Management of chronic rheumatic diseases in women 18–45 years of age in Asia Pacific: insights from patient and clinician surveys

In women with chronic rheumatic diseases (CRD) such as rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), disease onset, diagnosis and treatment initiation often overlap with their peak reproductive years (18–45 years) [1, 2]. The availability of successful treatment options means that many patients now have improved physical function and quality of life, and may like to consider starting a family [1].

Current EULAR recommendations suggest addressing family planning in all patients of reproductive age, and a multidisciplinary approach to managing these patients [3]. However, most physicians do not proactively discuss family planning with their female patients in this age group. A survey of physicians in the U.S. and in Europe found that only 32–‍56% of them initiated discussions on family planning with their patients [1].

In patients who might be planning to start a family, their ability to conceive may be affected by their disease [4], and they may have worries regarding the impact of disease and treatments on pregnancy. In a 2017 survey conducted in patients in the U.S. and Europe, 54% of women with CRD admitted that they had delayed their decision to start a family, and that their main concern was passing on health issues to the child [5].

During pregnancy, it is important to keep good disease control as active disease at this time can lead to complications and poor pregnancy outcomes, for example preterm birth and growth restriction [6]. Among the biologic disease-modifying antirheumatic drugs (bDMARDs), most tumour necrosis factor inhibitors (TNFi) such as adalimumab, etanercept, infliximab and golimumab may be considered for use in the first and second trimester of pregnancy while certolizumab pegol, an Fc-free TNFi which has little or no placental transfer, may be considered during all three trimesters of pregnancy if clinically needed [3, 7‐9]. Despite the recommendations [3, 7‐10], a previous survey of clinicians in the U.S. and Europe reported a decline in confidence in prescribing TNFi with the onset of family planning as they were concerned about the adverse events (AEs) of the treatments [11]. Inadequate knowledge and general fear towards the compatibility of medications with pregnancy and breastfeeding could result in clinicians unnecessarily discontinuing therapy, thus putting patients at risk of relapse and potential adverse pregnancy outcomes [12‐14].

In the U.S. and Europe, women have reported several fears and misconceptions on these topics and their clinicians also have uncertainties and concerns about the risks and benefits of TNFi in women 18–45 years of age [5, 11]. An online survey was conducted in the APAC region to explore the perspectives of women aged 18–45 years with CRD around disease management, family planning and whether they received support from their clinicians. A separate survey explored clinicians’ attitudes towards treating these women with TNFi. Clinicians were asked about their comfort levels with prescribing TNFi treatment in women 18–45 years of age, decisions around the use of TNFi prior to, during and after pregnancy, and concerns around AEs associated with TNFi during pregnancy.

This study was conducted to explore the perspectives of women aged 18–45 years with CRD around disease management, family planning and whether they received support from their clinicians. The results demonstrate that most women felt that they did not receive all the information they needed to make informed decisions around disease management and pregnancy planning, and lacked an aligned treatment plan between HCPs involved in their care. These women also reported fears regarding pregnancy, such as passing the disease to their child, and misconceptions around treatment and breastfeeding, feeling that they had to choose between breastfeeding and treatment; this was similar across the APAC countries surveyed. Additionally, a separate survey was conducted to understand clinicians’ attitudes towards the use of TNFi in women 18–‍45 years of age with CRD. The study results found that while most clinicians agreed that controlled disease reduced the risk of pregnancy complications, control of disease activity is not yet consistently implemented. Many clinicians were uncertain about the appropriate treatment to use during pregnancy. The results of these surveys highlight a need for improved education and dissemination of information on the management of CRD in women aged 18–‍45 years, for both patients and HCPs.

Disease control is important in the management of CRD in women as active disease may lead to complications during pregnancy and adverse birth outcomes [6, 15, 16]. In this study, the importance of disease control was recognised by many of the APAC clinicians. However, there was still a proportion who were neutral or in disagreement that if a patient’s disease is controlled during pregnancy, it reduces the risk of pregnancy complications, and who did not prioritise disease control during pregnancy. This could be attributed to a lack of understanding of the potential risks associated with discontinuing treatment during pregnancy. Prescribing habits could also be impacted by the lack of experience among clinicians managing CRD in female patients who become pregnant [12]. In a recent study in the U.S. and Europe, 41% of physicians reported having suboptimal skills in adjusting treatment according to the different life stages of their female patients [17]. Similarly, many clinicians in this APAC survey were uncertain about the appropriate treatment to use during pregnancy. Although there are recommendations on the management of CRD in women, clinicians may not be familiar with these due to factors such as language barriers and lack of active dissemination [12]. In addition, clinicians may not know how to apply these recommendations in clinical practice due to a lack of practical guidance and knowledge of who to consult [18]. Development of and access to living documents on medications and patient information, roundtable discussions and small conferences among physicians could be considered to keep physicians updated on improvements in the management of CRD in female patients.

Comfort level with prescribing TNFi in women aged 18–45 years with CRD was generally higher among rheumatologists than obstetricians and orthopaedic surgeons. A recent systematic review identified insufficient knowledge of treatment guidelines and fears around the safety of medication in both mother and fetus as the main factors that influence clinician behaviour in treating women with chronic inflammatory diseases [12]. Similarly, this study found the factors most likely to improve physician comfort with TNFi treatment were more safety data during pregnancy and on the child, and lactation data. In general, orthopaedic surgeons who participated in this survey were more conservative compared with rheumatologists or obstetricians. Orthopaedic surgeons in this study were less comfortable with using TNFi in women aged 18–45 years, more likely to avoid using TNFi during pregnancy and breastfeeding, and around 50% of them did not view disease control as their primary goal during pregnancy. Further studies would be required to look into the reasons behind the conservative approach that clinicians may have, and strategies to overcome them. However, since clinicians are involved in different aspects of patient care, development of practical guidance tailored to the clinician group could be useful to guide them on implementing the evidence into their routine clinical practice.

