Swedish Rheumatism Association Research Articles

Attainment of remission and low disease activity after treatment with belimumab in patients with systemic lupus erythematosus: a post-hoc analysis of pooled data from five randomised clinical trials

Disease remission or low disease activity are key treatment targets for patients with systemic lupus erythematosus (SLE). Pivotal trials of belimumab were conducted before the introduction of these targets. In this study, we aimed to pool data across trials to assess attainment of remission and low disease activity in a large, racially and culturally diverse patient population with SLE. In this integrated post-hoc analysis, we pooled data from five phase 3 trials of belimumab (BLISS-76 [NCT00410384], BLISS-52 [NCT00424476], BLISS-NEA [NCT01345253], BLISS-SC [NCT01484496], and EMBRACE [NCT01632241]), in patients with active, autoantibody-positive SLE. Patients were randomly assigned to receive belimumab (10 mg/kg per month intravenously or 200 mg per week subcutaneously) or placebo, plus standard therapy. The proportion of patients with Definitions of Remission in SLE (DORIS) remission and lupus low disease activity state (LLDAS) were analysed every 4 weeks from week 4 to week 52 for belimumab versus placebo, using modified Poisson regression adjusted for trial variance, in all patients and in subgroups per baseline SLE Disease Activity Index-2000 score (<10 or ≥10); anti-double stranded DNA positivity (yes or no); low complement 3 (C3) or C4 levels (yes or no); anti-dsDNA positivity or low C3 or C4 levels (yes and no); prednisone-equivalent dose (≤7·5 mg per day or >7·5 mg per day); antimalarial use (yes or no); and by race (Black African ancestry or African American, Asian, Indigenous American, or White). Data for 3086 patients (1869 in the belimumab group and 1217 in the placebo group) were analysed. 2913 (94%) of 3086 patients were women and 173 (6%) were men, and the median age was 36 years (IQR 28-45). The proportion of patients with DORIS remission was significantly higher in the belimumab group than the placebo group at weeks 28, 48, and 52 (week 52: 148 [8%] of 1869 participants vs 68 [6%] of 1217 participants; risk ratio 1·51 [95% CI 1·15-1·99]; p=0·0055). The proportion of patients who attained LLDAS was higher in the belimumab group than the placebo group at weeks 8, 24, 32-52 (week 52: 322 [17%] of 1869 participants vs 125 [10%] of 1217 participants; 1·74 [1·44-2·12]; p<0·0001). A higher proportion of patients had DORIS remission at week 52 in the belimumab group than the placebo group among all baseline subgroups denoting high disease activity, with the exception of those on a prednisone-equivalent dose higher than 7·5 mg per day in whom there was no difference for DORIS remission with belimumab versus placebo. The proportion of patients with LLDAS was significantly higher among patients in the belimuab group than those who received placebo from week 44 in all baseline subgroups denoting high disease activity or earlier in some subgroups, and the differences were maintained at week 52. In adults with active SLE, belimumab plus standard therapy yielded greater benefit than placebo plus standard therapy in attaining DORIS remission (for which low rates were attained in both groups) and LLDAS, with differences observed as early as week 28 for DORIS remission and week 8 for LLDAS. Swedish Rheumatism Association, King Gustaf V's 80-year Foundation, Swedish Society of Medicine, Nyckelfonden, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and the Karolinska Institutet.

Temporal trends in adverse pregnancy outcomes in axial spondyloarthritis in Sweden: a cohort study

