Challenges and opportunities in access to care for systemic lupus erythematosus patients across Europe and worldwide

Abstract

SLE presents significant challenges for patients and health-care professionals (HCPs), both across Europe and worldwide. Improving health-care outcomes for patients with SLE requires a comprehensive understanding of patient disease pathways. In particular, the geographical distance between SLE patients and specialized care centres, combined with the scarcity of rheumatologists, exacerbates delays in diagnosis and management. Also, the initial SLE symptoms can often be non-specific, and providing guidelines for primary HCPs and other non-specialists is extremely important. Improvement in access to treatment is also important, with several recently approved therapies for SLE not being available in several European countries and many low- and middle-income countries (LMICs). Furthermore, in the LMICs in which these treatments are available, they are not always covered by the health-care system, making their access almost impossible for those of lower socio-economic status. A number of provisions are already in place within the European Union, to improve access to care for patients with rare and complex diseases, including those with SLE. In particular, European Reference Networks (ERNs), such the ERN for Autoimmune Diseases ReCONNET, are virtual networks involving HCPs across Europe with the aim of improving the care of patients with rare and complex diseases that require highly specialized treatment and a concentration of knowledge and resources. In addition, lupus patient organizations such as Lupus Europe play a crucial role in raising awareness of SLE and advocating for improved access to care. Together, we can work towards a future where all people living with lupus receive the comprehensive and timely care they deserve.

Introduction

SLE is a complex autoimmune disease with systemic manifestations that presents significant challenges for patients and health-care professionals (HCPs) in Europe and worldwide [1]. Despite its typical inclusion in the spectrum of rare diseases, SLE affects ∼3.44 million individuals worldwide [2], often requiring specialized care far from where the patients live. This, combined with a scarcity of rheumatologists, who play a vital role in the diagnosis and treatment of SLE, exacerbates the issues patients with SLE can face, particularly in rural or isolated areas. As a result, patients often suffer significant delays in diagnosis [3], increasing their burden of disease and the risk of organ damage. These difficulties are even more pronounced in low- and middle-income countries (LMICs), where limited health infrastructure and resources can further restrict access to specialist care [4, 5]. Many SLE patients in these regions lack access to essential diagnostic tests and therapies, particularly the latest biologics. Despite these challenges, there are opportunities for improvement. Advances in telemedicine and digital health technologies offer promising solutions for overcoming geographical barriers and improving access to care [6]. Collaborative efforts to train HCPs in resource-constrained environments can also improve the recognition and management of SLE [7]. Finally, European Reference Networks (ERNs), such as the European Reference Network for Autoimmune Diseases ReCONNET [8], enable collaboration with the aim of improving the overall quality of care across Europe. In this manuscript, we explore the complexities of access to care for patients with SLE, discussing the barriers they and HCPs face, and potential solutions for improving health-care outcomes for patients with SLE on a global scale. A transcript of the virtual roundtable video can be found in Supplementary Data S1, available at Rheumatology online.

Mapping SLE patient pathways

Improving health-care outcomes for SLE requires a comprehensive understanding of patient pathways. The concept of a patient pathway refers to a patient’s journey from the onset of symptoms to full management across the health-care system [9]. In the case of SLE, which is typically characterized by periods of flare-ups and remissions, the patient journey can be particularly complex, involving interactions with several HCPs, such as primary-care physicians, rheumatologists, dermatologists, nephrologists and other specialists, depending on the organs affected by the disease. In addition, the patient journey may involve various diagnostic tests, imaging studies, laboratory examinations, and therapeutic interventions aimed at controlling disease activity, managing symptoms and preventing long-term complications. Our recent cross-sectional study [9] involving SLE patients, HCPs and various other stakeholders identified numerous key disruption points in SLE patient pathways (Table 1), including the need for appropriate and timely referral strategies, dedicated diagnostic announcement and support consultations, individualized pathways based on patient characteristics, therapeutic patient education, complication prevention strategies, and additional patient support. A new framework for optimizing SLE patient pathways, by addressing these disruption points and implementing tailored interventions, has been developed and validated in consensus meetings with stakeholders, and is currently being implemented in the French region of Alsace. Overall, actively mapping patient pathways provides valuable information for patients, HCPs, organizations and policy-makers, facilitating the development of strategies for improving SLE management and outcomes.