Despite over 81% of the APAC clinicians reporting that they typically co-manage the auto-immune disease with other specialities during pregnancy, many patients reported that they lacked an aligned treatment plan. According to the results of a patient survey conducted in the U.S., patients wanted their rheumatologists to communicate directly with their obstetrician/gynaecologist, rather than using the patients as an intermediary [19]. Similarly, the results of the APAC survey reported here highlight the need for a clear management plan of shared care and early involvement of multiple stakeholders in all women aged 18–45 years. Communication and exchange of information between the treating physician and the obstetrician/gynaecologist should thus be part of routine care, as patients may consult them independently.

In this study, one in two women in APAC had unaddressed concerns that delayed their decision to get pregnant, the most common being passing on a health issue to their baby. Most women in APAC did not feel fully supported or informed during pregnancy planning and only one-third of them felt they had received all the information they needed during pregnancy. In a survey conducted in the U.S. in women aged 18–45 years with CRD, patients strongly expressed their wish for their rheumatologists to play an active role in their family planning care. The women wanted their rheumatologists to initiate conversations about family planning continuously to provide clear and comprehensive information about their disease and treatments around pregnancy [19]. From interviews conducted with patients with RA in Australia, although most patients depended on their rheumatologist as their primary source of information, there was still an unmet demand for more information, especially around the safety of medication during pregnancy and breastfeeding [20]. This may also be the expectations of the women who participated in this survey. As such, education of clinicians is important for them to initiate and engage in discussions with their patients and to provide consistent, accurate and clear information to patients. The EULAR recommendations for the management of pregnant and lactating patients with rheumatic disease suggested that family planning and adjustment of treatment should be addressed in all patients of reproductive age [3]. A clinical panel in Australia developed a set of clinician-centred, practical suggestions to complement the EULAR recommendations to aid information delivery and clinical practices to support women with RA [18]. The American College of Rheumatology (ACR) has also recently published recommendations on the management of patients with CRD throughout their reproductive lifespan, complementing the current recommendations which focused more on the management of patients who are pregnant and lactating [10]. In previous studies, patients identified that joining a community of people with similar experiences was helpful for social support and sharing their concerns and anxieties around family planning [20, 21]. Given this, clinicians can advise on the availability of patient support groups in their respective regions, for patients to receive additional support in their family planning journey.

The recent ACR recommendations on management of reproductive health in patients with rheumatic diseases suggested many medications, such as hydroxychloroquine, sulfasalazine, rituximab and all TNFi, may be used during lactation [10]. In a prospective cohort study conducted in 2019 in the Netherlands, women with RA were reported to be less likely to breastfeed their baby as compared with the general women population. In the same study, it was reported that the main reason for discontinuation of breastfeeding was the restarting of medication (57.8%, 129/223), although in around 40% of the patients (41.1%, 53/129), their medications were considered compatible with breastfeeding [22]. In this APAC study, more than half of the women felt they had to choose between breastfeeding and treatment. In this survey, more women in Australia did not breastfeed their baby as compared with Japan or Hong Kong/Taiwan, and this was similar to the general population where there was a higher proportion of children who were exclusively breastfed at 6 months in Japan (34.7%) than in Australia (14.0%) [23]. Despite this, the main reason for not breastfeeding was the same across all APAC countries, i.e., a lack of information and fear that the treatment might harm their baby. These results suggest that all patients should be informed about the risk versus benefit of disease control during breastfeeding and all compatible treatment options.

The limitations of these surveys include a lack of formal validation for the questionnaires, a small number of participants, and self-reporting of disease severity by the participants. This study included only women who had successful pregnancies and their experience may be different from those who were unsuccessful. However, this was because this study aimed to understand the women’s experience throughout the whole pregnancy journey, from planning a family, to being pregnant and giving birth. As most respondents were from Australia and Japan, the findings may not be generalisable across the whole of APAC due to diversity in ethnicities and cultural differences. Differences in the responses received may also be attributed to the different social cultures of each country; however, this study was not designed to compare differences between countries. As with epidemiological studies, there may be recall bias as the patients had to recall events from when they were pregnant in the past 2–‍5 years. Patients who had other CRD, such as systemic lupus erythematosus, and clinicians who were managing these patients were not included in this study. These patients and clinicians may face similar challenges, and comparison between the different populations would be helpful to determine if the fears and misconceptions are specific to rheumatic diseases. Questions in the physicians’ survey were also tailored towards TNFi; it may be helpful if attitudes and perceptions around the use of other classes of treatments were assessed. Lastly, as with all surveys, it is important to note that the results may not be truly reflective of the general CRD population, as the sample who participated may have stronger opinions compared with those who did not respond.

In APAC, fears and misconceptions are common among women with CRD. They often had unaddressed concerns and did not feel fully informed in their family planning decisions. Despite many clinicians agreeing that controlled disease reduces the risk of pregnancy complications, control of disease activity was not yet consistently implemented, and many clinicians were uncertain about the appropriate treatments to use during pregnancy. There is a need for patient and physician access to up-to-date and accurate information on the risk versus benefit of different treatment options for disease management in women with CRD. A plain language summary of this manuscript is provided in Supplementary Fig. 4.