Adverse Impact of Systemic Lupus Erythematosus on Pregnancy Outcomes: A Saudi Arabia Retrospective Multi-Center Study.

Objective: The current study aimed to determine the pregnancy outcomes complications in patients with SLE and its association with clinical, laboratory variables, disease activity, and medication use in the Saudi population, as well as pregnancy effect on disease activity. Methods: A multicenter study included pregnant female patients with Systemic Lupus Erythematosus (SLE) from three tertiary centers in Saudi Arabia. The demographics, clinical, and laboratory variables, SLE disease activity index (SLEDAI), medication before, during, and after pregnancy, planned pregnancy, pregnancy-related outcomes, and complications in comparison to age-matched healthy female controls were noted. Results: A total of 66 pregnant patients with SLE and 93 healthy age-matched pregnant controls were included in the study. A total of 77.3% had SLEDAI-2K ≤ 4 before conception, and 84.85% of pregnancies were planned. Age of conception, cesarean section, miscarriage, and low birth weight were statistically significant (p <0.05) higher in SLE patients than in healthy controls. Among all clinical and laboratory variables, SLEDAI-2K > 4 and active lupus nephritis during pregnancy were statistically associated with adverse outcomes (p <0.05), history of lupus nephritis was not associated with statistically adverse pregnancy outcomes. Higher SLEDAI-2K > 4 was an independent risk at least 4.87 times higher association with adverse pregnancy outcomes. (p <0.05). Conclusion: SLE is intricately connected with unfavorable pregnancy outcomes. The preconception of high disease activity stands as a pivotal risk factor for adverse outcomes. Despite the disease remission and meticulous planning, SLE patients frequently grapple with disease exacerbations during pregnancy, culminating in unexpected and unfavorable pregnancy-related outcomes. This underscores the intricate and multifaceted nature of managing SLE during gestation.

Methodology for the adolopment of recommendations for the treatment of rheumatoid arthritis in the Kingdom of Saudi Arabia.

BACKGROUND: Currently, there are no guidelines for the treatment of rheumatoid arthritis (RA) tailored to the context of the Kingdom of Saudi Arabia (KSA). Adaptation of guidelines accounts for contextual factors and becomes more efficient than de novo guideline development when relevant, good quality, and up-to-date guidelines are available. The objective of this study is to describe the methodology used for the adolopment of the 2021 American College of Rheumatology (ACR) guidelines for the treatment of RA in the KSA. METHODS: We followed the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE)-ADOLOPMENT methodology. The adolopment KSA panel included relevant stakeholders and leading contributors to the original guidelines. We developed a list of five adaptation-relevant prioritization criteria that the panelists applied to the original recommendations. We updated the original evidence profiles with newly published studies identified by the panelists. We constructed Evidence to Decision (EtD) tables including contextual information from the KSA setting. We used the PanelVoice function of GRADEPro Guideline Development Tool (GDT) to obtain the panel's judgments on the EtD criteria ahead of the panel meeting. Following the meeting, we used the PANELVIEW instrument to obtain the panel's evaluation of the process. RESULTS: The KSA panel prioritized five recommendations, for which one evidence profile required updating. Out of five adoloped recommendations, two were modified in terms of direction, and one was modified in terms of certainty of the evidence. Criteria driving the modifications in direction were valuation of outcomes, balance of effects, cost, and acceptability. The mean score on the 7-point scale items of the PANELVIEW instrument had an average of 6.47 (SD = 0.18) across all items. CONCLUSION: The GRADE-ADOLOPMENT methodology proved to be efficient. The panel assessed the process and outcome positively. Engagement of stakeholders proved to be important for the success of this project.

The Impact of Spondyloarthritis on Health-Related Quality of Life and Healthcare Resource Utilization in Saudi Arabia: A Narrative Review and Directions for Future Research.