Evidence on the risks associated with pregnancy and childbirth in women with axial spondyloarthritis is scarce and conflicting, with more research needed to guide policy and clinical practice. We aimed to assess the risks of adverse pregnancy outcomes in a large cohort of women with axial spondyloarthritis, and to investigate how outcomes varied over time and in relation to anti-rheumatic treatment. In this register-based cohort study, we included births in Sweden between April 1, 2007, and Dec 31, 2020, to women with axial spondyloarthritis and general population comparators, matched 1:10 on year of delivery, maternal age, and parity. Our main data source was the Medical Birth Register (MBR), which includes over 98% of births in Sweden and prospectively collects data on antenatal care, delivery, and foetal outcomes. The information in MBR was linked to other registers, including the National Patient Register, the Prescribed Drug Register, and registers with demographic data. Our main outcomes were the relative risks of adverse pregnancy outcomes, analysed using modified Poisson regression. We also studied how the frequency of certain adverse outcomes, as well as disease-modifying antirheumatic drug (DMARD) and non-steroidal anti-inflammatory drug treatments, changed over the study period by linear regression and loess plots. Between April 1, 2007, and Dec 31, 2020, 1580 births in women with axial spondyloarthritis recorded in MBR fulfilled the inclusion criteria and were matched with 15 792 comparator births. Among the 1580 births in women with axial spondyloarthritis, we found increased risks of preterm birth (risk ratio 1·43, 95% CI 1·13-1·80), pre-eclampsia (1·44, 1·08-1·92), elective caesarean delivery (1·59, 1·37-1·84), and serious infant infection (1·29, 1·05-1·59) compared with births in general population comparators. The risks of preterm birth, infant infection, and caesarean delivery decreased by around 0·5 percentage points annually during the study period, while the use of tumour necrosis factor inhibitors during pregnancy increased. In view of remaining concerns regarding safety of the use of biological DMARDs during pregnancy, we saw a reassuring trend in which pregnancy outcomes improved over time in the axial spondyloarthritis group, concurrent with increased use of biological DMARDs. If the current rate of improvement is maintained, women with axial spondyloarthritis treated in accordance with clinical guidelines might eventually not be at an increased risk of adverse pregnancy outcomes. Swedish Research Council and The Swedish Rheumatism Association.

Does being exposed to an educational tool influence patient preferences? The influence of an educational tool on patient preferences assessed by a discrete choice experiment.

ObjectivesThere is an increased interest in patient preferences informing the development and authorisation of medical products. A requirement for robust and meaningful results of such studies is that patients adequately understand the risks and benefits associated with treatments for which their preferences are elicited. This study aims to determine the influence of an educational tool, compared with traditional written information on patient preferences elicited in a discrete choice experiment (DCE). MethodsTreatment preferences of Swedish patients with rheumatoid arthritis (RA) were assessed using a DCE. Patients were recruited via clinics, a research panel, and the Swedish Rheumatism Association. Respondents received training materials either as plain written text or as an online educational tool. The educational tool was designed to enhance understanding of the written text by using graphics, pictograms, icon arrays, spoken text, and click-on functions. Data were analysed using random parameter logit models. Results675 patients with RA were included in the analysis. The patients received either a written information (n = 358) or information via an educational tool (n = 317). Respondents receiving the educational tool placed relatively more importance on all included side effects in their decision making, compared to respondents receiving the written text, who placed greater importance on treatment effectiveness and administration methods. ConclusionCompared to the respondents receiving the written text, the decisions of respondents receiving the educational tool were more influenced by medication side effects. Further research is needed to provide guidance on how and when to use educational tools to inform and elicit patients’ preferences. Practice implicationsThe ways in which attributes are presented to patients significantly impacts preferences measured in a DCE.

Disease Features and Gastrointestinal Microbial Composition in Systemic Sclerosis Patients from Two Independent Cohorts

Background: Previous studies have demonstrated alterations in gastrointestinal (GI) microbiota of patients with systemic sclerosis (SSc). However, these prior studies did not include patients with early SSc, nor examine the impact of disease features on microbial composition. The present study investigated the relationship between SSc features and GI microbiota using two independent, international cohorts. Methods: Prospective SSc patients from Lund University (LU), Sweden, the University of California, Los Angeles (UCLA) and control subjects provided stool specimens for 16S rRNA sequencing. Beta diversity analyses were performed to assess the relationship between disease features and GI microbiota. Multivariate negative binomial models identified differentially abundant genera between groups. Findings: Compared with LU-controls (N=85), early-stage LU-SSc patients (N=106; median disease duration of 2·0 years) had lower abundance of commensal genera (e.g., Faecalibacterium) and increased abundance of pathobiont genera (e.g., Desulfovibrio. Disease features associated with microbial composition (beta diversity) in the LU-SSc patients and UCLA-SSc patients (N=71) included disease duration (P=0·0016), interstitial lung disease (P=0·0030), small intestinal bacterial overgrowth (P=0·0020), and immunosuppression use (P=0·014). After adjusting for these factors, the UCLA-SSc cohort had increased abundance of several pathobiont genera (e.g., Streptococcus) compared with the LU-SSc cohort. Interpretation: This study provides the first evidence that dysbiosis is present early in the SSc disease course. Specific disease features were independently associated with fecal microbial composition in Swedish and American patients. After controlling for these factors, the abundance of pathobiont bacteria differed between cohorts, suggesting that environmental factors affecting the GI microbiota should be considered in future SSc studies. Funding: NHLBI (K23 HL150237-01; ERV), VA (CDA2 IK2CX001717; JPJ), NIH (T32 DA024635; SML), Elizabeth Wallace (ERV); The Swedish Medical Society (KA), The Swedish Rheumatism Association (KA), Stiftelsen Ulla och Roland Gustafssons Donationsfond (KA) and Anna-Greta Crafoords stiftelse (KA). Declaration of Interest: ERV reports the following financial relationships outside of the submitted work: Consulting (Boehringer Ingelheim, Forbius); Research grants (Kadmon, Forbius, Corbus). All other authors have nothing to declare. Ethical Approval: The UCLA Institutional Review Board (#13-001089) and the Regional Ethics Review Board, Lund, Sweden (#2011-596) approved the study protocol and written informed consent was obtained from each participant.