Difficulties in the diagnosis of SLE in Europe

Early diagnosis of SLE remains a significant unmet need in routine clinical practice. As an example, we performed a survey of UK patients with SLE in 2014, in conjunction with Lupus UK [10]. A key observation was that the mean (s.d.) reported time from the first lupus symptom to diagnosis was 6.4 (9.5) years. In addition, 46.9% of respondents had been given a different diagnosis prior to being finally diagnosed with lupus. These results are supported by a study performed in primary care using the UK Clinical Practice Research Datalink (CPRD), where, again, patients were found to have at least one of a range of symptoms for up to 3 years prior to a final diagnosis being made [11]. Our patient survey also found that certain populations, such as men and patients from black backgrounds, had a shorter time to diagnosis [mean (s.d.) 4.8 (8.7) and 2.8 (3.6) years, respectively], potentially because lupus is more unusual in men and because the more severe manifestations are often seen in minority populations [10].

There are a number of potential explanations for these findings. In contrast to LMICs, the long time to diagnosis is unlikely to be due to lack of rheumatologists per capita, as Europe may be better served with rheumatologists and internists who have a special interest in systemic diseases.

Population awareness is likely to be having some affect: while lupus has a similar prevalence to that of other serious conditions, such as multiple sclerosis, leukaemia, etc., in the general population these latter conditions tend to have much greater public awareness.

It is also worth contextualizing the basic epidemiology of lupus to explain why this is a true ‘needle in a haystack’ situation. In the UK, for example, a family doctor is usually responsible for a population of ∼2000 people. This means they may have no more than 1 or 2 lupus patients in their practice population at any given time. A recent estimate of the incidence of lupus estimates ∼3–5 new cases per 100 000 people per annum [12]. Translating this to an individual family doctor’s practice, means that they are likely to see 1 new case of lupus every 10 years, i.e. three times in their professional career!

Another key problem with SLE is that the initial symptoms can often be non-specific. Both in our survey and in the CPRD study, symptoms such as fatigue, a flu-like illness, headaches, joint pains, and RP were all very common early symptoms [10, 11]. Any one of these symptoms on their own can have many other potential explanations. Thus, identifying a lupus patient who presents with fatigue, for example, can be a huge challenge, since there are many other more plausible diagnoses for such a presentation.

It is, therefore, extremely important for specialists to provide guidelines to primary care physicians and other non-specialists about when to consider a diagnosis of lupus. A key opportunity is first to consider patients who are consulting on a frequent basis, particularly if there are a number of different symptoms and signs. Rees et al. reported that patients who were eventually diagnosed with SLE had consulted their GP a median (interquartile range) of 9.2 (5.4–14.7) times per year in the 5 years preceding diagnosis compared, with 3.8 (1.4–7.6) times per year in controls. In addition to the non-specific symptoms outlined above, the addition of more ‘suggestive’ symptoms, such as inflammatory sounding joint pain, light-sensitive rashes, recent hair loss, lymphadenopathy, abnormalities in blood counts and/or a recent thrombosis, increase the likelihood of the patient having SLE. The more of these symptoms that an individual describes, the higher the probability of them having lupus. There have been attempts to try to integrate these symptoms into a model [11] to predict the future risk of a patient developing lupus, and combinations of these factors have been shown to increase the likelihood of developing lupus. Pragmatically, such an approach also has sufficient suggestive potential to indicate the need for blood tests, urine examination, and appropriate antibody testing. The results of objective tests such as these can indicate more increase in the likelihood of lupus and prompt onward referral.

