Characteristics of Late-Onset Spondyloarthritis: Data from the Moroccan Registry of Biological Therapies in Rheumatic Diseases.

Introduction The Assessment of SpondyloArthritis International Society (ASAS) criteria for axial and peripheral spondyloarthritis (SpA) allow for the classification of patients with an age of onset of disease of less than 45 years. However, SpA can start after this age. This study aimed to assess the characteristics of late-onset SpA (SpA>45 years) in the Moroccan registry of biological therapies in rheumatic diseases (RBSMR). Methods A cross-sectional study was conducted using the baseline data of the RBSMR. The protocol for the original RBSMR study was reviewed and approved by the Ethics Committee for Biomedical Research Mohammed V University - Rabat, Faculty of Medicine and Pharmacy of Rabat (approval number for the study was 958/09/19, and the date of approval was September 11, 2019), and all patients had given their written consent. Patients who met the 2009 ASAS criteria for SpA were included. They were divided into two groups: early-onset SpA (≤ 45 years) and late-onset SpA (>45 years). Clinical, biological, radiological, and therapy data of the two groups were compared. Statistical analysis was performed using SPSS v25 software (IBM Corp. Armonk, NY). Parameters with a p-value ≤0.05 were considered significant. Results Our population consisted of 194 patients. Thirty-one patients (16%) had late-onset SpA. Comparison between patients with early-onset (≤45 years) and late-onset SpA (>45 years) revealed that late-onset SpA had a higher tender joint count (p=0.01), a higher swollen joint count (p=0.02), depression (p=0.00), fibromyalgia (p=0.001), hypercholesterolemia (p=0.01), and a lower frequency of coxitis (p=0.008). Logistic regression analysis confirmed that late-onset SpA was associated with a higher tender joint count (OR=0.93, CI 95%: 0.88-0.98), a higher swollen joint count (OR=0.92, CI 95%: 0.85-0.99), depression ( OR=0.19, CI 95%:0.04-0.38), fibromyalgia (OR=1.75, CI 95%: 1.74-17.85), and a lower frequency of coxitis ( OR=0.29, CI 95%: 0.11-0.75). Conclusion As life expectancy increases, late-onset SpA will become increasingly common. It is therefore imperative to determine its characteristics. In the RBSMR study, late-onset SpA was associated with a high number of tender and swollen joints, depression, fibromyalgia, and a lower frequency of coxitis.

Correction: Characteristics of Late-Onset Spondyloarthritis: Data from the Moroccan Registry of Biological Therapies in Rheumatic Diseases.

[This corrects the article DOI: 10.7759/cureus.39100.].

Extra-Articular Manifestations in Patients with Ankylosing Spondylitis: Baseline Characteristics from the RBSMR Study.

Objectives: To describe and analyse the prevalence of extra-articular manifestations (EAMs) including acute anterior uveitis (AAU), psoriasis and inflammatory bowel disease (IBD) in patients with ankylosing spondylitis (AS) in the Moroccan registry of biological therapies in rheumatic diseases RBSMR (Registre des Biothérapies de la Société Marocaine de Rhumatologie). Methods: A cross-sectional, multicentre and analytical study based on the RBSMR database, which included 170 AS. Incidence rates for the development of AAU, psoriasis and IBD were calculated, and risk factors were analysed. Results: Prevalence of EAMs in AS was 13.5%, 4.7% and 11.2% for AAU, psoriasis and IBD respectively. No significant differences were found while establishing a comparison of the prevalence of these EAMs between AS patients with and without peripheral arthritis. Interestingly, AAU was the most common EAM, and was positively associated in multivariable regression with family history of spondyloarthritis (OR= 7.21, CI 95%: 2.23-23.24). Conclusions: AAU was the leading EAM in patients with AS included in the Moroccan biotherapy registry (RBSMR) and it was associated with family history of spondyloarthritis.

Therapeutic Maintenance Level of Methotrexate in Rheumatoid Arthritis: A RBSMR Study.