Spondylarthritis (SpA) is an umbrella term that encompasses a wide range of rheumatological disorders. Several studies demonstrated that SpA is associated with increased healthcare resource utilization (HCRU) and a lower health-related quality of life (HRQoL). This review aimed to summarize the current literature regarding the multidimensional impact of SpA on HRQoL and HCRU in Saudi Arabia and explore the correlation of the extent of severity of SpA with HRQoL and HCRU. Although the prevalence of SpA varies across different populations and is correlated with HLA-B27 prevalence, the magnitude of SpA in the Saudi population has not been extensively evaluated. Few studies have investigated the impact of SpA on HRQoL and HCRU in Saudi Arabia and the Middle East. There is a need to study the cost-effectiveness of various SpA treatment strategies, including biologic disease-modifying anti-rheumatic drugs (bDMARDs), to prioritize healthcare spending in the Saudi healthcare system. Data on SpA in Saudi Arabia and the Middle East region are mainly based on expert views, with few population-based studies compared to other regions. Therefore, there is an imperative need to develop high-quality, national-level epidemiological studies that assess the following: (1) more accurate estimates of the current prevalence of SpA in Saudi Arabia, including the prevalence of axial SpA and psoriatic arthritis; (2) the phenotypes/clinical characteristics of SpA, including disease severity and extra-articular involvement; (3) the impact of SpA on the HRQoL of the patients and the factors that can predict the extent of impaired HRQoL in such population, which can represent the first step in developing psychological interventions that should be personalized to this patient population; (4) the impact of implementing formal assessment of disease activity on the management of the patients and, subsequently, their HRQoL; and (5) the HCRU and costs for patients with SpA, and how treatment patterns can affect this cost.

Recommendations for the treatment of rheumatoid arthritis in Saudi Arabia: adolopment of the 2021 American College of Rheumatology guidelines.

BACKGROUND: The 2021 American College of Rheumatology (ACR) rheumatoid arthritis (RA) guideline considers the specific context of the United States which differs from that of Saudi Arabia in many aspects that may impact recommendations. The objective of this project was to adapt a set of prioritized recommendations from the 2021 ACR guideline for the treatment of rheumatoid arthritis RA for the context of Saudi Arabia, by the Saudi Society for Rheumatology (SSR). METHODS: The process followed the GRADE-ADOLOPMENT methodology, and the reporting adhered to the RIGHT-Ad@pt checklist. Working groups included a coordination group and a 19-member panel representing different stakeholder groups. The Evidence to Decision (EtD) tables included evidence on health effects from the source guideline and contextual information from the Saudi setting. RESULTS: The panel prioritized and adapted five recommendations from the source guideline. The process led to modifying two out of the five prioritized recommendations, all listed here. In naive patients with low disease activity, methotrexate (MTX) is conditionally recommended over sulfasalazine (SSZ) (modified direction); hydroxychloroquine (HCQ) is conditionally recommended over SSZ (unmodified). Initiation of csDMARDs with short-term glucocorticoids is conditionally recommended over csDMARDs alone in naive patients with moderate to high disease activity (modified direction). Switch to subcutaneous MTX is conditionally recommended over addition/switch to alternative DMARD(s) in patients taking oral MTX who are not at target (unmodified). Discontinuation of MTX is conditionally recommended over gradual discontinuation of the bDMARD or tsDMARD for patients taking MTX plus a bDMARD or tsDMARD who wish to discontinue a DMARD (unmodified). CONCLUSION: Rheumatologists practicing in Saudi Arabia can use the adoloped recommendations generated by this project while adopting the rest of the recommendations from the 2021 ACR guidelines.

Perception of Biosimilar Biologics and Non-Medical Prescription Switching among Rheumatologists: A Saudi Society for Rheumatology Initiative.

BACKGROUND: The aim of this study was to evaluate rheumatologists' perceptions of biosimilar biologics and Non-Medical Switching (NMS). METHODS: A cross-sectional survey was conducted among registered members of the Saudi Society for Rheumatology. The questionnaire focused on biosimilars and NMS. Logistic regression was performed to ascertain the effect of demographics and practice characteristics on the use of biosimilars and NMS. RESULTS: Out of 249 SSR members, 143 completed the survey, generating a response rate of 57.4%. Of those (59.44%) were men with a mean (±SD) age and years of practice of 42.3 ± 9.13 and 10.3 ± 8.9, respectively. Rheumatologists managing adult patients (81.82%) and Ministry of Health practice (43.36 %) were the majority of respondents. Previous experience in prescribing a biosimilar was reported by 43 (30.07%) participants, with a higher probability among women (p = 0.015). A total of 26 (18.18%) participants had performed NMS on eligible patients. Adequate knowledge on biosimilars was reported by 69 (48.25%) participants. The adequacy of evidence to grant biosimilar approval for the studied indication and extrapolation to treat other conditions was reported by 88 (61.5%) and 69 (48.3%), respectively. The concept of totality-of-the-evidence was well understood by 37.1%. Biosimilars had been previously used by 43 (30.07) participants in their practice. NMS had been attempted by 26 (18.18), while 86 (60.1%) participants believed that NMS might harm patients. CONCLUSION: There is a clear knowledge gap about the biosimilar approval process among adult and pediatric rheumatologists who took part in the survey. In addition, a large number of participants reported having negative opinions about NMS. There is a need to organize SSR-led educational activities, and develop national guidelines regarding biosimilars and NMS.