Challenges in LMICs

Health care has not been prioritized by LMICs, with only 5.62% of their gross domestic product (GDP) being invested in it, compared with 14.02% in high-income countries (HICs) [13]; this leads to several problems, including a lower number of physicians and a lower number of beds per 1000 inhabitants in LMICs compared with HICs (1.3 in LMIC vs 3.6 in HIC and 2.3 in LMICs vs 5.3 in HICs, respectively) [14, 15]. In addition, rheumatologists in LMICs are mainly distributed in large cities [16], making it more difficult for patients living in smaller cities and rural settings to be evaluated, leading to a delay in their diagnosis and management.

Even if a patient has medical insurance and the opportunity to be taken care by a rheumatologist, some medications are not available in LMICs. For example, the recently approved therapies for SLE (belimumab, anifrolumab and voclosporin) are not available in many LMICs [5]; furthermore, in the countries in which these treatments are available, they are not always covered by the health-care system, making their access almost impossible for those with a low socio-economic status. This lack of access to new treatments could result in an increase in the daily prednisone dose [17], with the subsequent risk of damage accrual. Drugs that reduce damage accrual are clearly preferred. For example, the new biologics (anifrolumab and belimumab) increase the probability of achieving remission and/or low disease activity [18, 19], and achieving these states has been shown to have a protective effect against damage, mortality, and other relevant outcomes in SLE patients [20].

Unfortunately, in some cases, the cost of the therapy is higher in LMICs than in HICs, and, among LMICs, patients in some middle-income countries pay prices lower than the prices in some low-income countries [21]. Additionally, the threshold for defining a drug as cost-effective should differ between LMICs and HICs, to improve equity; it has been suggested that the threshold should be lower than 1 GDP per capita in LMICs and between 1 and 2 GDP per capita in HICs [22].

To improve access to therapies in LMICs, several actions are needed; for example, to improve early diagnosis, rheumatologists could work in networks, utilizing telehealth, and improve SLE knowledge among general practitioners [23]. Furthermore, rheumatologists can improve health literacy, utilizing social media to deliver information for SLE patients [24]. Additionally, as ethnicity may have an impact on drug response [25], the involvement of patients in LMICs in clinical trials should be encouraged, while taking into account the potential ethical problems associated with the affordability of approved therapies.

Finally, LMICs should work together, promoting the availability of drugs through mass acquisitions, reducing their cost, or encouraging generics and biosimilars via more flexible patent laws [5]. Health technology assessment of these drugs should be undertaken, while recognizing the complexity of diagnosis, disease progression and management, which makes the assessments challenging [26].

The voice of those living with lupus

Managing SLE requires comprehensive and continuous care, making access to health care crucial for patients. In Europe, while there have been significant advancements in medical research and in treatment options for SLE, the patients’ perspective on access to care is a multifaceted landscape.

One of the primary challenges is the delayed diagnosis of SLE, as symptoms can be subtle and mimic other conditions. GPs may not recognize the symptoms, and patients often do not get a referral to a specialist. This means that they frequently embark on a prolonged journey from the onset of symptoms to a confirmed diagnosis, resulting in delayed access to appropriate treatment and management. According to a survey conducted by Lupus Europe in 2020, the average time to diagnosis among European Lupus patients is 2 years [3]. This number increases to 7 years, if there is a prior diagnosis of FM.

The Living with Lupus in 2020 survey results showed that 45% of patients had received another diagnosis prior to their SLE diagnosis, and that the time to diagnosis is significantly influenced by economic status.

Patients across Europe often face disparities in accessing care due to geographical factors. Rural areas may have limited health-care facilities and be a long way from specialized lupus clinics, leading to long travel times and potential delays in receiving timely care. The COVID-19 pandemic accelerated the adoption of telemedicine, offering a potential solution to these barriers. Remote consultations and monitoring enable patients to connect with HCPs without the need for extensive travel, enhancing access to care, especially for those in remote areas. In addition to the problems of geography, the cost of medications can be a significant barrier to access for many patients. Some treatments for SLE are expensive, and not all European countries provide equal financial support or reimbursement for these medications, creating disparities in affordability. Here the lupus patient organizations have a big role to play in advocating and lobbying for better health-care at a national level.