Objectives: The aim of this study was to determine the therapeutic maintenance level of methotrexate for rheumatoid arthritis patients enrolled in the Moroccan biotherapy registry and to identify predictive factors for discontinuing MTX treatment. Methods: A cross-sectional study was conducted using the baseline data of the Moroccan biotherapy registry for RBSMR (a multicentric study that aims to evaluate tolerance of biological therapy on patients affected with rheumatic diseases). Demographics and disease features were compared using descriptive statistics. Therapeutic maintenance levels were determined according to a Kaplan-Meier survival curve and a univariate Cox proportional hazards regression model was used to compare the strength of potential factors, followed by a multivariate Cox model to identify significant predictors of MTX discontinuation. Statistically significant results were considered for p values less than 0.05. Results: 224 patients with rheumatoid arthritis were included in this study. The mean age of patients was 51.83±11.26 years with a majority of females (87.50%). The median duration of disease was 12 [1.66-41.02] years. The therapeutic maintenance level of MTX was 91.1% at 1 year, 87.1% at 2 years, and 68.3% at 5 years. The median of treatment duration was 2, 02 [0, 46-27,76] years. Causes of treatment interruption were side effects (66/88=75%), inefficiency (12/88=13.63%), and other reasons (10/88=11.36%). Predictive factors for stopping MTX were presence of rheumatoid factor (HR 2.24; 95% CI 1.14-5.15; p=0.02) and the access to education (HR 0.37; 95% CI 0.16-0.88; p=0.02). Conclusion: The therapeutic maintenance level of MTX in our study was satisfactory and comparable to other series, and influenced by many factors such as the occurrence of a side effect. It is necessary to sensitise medical practitioners on symptomatic prevention and management of side effects.

Active tuberculosis infection in moroccan patients with rheumatic diseases under biologic therapy: A multicenter national study.

Background: The aim of this study was to evaluate the prevalence of active tuberculosis (TB) infection in Moroccan patients with rheumatic diseases under biologic therapy, and to describe the demographic characteristics of these patients as well as to explore potential risk factors. Methods: This 14-year nationally representative multicenter study enrolled Moroccan patients with rheumatic diseases who had been treated with biologic therapy. Patient medical records were reviewed retrospectively for demographic characteristics, underlying rheumatic diseases, associated comorbidities, and TB-related data. Results: In total, 1407 eligible patients were studied, detailed records were obtained for only 130 patients; 33 cases with active TB were identified at an estimated prevalence rate of 2.3%. The mean age was 42.9 ± 12 years and 75.8% were males. Ankylosing spondylitis accounted for 84.8% of active TB cases, and the majority of the cases (31/33) occurred among antitumor necrosis factor-alpha (TNF-α) users. A total of 8 out of 33 patients were positive at initial latent TB infection (LTBI) screening by tuberculin skin test and/or interferon-gamma release assay. Consumption of unpasteurized dairy products (odds ratio [OR], 34.841; 95% confidence interval [CI], 3.1-389.7; P = 0.04), diabetes (OR, 38.468; 95% CI, 1.6-878.3; P = 0,022), smoking (OR, 3.941; 95% CI, 1-159.9; P = 0.047), and long biologic therapy duration (OR, 1.991; 95% CI, 1.4-16.3; P = 0.001) were identified as risk factors for developing active TB. Conclusion: Moroccan patients with rheumatic diseases under anti-TNF-α agents are at an increased TB risk, especially when risk factors are present. Strict initial screening and regular monitoring of LTBI is recommended for patients living in high TB prevalence areas.

Prevalence of latent tuberculosis before biotherapy initiation in rheumatoid arthritis and spondyloarthritis: data from the Moroccan biotherapy registry.