Definitions of remission in systemic lupus erythematosus: a post-hoc analysis of two randomised clinical trials.

The Definitions Of Remission In Systemic Lupus Erythematosus (DORIS) international task force has proposed remission definitions that are amenable to scientific testing. In this study, we aimed to evaluate their suitability as outcome measures in studies of systemic lupus erythematosus. In this post-hoc study, we applied remission definitions as specified by DORIS criteria at multiple timepoints in the BLISS-52 (n=865) and BLISS-76 (n=819) clinical trials. All definitions required physician's global assessment scores less than 0·5 (possible range 0-3). The DORIS 1 definitions required clinical systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K)=0 (with serological items excluded). The DORIS 2 definitions required a score of D or E in all British Isles Lupus Assessment Group (BILAG) domains. The definitions were assessed in the trial populations both with (on therapy) and without (off therapy) treatment allowance-ie, low-dose glucocorticoids (prednisone ≤5 mg/day) and maintenance immunosuppressive and biological agents. Antimalarial agents were allowed in all definitions. The definitions were applied irrespective of serological activity (anti-double stranded DNA positivity, or low C3 or C4) and with normal serology. Finally, we applied modifications similar to DORIS on therapy but allowing higher prednisone doses (≤10 mg/day). In the pooled dataset, the remission definition most frequently attained was the modified (prednisone ≤10 mg/day) DORIS 1a on therapy definition, which required a SLEDAI-2K score of 0 and permitted serological activity (237 [17·8%] of 1333 participants at week 52), followed by the unmodified (predisone ≤5 mg/day) DORIS 1 on therapy definition (140 [10·5%] of 1336 participants at week 52) based on these two definitions. We detected no significant difference between the placebo and belimumab groups. Proportions of patients achieving off therapy and BILAG-based definitions were low (≤0·9% at all timepoints). Sustained attainment of certain on therapy definitions showed an ability to discriminate between patients who received belimumab 10 mg/kg and patients who received placebo. Attainment of DORIS remission definitions was infrequent overall. Use of clinical SLEDAI-2K=0 in the definitions yielded higher proportions of attainment than did use of BILAG D or E. Attainment was also higher using definitions that allowed for serological activity and maintenance treatment. Addition of the durability aspect to on therapy definitions led to an ability to discriminate between belimumab and placebo. Swedish Rheumatism Association, Professor Nanna Svartz Foundation, Ulla and Roland Gustafsson Foundation, Region Stockholm, and Karolinska Institutet Foundations.

Patient Perspectives on the Value of Patient Preference Information in Regulatory Decision Making: A Qualitative Study in Swedish Patients with Rheumatoid Arthritis.

BackgroundThere is increasing interest in involving patient preferences for benefits and risks in regulatory decision making. Therefore, it is essential to identify patient perspectives regarding the value of patient preference information (PPI).ObjectivesThe aim of this study was to explore how patients with rheumatoid arthritis (RA) value the use of PPI in regulatory decision making regarding medical products.MethodsRegulators and patients with RA were interviewed to gather initial insights into opinions on the use of PPI in regulatory decisions regarding medical products. The interviews were used to draft and validate the interview guide for focus groups with patients with RA. Participants were purposively sampled in collaboration with the Swedish Rheumatism Association in Stockholm and Uppsala. Each focus group consisted of three to six patients (18 in total). All interviews were audio-recorded, transcribed verbatim, and analysed using content analysis.ResultsAccording to the participants, PPI could lead to regulators considering patients’ needs, lifestyles and well-being when making decisions. PPI was important in all stages of the medical product lifecycle. Participants reported that, when participating in a preference study, it is important to be well-informed about the use of the study and the development, components, administration, and risks related to the medical products.ConclusionsPatients thought PPI could be valuable to consider in regulatory decisions. It is essential for patients to be well-informed when asked for their preferences. Research on information materials to inform patients in preference studies is needed to increase the value of PPI in regulatory decision making.Electronic supplementary materialThe online version of this article (10.1007/s40271-018-0344-2) contains supplementary material, which is available to authorized users.