Because SLE is such a complex disease, it requires the expertise of not only rheumatologists but also other specialists. However, many European countries have a shortage of rheumatologists in general, let alone rheumatologists experienced in managing lupus. This leads to long waiting times for appointments and delayed interventions. The specialized “lupus” centres, with multidisciplinary care teams that include rheumatologists, nephrologists, nurses, psychologists, and other specialists, only exist in a few places around Europe. Nevertheless, the lupus centre approach ensures a holistic and coordinated approach to managing SLE, addressing both the medical and psychosocial aspects and providing the best overall care. Providing holistic care becomes even more difficult due to the lack of access to care such as psychology support, physiotherapy, social support, etc. reported by European patients [3].

If the patient is lucky enough to see a specialist, the next issue becomes the communication gap that exists in many cases. Effective communication between HCPs and patients is crucial for managing a chronic disease like SLE [27]. With the many immigrants all across Europe, language barriers and lack of opportunity to have a translator during consultations obstructs the communication and makes shared decision-making impossible. Especially for a heterogeneous disease like SLE, patient education and self-management are important tools for assuring the best treatment, and it is important to supply the patient with the knowledge they need for active participation in their own care.

Patient advocacy groups play a crucial role in raising awareness about SLE and advocating for improved access to care. These groups provide peer-support, information about the disease and available treatments, and platforma on which patients can share their experiences, fostering a sense of community and empowerment.

In Tables 2 and 3, we summarize the ways in which patient organizations, like Lupus Europe, can improve access to care.

Access to care for SLE patients in Europe remains a complex issue with various challenges. While progress has been made in certain areas, addressing geographical disparities, improving timely diagnosis, and ensuring the affordability of medications are ongoing challenges that require concerted efforts from HCPs, policy-makers, and patient advocacy groups. By listening to patients’ perspectives and working collaboratively, Europe can continue to improve the provision of accessible, comprehensive, and patient-centred care for those living with SLE.

How ERNs (particularly ReCONNET) can help improve access to care for SLE patients

ERNs are virtual networks involving HCPs across Europe. Their aim is to improve the care of and outcomes for patients with rare and complex diseases and conditions that require highly specialized treatment and a concentration of knowledge and resources. The ERN ReCONNET, the Network on Connective Tissue and Musculoskeletal Diseases, involves 63 health-care providers from 23 EU Member states and 15 patient representatives who are actively integrated in ERN ReCONNET, the ERN ReCONNET European Patient Advocacy Groups (ePAGs) [8]. The general objectives of ERN ReCONNET are summarized in Table 4.

A number of other strategies are in place to improve access to care for patients with rare and complex diseases, including those with SLE (Table 4). These include the discussion of clinical cases on a dedicated platform, the clinical patient management system (CPMS). This secure platform supports clinicians in diagnosing as well as treating SLE and may serve to facilitate access to care for patients in specialized centres. In addition, the CPMS enables a multidisciplinary discussion of difficult cases, and the ERN RECONNET promotes collaboration with patient advocates and patient associations. ePAGs represent the voice of patients within ERNs, creating a bridge between the ERN and the patient community, ensuring that the ERNs can improve their access to high-quality diagnosis, care and treatment. ePAG Advocates contribute to the development of information for patients, support the dissemination of ERN information and communication to the wider patient community, and engage with the appropriate patient communities for disease-specific activities and projects. An important aspect of the ERN ReCONNET is dissemination and education. ERNs promote activities aimed at improving knowledge of rare and complex diseases: webinars, exchanges between expert centres, the development of lay versions of clinical practice guidelines, and education about red flags to assist the early diagnosis of rare and complex diseases. Finally, the development of patient care pathways is another activity planned by ERN ReCONNET for improving patient care, while fostering the integration of ERNs with the various EU health-care systems. In the framework of ReCONNET, a specific methodological approach was designed in order to provide a reference organizational model for care pathways; the methodological approach is called RarERN Path [28]. This methodology allows integration of the perspectives of large communities of patients, expert clinicians, health economists and HCPs from various EU countries, and is a practical and innovative approach to the creation of organizational models able to shed light on how good organizational practices can meet real-life challenges in rare and complex diseases.

