory back pain compared with patients not diagnosed with PsA (57.1% vs 44.4%).

Compared with patients not diagnosed with PsA, patients with axPsA presented with a significantly higher disease activity as assessed by the Ankylosing Spondylitis Disease Activity (ASDAS) score; the mean (SD) ASDAS score was 2.9 (0.8) for patients with axPsA and 2.3 (0.7) for patients not diagnosed with PsA (p=0.017). Patients with axPsA also presented with higher disease activity as assessed by the Disease Activity in Psoriatic Arthritis (DAPSA) score; the mean (SD) DAPSA score was 17.5 (14.3) for patients with axPsA and 11.2 (7.4) for patients not diagnosed with PsA.

Laboratory and imaging characteristics

Laboratory and imaging characteristics of all patients are presented in table 2. A higher proportion of patients with axPsA had HLA-B27 positive compared with patients not diagnosed with PsA (28.6% vs 14.8%). Significant differences were noted on CRP (mg/L) levels among patients with axPsA and patients not diagnosed with PsA. The mean (SD) CRP level was 8.0 (10.8) in patients with axPsA and 2.5 (3.1) in patients not diagnosed with PsA (p=0.039). Moreover, patients with axPsA tended to present with elevated CRP, defined as CRP higher than 5 mg/L. 35.7% of patients with axPsA presented with elevated CRP compared with 13.6% of patients not diagnosed with PsA (p=0.041).

Table 2

Laboratory and imaging characteristics of patients diagnosed with psoriasis with pPsA, axPsA and patients not diagnosed with PsA

All patients diagnosed with axPsA had active inflammatory and/or structural (post)inflammatory changes in the sacroiliac joints and/or spine on imaging (table 2). In five (35.7%) patients, MRI changes indicative of axial involvement were found only in the spine (figure 2). Five (35.7%) patients with axPsA presented with radiographic sacroiliitis ≥2 unilaterally and four (28.6%) patients in this group presented with radiographic sacroiliitis fulfilling the mNY criteria.

Figure 2

Imaging features of axial involvement in patients with psoriasis diagnosed with axPsA. This Venn diagram represents imaging overlapping and non-overlapping imaging features in patients diagnosed with axPsA. There are five features spread across the image: radiographic sacroiliitis as per mNY criteria at the upper left corner, active inflammation on MRI of SIJ at the top, structural (post)inflammatory changes on MRI of SIJ at the upper right corner, active inflammation on MRI of spine at the bottom and structural (post)inflammatory changes on MRI of spine at the bottom left. For each, we see the number of patients who presented with a feature defined by a coloured lining and the patients that have overlapping features. The number of overlapping features in patients is also represented in colour. For example, we see that out of 13 patients with active inflammation in spine (MRI), 4 also had structural post inflammatory changes in spine (MRI) as coloured in red. Following, out of eight patients with structural changes SJI (MRI), three had structural post inflammatory changes in spine (MRI) and three radiographic sacroiliitis (mNY criteria) as represented in light red. mNY, modified New York; SIJ, sacroiliac joint.

None of the patients diagnosed with pPsA or not diagnosed with PsA had active inflammatory and/or structural (post)inflammatory changes in the sacroiliac joints and/or spine on imaging. Among patients not diagnosed with PsA, four (4.9%) presented with radiographic sacroiliitis ≥2 unilaterally; one of them (1.9%) had radiographic sacroiliitis fulfilling the mNY criteria. After MRI assessment, axPsA in these four patients could be excluded: three cases showed typical imaging patterns of osteitis condensans ilii (OCI) and one did not present any active inflammatory or structural changes in the SIJ.

Significant differences were noted in the proportion of patients that had radiographic sacroiliitis in this group compared with the axPsA group (table 2).

Previous and current treatments

A substantial proportion of patients with psoriasis seen at rheumatology were using non-steroidal anti-inflammatory drugs (NSAIDs) at screening (42%), although no significant differences were noted in NSAIDs use between patients diagnosed with axPsA and patients not diagnosed with PsA (57.1% vs 38.3%; p=0.185). Among all patients seen, a minority reported previous use of non-opioid and opioid analgesics (10% and 5%, respectively) (table 3).

Table 3

Previous and current treatments of patients diagnosed with psoriasis with pPsA, axPsA and patients not diagnosed with PsA

The most common systemic psoriasis therapy was methotrexate, used by 11% of patients in total. Common topical psoriasis therapies included steroids and vitamin D analogues, used by 78% and 52% of the patients, respectively (table 3).