Before the initiation of biotherapy in the treatment of rheumatic diseases, it is highly recommended for the patients to be screened for latent tuberculosis infection (LTBI). The objective of this study is to identify the prevalence of LTBI among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) before the initiation of biologic therapy in the Moroccan biotherapy registry (RBSMR). A cross sectional study was conducted using the baseline data of the Moroccan biotherapy registry. Tuberculin skin test or IGRA test or both tests were done before starting anti-TNF treatment for screening LTBI. The comparisons between positive and negative LTBI patients according to rheumatic disease were examined using categorical comparisons. 259 patients were included in this study.94 patients had RA and 165 had SpA. The mean age of the RA patients was 50.49 ± 11.82 years with a majority of females (84%). The mean age for the SpA patients was 36 ± 13.7 years with a majority of males (67.3%). The prevalence of LTBI in the RBSMR was 21.6%. This prevalence was at 24.8% in SpA patients, while it was at 15.9% for RA patients. After the comparison between positive and negative LTBI patients according to rheumatic disease, no demographic, clinical, or therapeutic characteristics were statistically associated with LTBI. This study found that in an endemic TB country like Morocco, a high prevalence of patients with SpA and RA had LTBI, and that RA patients had a lower prevalence than SpA patients.

The first biological choice in patients with rheumatoid arthritis: data from the Moroccan register of biotherapies.

INTRODUCTION: the aim of our study is to determine, from data of the Moroccan register of biotherapies, the factors influencing the choice of the first prescribed biological treatment. METHODS: cross-sectional multicenter study including rheumatoid arthritis patients who were initiated the first biological treatment either: Rituximab, an anti-TNF, or Tocilizumab. The determinants related to the patient and disease have been gathered. A univariate and then multivariate analysis to determine the factors associated with the choice of the first bDMARDs was realized. RESULTS: a total of 225 rheumatoid arthritis patients were included in the Moroccan registry. The mean age was 52 ± 11 years, with female predominance 88% (n = 197). The first prescribed biological treatment was Rituximab 74% (n = 166), the second one was Tocilizumab, 13.6% (n = 31) then comes the anti-TNF in 3rd position with 12.4% (n = 28). The factors associated with the choice of Rituximab as the first line bDMARDs prescribed in univariate analysis were: the insurance type, the positivity of the rheumatoid factor. In multivariate analysis, only the insurance type that remains associated with the choice of Rituximab as the first biological drugs. The Tocilizumab was associated with shorter disease duration and was more prescribed as mono-therapy compared to non Tocilizumab group. TNFi was associated with the insurance type. CONCLUSION: our study suggests that Rituximab and TNFi are associated with the type of insurance and Tocilizumab is the most prescribed biologic mono-therapy in RA patients. Further studies are needed to confirm these results.

One-year direct costs of biological therapy in rheumatoid arthritis and its predictive factors: data from the Moroccan RBSMR registry.

The aim of the study was to estimate the annual direct costs of biological therapies in rheumatoid arthritis (RA), and to establish possible factors associated with those costs. The main data source was the Moroccan registry of biological therapies in rheumatic diseases (RBSMR Registry). We included patients with available 1-year data. Variables related to socio-economic status, disease and biological therapy were collected. Direct costs included prices of biologics, costs of infusions, and subcutaneous injections. Differences in costs across groups were tested by Mann-Whitney and Kruskal-Wallis tests. Correlations analysis was performed in search of factors associated with high costs. We included 197 rheumatoid arthritis patients. The mean age was 52.3 ± 11 years, with female predominance 86.8%. Receiving one of the following therapies: rituximab (n = 132), tocilizumab (n = 37), or TNF-blockers (n = 28). Median one-year direct costs per patient were €1665 [€1472-€9879]. The total annual direct costs were € 978,494. Rituximab, constituted 25.7% of the total annual budget. TNF-blockers and tocilizumab represented 27.3% and 47% of this overall budget, respectively. Although the costs were not significantly different in terms of gender or level of study, the insurance type significantly affected the cost estimation. A positive correlation was found between the annual direct cost and body mass index (r = 0.15, p = 0.04). In Morocco, a developing country, the annual direct costs of biological therapy are high. Our results may contribute to the development of strategies for better governance of these costs.

African League Against Rheumatism (AFLAR) preliminary recommendations on the management of rheumatic diseases during the COVID-19 pandemic.