Expert recommendations on early diagnosis and referral of axial spondyloarthritis in the Kingdom of Saudi Arabia.

Axial spondyloarthritis is a chronic inflammatory disorder that primarily involves the axial skeleton (sacroiliac joints and spine), causing stiffness, severe pain and fatigue. In some patients, definitive structural damage of sacroiliac joints is visible on imaging and is known as radiographic axial spondyloarthritis. Some patients do not have a clear radiographic damage of the sacroiliac joints, and this subtype is known as non-radiographic axial spondyloarthritis. Early diagnosis is important for reducing the risk of irreversible structural damage and disability. Management of axial spondyloarthritis is challenging in Saudi Arabia because of inadequate disease knowledge and the unavailability of local guidelines. Therefore, this expert consensus is intended to provide recommendations, including the referral pathway, the definition of remission and the treat-to-target approach, to all healthcare professionals for the management of patients with axial spondyloarthritis. A Delphi technique of consensus was developed by involving an expert panel of 10 rheumatologists, 1 dermatologist and 1 general physician. The experts offered consensus-based recommendations based on a review of available scientific evidence and clinical experience for the referral, screening and management of patients with axial spondyloarthritis.

Consensus-based recommendations on the diagnosis, referral and clinical management of patients with psoriatic arthritis.

Psoriatic arthritis (PsA) is a highly heterogeneous disease with complex manifestations. Limited understanding of the disease and non-availability of local guidelines pose challenges in the management of PsA in Saudi Arabia. Therefore, this expert consensus is aimed to provide recommendations on the management of patients with PsA, including referral pathway, definition of remission and treat-to-target (T2T) approach. A Delphi technique of consensus development was used involving an expert panel comprised of 10 rheumatologists, one dermatologist and one family physician. Based on the review of available published evidence and the opinions of clinical experts, key recommendations were developed. A consensus was achieved in defining the following: management guideline adaptable for Saudi Arabia, most useful screening tool, laboratory investigations, imaging tests and criteria for referring suspected PsA patients to a rheumatologist. In addition, an agreement was achieved in defining the T2T strategy and remission for the clinical management of PsA. Overall, these recommendations provide an evidence-based framework for the management of PsA patients in Saudi Arabia.

Adverse Impact of Rheumatoid Arthritis on Pregnancy Outcomes: A Saudi Arabia Prospective Multicenter Study.

BACKGROUND: Rheumatoid arthritis (RA) is associated with adverse pregnancy outcomes and postpartum complications, especially with severe disease activity. OBJECTIVE: The current study aimed to compare the pregnancy outcomes in patients with RA and healthy controls as well as to assess the impact of disease-related variables, medications and disease activity on pregnancy and neonatal-related outcomes in the Saudi population. METHODS: This prospective multicenter study included pregnant female patients with RA from three tertiary centers in Saudi Arabia. The demographics, disease activity scoring (DAS28-CRP), medication before and during pregnancy, pregnancy-related outcomes, and complications in comparison to age-matched healthy female controls were noted. RESULTS: A total of 77 pregnant patients with RA and 250 healthy age-matched pregnant controls were included in the study. A total of 67.53% were in remission before conception (DAS28CRP ≤2.6), and 81.8% of pregnancies were planned. Age of conception, preterm labor, neonatal intensive care unit (NICU) admission and low birth weight were statistically significant (p <0.05) and higher in RA patients than in healthy controls. Longer disease duration (p <0.001), and high C-reactive protein and erythrocyte sedimentation rate levels before conception (p ≤0.001) were statistically associated with preterm NICU admission. There was statistically significant association between mild (p = 0.015) or moderate to severe DAS28-CRP (p = 0.001) and RA patients regarding pregnancy outcomes. The classification table obtained from the logistic model showed patients with mild and moderate-severe DAS28-CRP have significantly high chances of having an adverse pregnancy outcome. CONCLUSION: RA has a negative impact on pregnancy-related outcomes. Higher disease activity is considered a major risk; thus, tight disease control should be aimed. Planned pregnancy follow-up is associated with better pregnancy outcomes.

Improving the understanding of originator and biosimilar biologics among healthcare providers in Saudi Arabia.