Development of a web-based and mobile app to support physical activity in individuals with rheumatoid arthritis: results from the second step of a co-design process.

BackgroundLong-term adherence to physical activity recommendations remains challenging for most individuals with rheumatoid arthritis (RA) despite evidence for its health benefits.ObjectiveThe aim of this study was to provide basic data on system requirement specifications for a Web-based and mobile app to self-manage physical activity. More specifically, we explored the target user group, features of the future app, and correlations between the system requirements and the established behavior change techniques (BCTs).MethodsWe used a participatory action research design. Qualitative data were collected using multiple methods in four workshops. Participants were 5 individuals with RA, a clinical physiotherapist, an officer from the Swedish Rheumatism Association, a Web designer, and 2 physiotherapy researchers. A taxonomy was used to determine the degree of correlation between the system requirements and established BCTs.ResultsParticipants agreed that the future Web-based and mobile app should be based on two major components important for maintaining physical activity: (1) a calendar feature for goal setting, planning, and recording of physical activity performance and progress, and (2) a small community feature for positive feedback and support from peers. All system requirements correlated with established BCTs, which were coded as 24 different BCTs.ConclusionsTo our knowledge, this study is the first to involve individuals with RA as co-designers, in collaboration with clinicians, researchers, and Web designers, to produce basic data to generate system requirement specifications for an eHealth service. The system requirements correlated to the BCTs, making specifications of content and future evaluation of effectiveness possible.

Ethical review boards are poor advocates for patient perspectives

In medical research, patients are increasingly recognized with ‘lay knowledge’ but their views are poorly researched. The study objective was to investigate patients’ attitudes to medical research. This is in comparison to lay and expert members on ethical review boards (ERB), as their task is to evaluate the risk−benefits of research, which are ultimately grounded in attitudes and values. From focus-group interviews with patients suffering from chronic inflammatory diseases, a postal questionnaire was developed and sent to patient members of the Swedish Rheumatism Association ( n = 1195) and to all ERB board members in Sweden ( N = 583). Response rates were 65 percent and the surveys were conducted in Jan−May 2011. Agreement across the groups included priority for medical research on diagnostic and early detection of disease. A key difference was expert and lay ERB members giving higher priority to basic research/research on lifestyle and prevention (primarily benefiting future patients), whereas patients prioritized research on daily function. On this significant point, lay members did not share the opinion of this patient group, indicating that they may be poor representatives for patients’ views. These results call for further research: how can patient perspectives be included in ERB discussions and in what way should patients’ values influence the research agenda.

SP0049 Strategy for Work for People with Rheumatic Diseases

Most people with rheumatic diseases both can and want to work. Many people are already working but more people could do it if the circumstances where right.The Swedish Rheumatism Association...

AB0078 Effect of Mpges-1 Targeting on Lipid Metabolism in Human Cells

BackgroundMicrosomal prostaglandin E synthase-1 (mPGES-1) is the terminal enzyme in the induced PGE2 production and well-recognized target for the development of novel anti-inflammatory drugs. Genetic deletion and inhibition of mPGES-1...

OP0288-PARE Pain School “Knowledge for Life” Makes Life Easier for People with Chronic Pain

BackgroundThe training course Pain School “Knowledge for Life” was developed in collaboration between the Swedish Rheumatism Association, Sahlgrenska University Hospital/physiotherapy and Primary Care Middle-Älvsborg. The Pain School “Knowledge for Life”...

OP0249-PARE High Demand of RA-Instructor Training Program of Healthcare Staff

BackgroundIn 1988 the University of Texas, Southwestern Medical Center (UTSW) started “Arthritis Educator Program”. The purpose was to improve rheumatology training of future physicians using patients with rheumatoid arthritis. However...

FRI0575-HPR “A Gift from Heaven' or 'This was not for Me” – A Mixed Methods Approach to Describe Experiences of Physical Activity Participation among Persons with Rheumatoid Arthritis

BackgroundA large proportion of persons with rheumatoid arthritis (RA) do not meet recommendations on health-enhancing physical activity (HEPA) (1). We performed a complex theory-based intervention in a group format at...

FRI0567-HPR Criterion Validation of the Submaximal ÅStrand Bicycle Test to Estimate Aerobic Capacity in People with Rheumatoid Arthritis

BackgroundAerobic capacity tests are important to evaluate exercise programs and to encourage individuals to a physically active lifestyle. Maximum aerobic tests in a laboratory setting are expensive and not always...