OBJECTIVES: To develop recommendations for the management of rheumatic and musculoskeletal diseases (RMDs) during the COVID-19 pandemic. METHOD: A task force comprising of 25 rheumatologists from the 5 regions of the continent was formed and operated through a hub-and-spoke model with a central working committee (CWC) and 4 subgroups. The subgroups championed separate scopes of the clinical questions and formulated preliminary statements of recommendations which were processed centrally in the CWC. The CWC and each subgroup met by several virtual meetings, and two rounds of voting were conducted on the drafted statements of recommendations. Votes were online-delivered and recommendations were pruned down according to predefined criteria. Each statement was rated between 1 and 9 with 1-3, 4-6 and 7-9 representing disagreement, uncertainty and agreement, respectively. The levels of agreement on the statements were stratified as low, moderate or high according to the spread of votes. A statement was retired if it had a mean vote below 7 or a 'low' level of agreement. RESULTS: A total of 126 initial statements of recommendations were drafted, and these were reduced to 22 after the two rounds of voting. CONCLUSIONS: The preliminary statements of recommendations will serve to guide the clinical practice of rheumatology across Africa amidst the changing practices and uncertainties in the current era of COVID-19. It is recognized that further updates to the recommendations will be needed as more evidence emerges. Key Points • AFLAR has developed preliminary recommendations for the management of RMDs in the face of the COVID-19 pandemic. • COVID-19 is an unprecedented experience which has brought new concerns regarding the use of some disease-modifying anti-rheumatic drugs (DMARDs), and these recommendations seek to provide guidelines to the African rheumatologists. • Hydroxychloroquine shortage has become rampart across Africa as the drug is being used as prophylaxis against COVID-19 and this may necessitate a review of treatment plan for some patients with RMDs. • Breastfeeding should continue for as long as possible if a woman is positive for SARS-CoV-2 as there is currently no evidence that the infection can be transmitted through breast milk.

The impact of COVID-19 on rheumatology practice across Africa.

OBJECTIVES: To identify the changes in rheumatology service delivery across the five regions of Africa from the impact of the COVID-19 pandemic. METHODS: The COVID-19 African Rheumatology Study Group created an online survey consisting of 40 questions relating to the current practices and experiences of rheumatologists across Africa. The CHERRIES checklist for reporting results of internet e-surveys was adhered to. RESULTS: A total of 554 completed responses were received from 20 countries, which include six in Northern Africa, six in West Africa, four in Southern Africa, three in East Africa and one in Central Africa. Consultant grade rheumatologists constituted 436 (78.7%) of respondents with a mean of 14.5 ± 10.3 years of experience. A total of 77 (13.9%) rheumatologists avoided starting a new biologic. Face-to-face clinics with the use of some personal protective equipment continued to be held in only 293 (52.9%) rheumatologists' practices. Teleconsultation modalities found usage as follows: telephone in 335 (60.5%), WhatsApp in 241 (43.5%), emails in 90 (16.3%) and video calls in 53 (9.6%). Physical examinations were mostly reduced in 295 (53.3%) or done with personal protective equipment in 128 (23.1%) practices. Only 316 (57.0%) reported that the national rheumatology society in their country had produced any recommendation around COVID-19 while only 73 (13.2%) confirmed the availability of a national rheumatology COVID-19 registry in their country. CONCLUSION: COVID-19 has shifted daily rheumatology practices across Africa to more virtual consultations and regional disparities are more apparent in the availability of local protocols and registries.

Targeting Acquired Hemophilia A with Rheumatoid Arthritis by a Rituximab Shot: A Case Report and Review of the Literature.

BACKGROUND Acquired hemophilia A (AH) is a rare hemorrhagic diathesis, characterized by the presence of autoantibodies directed against the pro-coagulant activity of factor VIII. It is associated with rheumatoid arthritis (RA) in 4% to 8% of cases and its prognosis remains severe. CASE REPORT A 66-year-old patient has been followed up for 20 years for deforming and severe RA, which was in low-disease activity. However, the patient presented a polyarticular flare involving the metacarpophalangeal and the proximal interphalangeal joints, the left elbow, and the right knee, which was warm and swollen. Articular puncture of this knee yielded a hematic fluid that did not coagulate. Its cytological analysis showed significant presence of red blood cells, which were also abundantly present in the other cell lines. Activated partial thromboplastin time was lengthened and not corrected by the addition of control plasma. Prothrombin time (Quick's test), fibrinogen level, and vitamin K-dependent factors were without abnormalities. In contrast, factor VIII was collapsed at 7% and the anti-factor VIII antibody was positive. The diagnosis of AH with anti-factor VIII inhibitor was thus retained. With regard to RA, the Disease Activity Score was 6.32 and exhibited a very active RA. Rituximab with methotrexate was begun and the evolution was favorable. After 6 months, the reappearance of the anti-factor VIII inhibitor was found, thus justifying a second cycle of rituximab. CONCLUSIONS AH is not exceptional in RA. Rituximab remains a relevant alternative for managing simultaneous AH with inhibitor and RA.