The loss of patentability of many originator biologics has led to the rapid introduction of biosimilar agents. The anticipated economic benefit of introducing such agent has been accompanied by vagueness surrounding their biotechnology, approval requirements, positioning in treatment paradigms and potential for adverse events. The Second Symposium on Biologics and Biosimilars "Beyond Clinical Practice" was held on 24th-26th January 2020 aiming at improving the understanding of these new agents in a diverse interactive conference and to guide stakeholders how to introduce biosimilars into clinical practice. The symposium consisted of 4 tracks and 3 workshops. A total of 217 participants attended the meeting. The majority were pharmacists (78.8%) followed by physicians (18.9%) and other healthcare providers (2.3%). The workshops covered the following topics: basics of pharmacoeconomics, pharmacovigilance and patients' perspective toward biosimilar biologics. While, the 4 main tracks included: Introduction to biosimilars, challenges in clinical practice, regulatory and pharmacoeconomic aspects and Challenges in biosimilar pharmacovigilance.

Prevalence and associated factors of resting electrocardiogram abnormalities among systemic lupus erythematosus patients without cardiovascular disease.

BACKGROUND: Electrocardiogram (ECG) cardiovascular disease (CVD) abnormalities (ECG-CVD) are predictive of subsequent CVD events in the general population. Systemic lupus erythematosus (SLE) patients are vulnerable to CVD. We aimed to determine the prevalence of ECG-CVD in SLE patients and to examine the risk factors associated with ECG-CVD. METHODS: A 12-lead resting supine ECG was performed on consecutive adult patients attending the clinic. One cardiologist interpreted the ECGs. ECG-CVD were defined as the presence of one or more of the following 4 elements (ECG-4): ST-segment and/or T-wave abnormalities, left ventricular hypertrophy (LVH), left axis deviation (LAD), left bundle branch block (LBBB) and right bundle branch block (RBBB). ECG-5 included the same elements as ECG-4 and the Q-wave. Repeated measurement data were created and the associations between ECG-4/ECG-5 and demographics were evaluated with univariate and multivariate Cox regression models. RESULTS: Of 487 SLE patients, 104 (21.4%) and 118 (24.2%) patients had one or more of the ECG-4 and ECG-5 elements, respectively. A higher prevalence of ECG-CVD was found in patients with a longer SLE disease duration, and the burden of ECG-CVD elements increased with age. Increased age, active SLE disease, and damage were associated with ECG4 and ECG-5, while treatment of hyperlipidemia was protective. CONCLUSION: A high prevalence of ECG-4 (21.4%) and ECG-5 (24.2%) was found in this SLE cohort. Controlling SLE disease activity is important since it was associated with ECG-4 and ECG-5. Early identification of ECG-4 and ECG-5 in SLE patients might allow for better stratification and risk management.

Recent advances in the biologic therapy of lupus: the 10 most important areas to look for common pitfalls in clinical trials.

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease affecting different organs. The improved knowledge of the disease's pathogenesis has contributed to the emergence of immune targets and new biologic drugs directed at them. Although rheumatologists continue to use off-label biologics in SLE resistant to other immunosuppressants, only belimumab has been approved as a biological therapy since 2011. AREAS COVERED: In this review, an overview is provided on: 1) the classification of the biologic drugs in clinical trials and of those under research; 2) the results of clinical trials of biologic therapy with an interpretation of pitfalls and syntheses of potential approaches to overcome these pitfalls and, 3) the commonly used disease activity metrics and composite indices for assessing response to drugs. EXPERT OPINION: Some drugs that have failed in previous drug trials have shown to be efficacious in the treatment of lupus in observational studies. Moreover, the post-hoc analyses of the data of negative drug trials have shown that results of the same trials could be altered with the modification of some pitfalls. For future clinical trials, the consideration of these pitfalls is crucial when designing clinical trials. This could potentially enhance the approval of novel drugs for SLE.

Challenges of diagnosis and management of axial spondyloarthritis in North Africa and the Middle East: An expert consensus.

Axial spondyloarthritis (SpA) is a spectrum of inflammatory disease with stages characterized by both nonradiographic and radiographic sacroiliitis. Nonradiographic axial SpA is associated with health-related quality-of-life impairment and may progress to ankylosing spondylitis. Axial SpA has a low prevalence in some countries in North Africa and the Middle East, and pooling of data and resources is needed to increase understanding of the regional picture. Early diagnosis and effective treatment are required to reduce disease burden and prevent progression. Anti-TNF therapy is recommended for patients with persistently high disease activity despite conventional treatment, and has been shown to be effective in patients without radiographic damage. Diagnostic delays can be an obstacle to early treatment and appropriate referral strategies are needed. In some countries, restricted access to magnetic resonance imaging and anti-TNF agents presents a challenge. In this article, a group of experts from North Africa and the Middle East evaluated the diagnosis and management of axial SpA with particular reference to this region.