Conclusion

In conclusion, the difficulties of access to care for SLE patients in Europe and worldwide are considerable. The geographical distance between patients and specialized care centers, combined with the scarcity of rheumatologists, exacerbates delays in diagnosis and management, particularly, but not only, in LMICs. Despite these challenges, there are opportunities for improvement. The emergence of telemedicine and digital health technologies offers promising opportunities for overcoming geographical barriers and improving access to specialist care. Concerted action on a more global scale, in which the ERN ReCONNET in Europe is playing a major role, is needed to address these disparities and ensure more equitable access to care for all people living with lupus, regardless of geographical location or socio-economic status. Together, we can work towards a future in which all people living with lupus receive the comprehensive and timely care they deserve.

Supplementary material

Supplementary material is available at Rheumatology online.

Data availability

All data are presented in the manuscript.

Contribution statement

All authors contributed to the conception or design of the work, or the acquisition, analysis, or interpretation of data for the work; all authors contributed to drafting of the manuscript or critically revising it for important intellectual content; all authors approved the final version to be published; all authors agreed to be accountable for all aspects of the work, i.e. to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding

AstraZeneca provided a sponsorship grant towards this independent programme.

Disclosure statement: M.M. has received consulting fees from AstraZeneca, UCB, GSK, Otsuka, and Idorsia, and speaker bureau fees from AstraZeneca, Janssen, UCB and GSK. I.N.B. has received grant support from Janssen, GSK, Astra Zeneca and Novartis, consulting fees from AstraZeneca, Eli Lilly, UCB, GSK, Takeda, Otsuka, Horizon Therapeutics, Dragonfly Therapeutics and Enhance3D Genomics Ltd, and speaker bureau fees from AstraZeneca, Janssen, UCB and GSK. M.F.U.-G. has received grant support from Janssen, consulting fees from AstraZeneca and Ferrer, and speaker fees from AstraZeneca and GSK. J.A. has declared no direct conflict of interest. However, LUPUS EUROPE is funded mostly by grants or donations from Pharmaceutical Companies (Amgen/Horizon, AstraZeneca, Biogen, BMS, Boehringer-Ingelheim, Galapagos, GSK, Idorsia, Janssen, Merck, Novartis, Otsuka, Roche, UCB), none of which exceeds 25% of total funds collected, and none had a say on the content of our studies or work. L.A. has received consulting fees and/or research funding from: Alexion, Amgen, Astra-Zeneca, Abbvie, Alpine, Biogen, BMS, Boehringer-Ingelheim, Chugaï, GSK, Grifols, Janssen-Cilag, Kezar, LFB, Lilly, Medac, Novartis, Pfizer, Roche, and UCB. L.A. is president of the European Lupus Society (SLEuro) and disease coordinator for SLE and relapsing polychondritis within the ERN ReCONNET.

Acknowledgements

The Virtual Roundtable related to this manuscript was supported by an educational grant from AstraZeneca. The latter had no influence on the opinions or views of either the moderator or the speakers, either during the roundtable or in this manuscript. None of the participants has received honoraria from AstraZeneca or from any other third party (including Oxford University Press) to take part in this activity. The authors would like to thank Ms Katia Baumgaertner for her invaluable help in the preparation of the manuscript. INB is a National Institute for Health Research (NIHR) Senior Investigator Emeritus and is supported by the NIHR Manchester Biomedical Research Centre (NIHR203308). The views expressed are those of the author and not necessarily those of the NIHR or Department of Health and Social Care.

References