Performance of quantitative ultrasound and six osteoporosis risk indexes in menopausal women: validation and comparative evaluation study

Background: A number of questionnaire-based systems and the use of portable quantitative ultrasound scanners (QUS) have been devised in an attempt to produce a cost-effective method of screening for osteoporosis.Objective: to assess the sensitivity and specificity of different techniques and their ability to act as screening tools in relation to dual energy X-ray absorptiometry (DXA).Methods: 295 white postmenopausal women aged over 60 were enrolled. Each subject completed a standardized questionnaire which permits the measure of six osteoporosis indexes and had bone mineral density (BMD) measured using QUS and DXA. Sensitivity and specificity of the different techniques in relation to DXA were plotted as receiver-operating characteristic (ROC) curves at DXA T-score total hip ≤ -2.5 (osteoporosis).Results: BUA sensitivity and specificity values were respectively 76.8% and 51.2% at the total hip. The optimal cut-off T-score for QUS was -2 at the total hip. The osteoporosis self-assessment tool (OST) provided consistently the highest AUC (0.80) among the clinical tools and had the best sensitivity and specificity balance (90.2%-44.5%). OST negative likelihood ratio was 0.22.Conclusion: OST (based only on the weight and the age) performed slightly better than QUS and other risk questionnaires in predicting low BMD at the total hip

Osteoporosis, vertebral fractures and metabolic syndrome in postmenopausal women.

BACKGROUND: The combined effect of the metabolic syndrome (MS) risk factors on bone health has led to controversial results and it is still not clear whether this effect is protective or detrimental. The study aimed to examine the association between MS and bone mineral density (BMD), osteoporosis, and vertebral fractures (VFs) among ambulatory older postmenopausal women. METHODS: 270 post-menopausal women with a mean age of 61.0 years ± 7.8 (50 to 90) with no prior known diagnosis of osteoporosis were recruited. BMD and Lateral vertebral fracture assessment (VFA) images were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of Genant semiquantitative approach and morphometry. RESULTS: The MS as defined by the NCEP-ATP III was present in 62 women (23.0%). According to the WHO classification, 82 had osteoporosis at any site (30.4%). VFs were identified in 116 (43.0%): 80 (29.6%) had grade 1 and 36 (13.3%) had grade 2 or 3. Women with MS had a significantly higher BMD and lower prevalence of osteoporosis (17.7% vs. 34.1%) than those without MS. No significant statistical difference was noted in prevalence of VFs (14.5 vs. 13.0%). There were significantly less women with MS among the group of osteoporotic women (13% vs. 27%; p = 0.018). Conditional regression binary analysis assessing the presence of osteoporosis as the dependent variable showed that women with a MS had a significant 71% decrease in the odds of being osteoporotic by BMD compared with women who had not MS accounting for age, BMI, number of parities and years since menopause. CONCLUSION: Women with MS had higher BMD at the hip and spine, suggesting a protective effect of MS on bone. However, the prevalence of VFs was similar between women with or without MS.

The discriminative ability of FRAX, the WHO algorithm, to identify women with prevalent asymptomatic vertebral fractures: a cross-sectional study.