Discussion

This prospective, multicentre study is, to our knowledge, one of the first studies that applied a dermatologist-centred screening/referral tool focusing on detecting axial involvement in patients with psoriasis. Furthermore, the current algorithm was useful for the detection of PsA in patients with psoriasis by applying a straightforward and simple criterion such as age (18 years of age or older), confirmed diagnosis of psoriasis, chronic back pain, defined as back pain lasting ≥3 months, having back pain onset prior to 45 years of age and not treated with biologics or targeted synthetic DMARD within the last 12 weeks.

In addition, in order to capture inflammatory/structural postinflammatory changes in the axial skeleton objectively, our study included MRI of sacroiliac joints and spine as a part of the rheumatological diagnostic approach for all patients. Our data provide further support for previous reports on the prevalence of PsA with and without axial involvement among patients with psoriasis and highlights the demographic and clinical characteristics of these patients with a special focus on imaging data.

We have found that 19% of patients seen by a rheumatologist in our study were diagnosed with PsA (5/100 with pPsA and 14/100 with axPsA), whereas 73.7% (14/19) of patients with PsA had axial involvement that is clearly related to the screening methodology focusing on axial symptoms. A study published in 2019 reported an overall prevalence of PsA among patients with psoriasis of 19.7%,13 whereas previous studies suggest that 25%–70% of patients diagnosed with PsA have axial involvement14

One study investigated presence of axial involvement in patients with PsA as defined by radiographic sacroiliitis ≥grade 2 unilaterally.15 In this study, 45% of patients presented with radiographic sacroiliitis ≥grade 2 unilaterally and 35% of patients fulfilled the mNY criteria for radiographic sacroiliitis.15 In our study, we have found that 28.6% and 35.7% of patients with axPsA presented with sacroiliitis ≥grade 2 unilaterally and as per the mNY criteria, respectively. However, we also investigated the overlap between radiographic and MRI findings and found that, while all four patients who fulfilled the mNY criteria for radiographic sacroiliitis also presented with active and/or structural (post)inflammatory changes in the sacroiliac joints on MRI, in five other patients, evidences of involvement of sacroiliac joints were only detected on MRI (figure 2). These findings highlight the importance of MRI in detecting axial involvement in patients with PsA in the absence of definite radiographic changes in the sacroiliac joints. Furthermore, even MRI of sacroiliac joints would have resulted in missing of patients with isolated spinal involvement, which represent a substantial proportion of patients with axial involvement in PsA. Additionally, also in the group not diagnosed with axPsA, suspicious findings by conventional radiography were observed in four patients, which were then judged as not compatible with axPsA but rather due to other causes such as OCI after MRI evaluation. This stresses again the rather low specificity of borderline abnormalities seen in conventional radiographs of the SIJs and highlights the importance of MRI assessments in patients with suspected inflammatory axial involvement.

Previous data reported suggest that males and females are, in general, equally affected by PsA.16 Among patients with axPsA, whereas Carvalho et al reported that males more commonly present with axial involvement,17 Nas et al have found a larger proportion of females with axial involvement compared with males (59.8% vs 40.2%).18

With regard to laboratory findings, a larger proportion of patients with axPsA in our study were HLA-B27 positive compared with patients not diagnosed with PsA (28.6% vs 14.8%) although the difference was not statistically significant.16 17 19 Interestingly, none of the patients diagnosed with PsA without axial involvement in our study were HLA-B27 positive. In addition, elevated C reactive protein (CRP) level has been considered strongly associated with incidence of PsA according to a recently published systematic literature review.20 While only one patient with pPsA in our study presented with elevated CRP (>5 mg/L), we have found that 35.7% of patients with axPsA had elevated CRP, and a significant difference was noted when compared with the group of patients not diagnosed with PsA. This finding is consistent with data reported by one study that demonstrated an association between elevated CRP and axial involvement in patients with PsA.21

A major strength of this study is its prospective design that allowed collection of high quality data since there were no missing data from records of patients who underwent a complete clinical and imaging investigation and included in this analysis. Furthermore, we collected data from patients attending 14 different dermatology sites in the Berlin area, which increased the representativeness of this population.