Patient-initiated research in rheumatic diseases in Sweden--dignity, identity and quality of life in focus when patients set the research agenda.

Patients' involvement in healthcare and research has been a growing area in the last few decades. The World Health Organization (WHO) emphasizes the importance of personalized care of the chronic diseases in order to optimize care and treatment for the individual patient (WHO, 2005). In rheumatology, this has been highlighted by different organizations, such as The European League against Rheumatism (EULAR) (de Wit et al., 2013) and Outcome Measures in Rheumatology (OMERACT) (Kirwan et al., 2009), in order to increase the involvement of patients' perspective in care and research. The rheumatic diseases consist of 80–100 diagnoses, and about 1 million people in Sweden are affected. The most common rheumatic diseases are rheumatoid arthritis, ankylosing spondylitis, osteoarthritis and chronic pain/fibromyalgia. The common denominators of the rheumatic diseases are that they are usually long lasting and affect the daily life of the patient, including pain, fatigue and problems with physical activity and function. Previous research has shown that patients' perspectives of rheumatic diseases are insufficiently illuminated and that there are differences between patients' and health professionals' perspectives in relation to the rheumatic diseases and their consequences (Fair, 2003; Gorter et al., 2002; Stinson et al., 2008; Zangi et al., 2011). For example, patients focus on their illness experience and health professionals focus on the diseases in a general way. The quality of an encounter depends on the health professional's communications skills (Fair, 2003). Studies have shown that patients with rheumatic disease have needs that are not met by health services. Unmet needs are described as a lack of continuity, a lack of discussion with patients about the physical consequences of their disease and the need of patients to be treated as a person rather than as a disease (Bergsten et al., 2011; Kjeken et al., 2006; Lacaille et al., 2007; Leung et al., 2009; Sanderson et al., 2011). Patients' interests in health care and in research are highlighted as important aspects of the future of healthcare. The Swedish Rheumatism Association (the national patient organization) and the Foundation of Research and Development at Spenshult decided to carry out a joint project to develop patient-initiated research into the rheumatic diseases. The project aimed to follow the working process of involving patients in a project group and to describe the research issues that were important from the patient's point of view.

Patients’ attitudes towards animal testing: “To conduct research on animals is, I suppose, a necessary evil”

A strong argument for the practice of animal testing in medical research is the potential benefit to patients in getting improved pain relief, minimising morbidity and mortality. However, patients’ opinions on the ethics of animal testing are seldom sought, despite their role as principal stakeholders. This study compared the attitudes of patients and researchers on animal testing. Focus-group interviews were held with patients suffering from chronic inflammatory diseases, resulting in a questionnaire that was distributed January–May 2011. The questionnaire was posted to patient members of the Swedish Rheumatism Association (n=1195) and to all scientific experts serving on Ethical Review Boards in Sweden (n=364), with response rates of 65 per cent and 60 per cent, respectively. Results show that patients hold a positive stance towards animal testing, but with many caveats, and the level of support is comparable to those held by the general public found in national surveys. A clear majority of researchers were positive towards animal testing, and large statistical differences between patients and researchers were found regarding their attitudes towards testing animals commonly held as pets (P<0.001). Women were more critical than men regarding which species are used for what purposes (P<0.001). Researchers need to be aware that their more positive attitude towards animal testing is not shared to an equal degree with patients, who are the intended end-users and beneficiaries of medical research. The moral basis for using animals in research needs to be further discussed by all stakeholders.

PARE0005 Educational partnership between sweden and estonia

BackgroundKnowledge Transfer Programme is an annual programme developed by EULAR Standing Committee of PARE which provides a defined grant to the educational visit programme. The programme designed for patient organisations...

OP0310-PARE From One-Way Communication to Dialogue, Facebook and Twitter

BackgroundThe Swedish Rheumatism Association (SRA) has in recent years invested heavily in being seen in social media. In 2010 SRA launched Anne’s photo blog, describing Anne Carlsson (SRA president) daily...

OP0265-PARE National Guidelines for Musculoskeletal Diseases in Sweden

BackgroundIn Sweden the National Board of Health and Welfare develop National (NBHW) guidelines to support those who make decisions concerning the allocation of resources within Health and Medical Care and...

PARE0017 A piece of cake - an excellent way to unite reseachers and donors

BackgroundFor many years The Swedish Rheumatism association has supported rheumatology research through fundraising activities. This is a growing business and a development area within the organization. To become a successful...