BACKGROUND: A Moroccan model for the FRAX tool to determine the absolute risk of osteoporotic fracture at 10 years has been established recently. The study aimed to assess the discriminative capacity of FRAX in identifying women with prevalent asymptomatic vertebral fractures (VFs). METHODS: We enrolled in this cross-sectional study 908 post-menopausal women with a mean age of 60.9 years ± 7.7 (50 to 91) with no prior known diagnosis of osteoporosis. Subjects were recruited from asymptomatic women selected from the general population. Lateral VFA images and scans of the lumbar spine and proximal femur were obtained using a GE Healthcare Lunar Prodigy densitometer. VFs were defined using a combination of Genantsemiquantitative (SQ) approach and morphometry. We calculated the absolute risk of major fracture and hip fracture with and without bone mineral density (BMD)using the FRAX website.The overall discriminative value of the different risk scores was assessed by calculating the areas under the ROC curve (AUC). RESULTS: VFA images showed that 179 of the participants (19.7%) had at least one grade 2/3 VF. The group of women with VFs had a statistically significant higher FRAX scores for major and hip fractures with and without BMD, and lower weight, height, and lumbar spine and hip BMD and T-scores than those without a VFA-identified VF. The AUC ROC of FRAX for major fracture without BMD was 0.757 (CI 95%; 0.718-0.797) and 0.736 (CI 95%; 0.695-0.777) with BMD, being 0.756 (CI 95%; 0.716-0.796) and 0.747 (CI 95%; 0.709-0.785), respectively for FRAX hip fracture without and with BMD. The AUC ROC of lumbar spine T-score and femoral neck T-score were 0.660 (CI 95%; 0.611-0.708) and 0.707 (CI 95%; 0.664-0.751) respectively. CONCLUSION: In asymptomatic post-menopausal women, the FRAX risk for major fracture without BMD had a better discriminative capacity in identifying the women with prevalent VFs than lumbar spine and femoral neck T-scores suggesting its usefulness in identifying women in whom VFA could be indicated.

Stevens-Johnson syndrome complicating adalimumab therapy in rheumatoid arthritis disease.

The efficacy of adalimumab, a fully human anti-tumor necrosis factor-α recombinant antibody, has dramatically improved the quality of life of patients with rheumatoid and psoriatic arthritis and Crohn's disease. Because it is fully human, one should not expect immune reactions to this molecule. Adverse reactions to adalimumab are limited mainly to injection site reactions and are very common. We, however, report a case of Stevens-Johnson syndrome that required hospitalization and cessation of adalimumab in a patient with rheumatoid arthritis (RA). In this case report, a 53-year-old woman with RA developed severe mucositis, peripheral rash and desquamation and fever concomitant with the fifth dose of 40 mg adalimumab. Infective etiologies were excluded. The patient responded rapidly to IV hydrocortisone and was able to be commenced on infliximab without recurrence of the Stevens-Johnson syndrome. Severe skin reactions induced by TNF-α antagonists can be very serious, and prescribers need to be aware of the potential for the mucocutaneous adverse effects from the use of these agents, particularly due to the significant morbidity and mortality that are associated with SJS.

Prevalence and Risk Factors of Discordance between Left- and Right-Hip Bone Mineral Density Using DXA.

To determine the prevalence of significant left-right differences in hip bone mineral density (BMD), and the impact of this difference on osteoporosis diagnosis, we measured bilateral proximal femora using dual energy X-ray absorptiometry (DXA) in 3481 subjects (608 males, 2873 females). The difference between left and right hip was considered significant if it exceeded the smallest detectable difference (SDD) for any of the three hip subregions. Contralateral femoral BMD was highly correlated at all measuring sites (r = 0.92-0.95). However, significant left-right differences in BMD were common: the difference exceeded the SDD for 54% of patients at total hip, 52.1% at femoral neck, and 57.7% at trochanter. The prevalence of left-right differences was greater in participants >65 years. For 1169 participants with normal spines, 22 (1.9%) had discordant left-right hips in which one hip was osteoporotic; for 1349 patients with osteopenic spines, 94 (7%) had osteoporosis in one hip. Participants with BMI < 20 kg/m(2) were more likely to show major T-score discordance (osteoporosis in one hip and normal BMD in the other). Multiple regression analysis showed that the only significant statically parameter that persists after adjusting for all potential confounding parameters were age over 65 years.