Our study has limitations. First, patients with PsO not fulfilling the referral strategy have not been evaluated; thus, the specificity of the strategy and the negative predictive value could not be evaluated. Furthermore, no validated and established PsA screening tool was part of this project and therefore no comparisons of the performances between our screening tool and already existing screening tools for PsA in general could be applied. In addition to that, our screening approached specifically focused on patients with chronic back pain that started before the age of 45 years and therefore patients with a later onset of their axial disease or those with isolated peripheral involvement of their PsA would have been missed. Further, imaging—representing at the same time one the major strength of the study—had a relatively high impact on the final judgement on the presence or absence of axial involvement. Finally, a relatively small number of patients diagnosed with axPsA introduces some uncertainty in the estimation of the effects in the given populations.

To conclude, our study revealed that application of a dermatologist-centred screening tool may be useful for the detection of PsA (and specifically axPsA) in patients with psoriasis. The tool is easy to apply and not time-consuming, which makes its application feasible in daily practice ideally in combination with a screening for peripheral disease. In addition, the study provided evidence for the important role of imaging (and specifically MRI) in diagnosing axPsA. These results provide valuable real-world insights into the possibility of diagnosing axPsA early with the ultimate goal of improving the care and quality of life of patients living with the disease.

Data availability statement

Data are available on reasonable request.

Ethics statements

Patient consent for publication

Ethics approval

This study involves human participants and was approved by Local Ethics Committee of Charité—Universitätsmedizin Berlin, protocol number 2018–7929 and was conducted according to the principles of the Declaration of Helsinki. Participants gave informed consent to participate in the study before taking part.

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

  • Handling editor Josef S Smolen

  • Twitter @ProftDr, @MProtopopov

  • Contributors All authors contributed to the study design, interpretation of results and development of this manuscript. FP is the guarantor for this study.

  • Funding This study was sponsored by Eli Lilly and Company.

  • Competing interests Fabian Proft reported an institutional research grant from Lilly for the present manuscript as well as other institutional grants from Novartis and UCB. He also reports personal fees for consulting and payment for lectures and similar events, support for attending meetings/travel, participation on Data Safety Board or Advisory from AMGEN, Abbvie, BMS, Celgene, Janssen, Novartis, UCB, MSD, Pfizer, Roche. In addition, he is a Member of ASAS and leader of Y-ASAS 2021-2023, member and SC of GRAPPA and Chair of Y-GRAPPA for 2021–2024, member of EMEUNET/EULAR, DGRh, DEGUM and Rheumazentrum Berlin member. He has also received study materials from Aidian Oy; Susanne Lüders has nothing to disclose; Theresa Hunter is an employee of Eli and Lilly; Gustavo Luna reported institutional payments to ICON plc which he was employee at the time of the study; Valeria Rios Rodriguez has nothing to disclose; Mikhail Protopopov reported fees for attending meetings by UCB and for his participation on Data Safety Monitoring Board from Novartis; Katharina Meyers reported payment for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from Abbvie, Amgen, Almirall, Biogen, BMS, Celgene, Janssen-Cilag, UCB Pharma, Leo Pharma, Novartis and support for attending meetings from Abbvie, Amgen, Almirall, Biogen, BMS, Celgene, Janssen-Cilag, and UCB Pharma, Novartis and Participation on a Data Safety Monitoring Board or Advisory Board from BMS and Amgen. Georgios Kokolakis reports support from Lilly and consulting fees from Bayer and payment honoraria, support for attending meetings from Abbvie, Abbot, Actelion Pharmaceuticals, Amgen, Basilea Pharmaceutical, Biogen IDEC, BI, BMS, Celgene, Hexal, Janssen-Cilag, Leo Pharma, Eli Lilly, MSD, Sharp and Dohme, Mylna, Novartis, Parexel, Pfizer, UCB. Also reported participation on Data Safety monitoring or Advisory Board from AbbVie, Abbott, Amgen, Bayer, BI, BMS, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Novartis and UCB. Kamran Ghoreschi reported consulting fees from Abbvie, BI, BMS, Eli Lilly, Janssen Ciag, LEO Pharma, Viatris, Novartis, Pfizer and UCB as well as payment and honoraria. Denis Poddubnyy reported institutional grants from Lilly for the present manuscript as well as other institutional research grants from Abbvie, Eli Lilly, MSD, Novartis and Pfizer in the past 36 months. He also reports personal fees for consulting and/or Advisory board participation from AbbVie, Biocad, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis and UCB. He also reports personal speaker fees from AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer and UCB.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.