2015 Guidelines for Osteoporosis in Saudi Arabia: Recommendations from the Saudi Osteoporosis Society.

BACKGROUND AND OBJECTIVES: To provide guidelines for medical professionals in Saudi Arabia regarding osteoporosis. DESIGN AND SETTINGS: A panel of 14 local experts in osteoporosis assembled to provide consensus based on the strength of evidence and expert opinions on osteoporosis treatment. PATIENTS AND METHODS: The Saudi Osteoporosis Society (SOS) formed a panel of experts who performed an extensive published studies search to formulate recommendations regarding prevention, diagnosis, and treatment of osteoporosis in Saudi Arabia. Both local and international published studies were utilized whenever available. RESULTS: Dual x-ray absorptiometry (DXA) scanning is still the golden standard for assessing bone mineral density (BMD). In the absence of local, country-specific fracture risk assessment tool (FRAX), the SOS recommends using the USA (White) version of the FRAX tool. All women above 60 years of age should be evaluated for BMD. This is because the panel recognized that osteoporosis and osteoporotic fractures occur at a younger age in Saudi Arabia. Hormone replacement therapy (HRT) is not recommended for treating postmenopausal women with osteoporosis. BMD evaluation should be performed 1-2 years after initiating intervention, and the assessment of bone turnover biomarkers should be performed whenever available to determine the efficacy of intervention. CONCLUSION: All Saudi women above the age of 60 years must undergo a BMD assessment using DXA. Therapy decisions should be formulated with the use of the USA (White) version of the FRAX tool.

Clinical Assessment and Management of Spondyloarthritides in the Middle East: A Multinational Investigation.

Data on spondyloarthritis (SpA) from the Middle East are sparse and the management of these diseases in this area of the world faces a number of challenges, including the relevant resources to enable early diagnosis and referral and sufficient funds to aid the most appropriate treatment strategy. The objective was to report on the characteristics, disease burden, and treatment of SpA in the Middle East region and to highlight where management strategies could be improved, with the overall aim of achieving better patient outcomes. This multicenter, observational, cross-sectional study collected demographic, clinical, laboratory, and treatment data on 169 consecutive SpA patients at four centers (Egypt, Kuwait, Qatar, and Saudi Arabia). The data collected presents the average time from symptom onset to diagnosis along with the presence of comorbidities in the region and comparisons between treatment with NSAIDs and biologics. In the absence of regional registries of SpA patients, the data presented here provide a rare snapshot of the characteristics, disease burden, and treatment of these patients, highlighting the management challenges in the region.

Profile of epratuzumab and its potential in the treatment of systemic lupus erythematosus.

Management of systemic lupus erythematosus (SLE) represents a fascinating, emerging field. Research has recently provided us with a better understanding of the immunologic alterations of SLE, leading to the creation of immunomodulatory agents designed to disrupt specific cell targets and pro-inflammatory pathways. Despite the improvement in the prognosis of SLE in the last 50 years with the use of immunosuppressive therapy such as cyclophosphamide and mycophenolate mofetil, cytotoxicity remains a major complication of these medications and the need for more specific targeted immunotherapy is increasing. Early recognition and treatment of SLE with targeted immunotherapy has the potential to improve quality of life and reduce the risk of disease flare-ups and complications. In this review, we will explore the role of B-cells in the pathogenesis of SLE highlighting current insights into SLE development and management. In addition, we will discuss epratuzumab's role in the treatment of SLE. Epratuzumab is a humanized anti-CD22 monoclonal antibody that targets CD22 on B-cell and its role in B-cell modulation, migration, function, and inhibition of B-cell receptor signaling. Epratuzumab is currently in a Phase III study evaluating its efficacy in the management of moderate to severe SLE. All published trials on epratuzumab have shown great promise with safe profiles.

Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that causes substantial morbidity. As is typical for many other multifactorial disorders, much of the heritability of SLE remains unknown. We identified a rare autosomal recessive form of SLE, in which autozygome analysis revealed a null mutation in the DNASE1L3 gene. The DNASE1L3-related SLE we describe was always pediatric in onset and correlated with a high frequency of lupus nephritis. Our findings confirm the critical role of impaired clearance of degraded DNA in SLE pathogenesis.

Thalidomide for treatment of severe generalized discoid lupus lesions in two patients with systemic lupus erythematosus.

We describe 2 patients with systemic lupus erythematous whose widespread discoid lupus erythematosus was unresponsive to systemic steroids and antimalarial agents. They showed dramatic improvement to thalidomide at a dose of 300 mg/d, with maximum benefit achieved within 15 weeks of therapy. Dosages of 50 to 100 mg/d were effective in maintaining remission for 1 year. However, thalidomide-induced neuropathy was observed in both cases.