Risk factors for severe COVID-19 outcomes: a study of immune-mediated inflammatory diseases, immunomodulatory medications, and comorbidities in a large US healthcare system (preprint)

Background COVID-19 outcomes, in the context of immune-mediated inflammatory diseases (IMIDs), are incompletely understood. Reported outcomes vary considerably depending on the patient population studied. It is essential to analyse data for a large population, while considering the effects of the pandemic time period, comorbidities, long term use of immunomodulatory medications (IMMs), and vaccination status. Methods In this retrospective case-control study, patients of all ages with IMIDs were identified from a large U.S. healthcare system. COVID-19 infections were identified based on SARS-CoV-2 NAAT test results. Controls without IMIDs were selected from the same database. Severe outcomes were hospitalisation, mechanical ventilation (MV), and death. We analysed data from 1 March 2020 to 30 August 2022, looking separately at both pre-Omicron and Omicron predominant periods. Factors including IMID diagnoses, comorbidities, long term use of IMMs, and vaccination and booster status were analysed using multivariable logistic regression (LR) and extreme gradient boosting (XGB). Findings Out of 2 167 656 patients tested for SARS-CoV-2, there were 290 855 with confirmed COVID-19 infection: 15 397 patients with IMIDs and 275 458 controls (patients without IMIDs). Age and most chronic comorbidities were risk factors for worse outcomes, whereas vaccination and boosters were protective. Patients with IMIDs had higher rates of hospitalisation and mortality compared with controls. However, in multivariable analyses, few IMIDs were rarely risk factors for worse outcomes. Further, asthma, psoriasis and spondyloarthritis were associated with reduced risk. Most IMMs had no significant association, but less frequently used IMM drugs were limited by sample size. XGB outperformed LR, with the AUROCs for models across different time periods and outcomes ranging from 0.77 to 0.92. Interpretation For patients with IMIDs, as for controls, age and comorbidities were risk factors for worse COVID-19 outcomes, whereas vaccinations were protective. Most IMIDs and immunomodulatory therapies were not associated with more severe outcomes. Interestingly, asthma, psoriasis and spondyloarthritis were associated with less severe COVID-19 outcomes than those expected for the population overall. These results can help inform clinical, policy and research decisions. Funding Pfizer, Novartis, Janssen, NIH

HLA-B27 did not protect against COVID-19 in patients with axial Spondyloarthritis – Data from the ReumaCov-Brasil Registry (preprint)

Background Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. Aim To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. Methods The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), with (cases) and without (control group) COVID-19 diagnosis, were paired to sex and age. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanic ventilation and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. Results From May 24th, 2020 to Jan 24th, 2021, a total of 269 axial SpA patients were included, of whom 165 (61.3%) with COVID-19 and 104 (38.7%) without COVID-19. Most of them were men (N = 153; 56.9%) with mean age of 46.3 ± 13.8 years and long-term disease (13.1 ± 9.9 years). There were no significant statistically differences concerning social distancing, smoking, BMI, waist circumference and comorbidities. Regarding b-DMARDs, 134 (75.3%) were on TNF inhibitors and 17 (9.6%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 45, 73.8% vs. n = 38, 73.1%, respectively; p = 0.93). In addition, disease activity was similar before and after the infection. On the other hand, the control group had significantly higher disease activity score, according to ASDAS-CRP (2.8 ± 1.8 vs. 1.8 ± 1.2, p = 0.03). Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.2 ± 3.6 days, with length of hospitalization quite similar between patients who died and those discharged (12.6 ± 7 and 13.9 ± 11.7, respectively). The global death estimation for COVID-19 was 1.9 (95%CI 0.6–4.3), regardless HLA-B27 status. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. Conclusions No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. Trial registration: This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials – REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

Prevalence and factors associated with flares following COVID-19 mRNA vaccination in patients with rheumatoid arthritis, psoriatic arthritis and spondyloarthritis: a national cohort study (preprint)

Objective To determine prevalence and factors associated with flares post Coronavirus disease 2019 (COVID-19) mRNA vaccination in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and spondyloarthritis (SpA). Methods A retrospective multi-centre study was conducted (January 2021 to February 2022). Data were collected during index visit, defined as first post-vaccine visit in which the patient had a physician-defined flare, or if at least three months had elapsed since first vaccine dose, whichever came first. Factors associated with flares were identified using mixed effects Cox regression and expressed as hazard ratio (HR) and 95% confidence interval (CI). Results Total of 2377 patients were included (1563 RA, 415 PsA and 399 SpA). Among patients with RA, PsA and SpA, 21.3%, 24.1% and 21.8% experienced a flare respectively. Of those who experienced a flare, only 10.2%, 11.0% and 14.9% were severe in patients with RA, PsA and SpA respectively. Patients with low or moderate/ high disease were more likely to flare compared to those in remission in patients with RA only (HR: 1.68, 95% CI: 1.22 – 2.31; HR: 2.28, 95% CI: 1.50 – 3.48, respectively). Receiving the Moderna vaccine was associated with a higher HR of flare compared to the Pfizer vaccine in patients with PsA only (HR: 2.21, 95% CI: 1.20 – 4.08). Patients who had two vaccine doses were found to be less likely to flare (HR: 0.08, 95% CI: 0.06 – 0.10). HRs of flares were not significantly different among RA, PsA and SpA. Conclusion About one-fifth of patients experienced a disease flare post COVID-19 mRNA vaccination, but most flares were non-severe. Patients with active disease prior to vaccination should be monitored closely for disease flares, especially in patients with RA.

Immune responses and disease biomarker long-term changes following COVID-19 mRNA vaccination in a cohort of rheumatic disease patients (preprint)

Objective. To evaluate seroreactivity and disease biomarkers after 2 or 3 doses of COVID-19 mRNA vaccines in a cohort of patients with rheumatic diseases. Methods. We collected biological samples longitudinally before and after 2-3 doses of COVID-19 mRNA vaccines from a cohort of patients with systemic lupus erythematosus (SLE), psoriatic arthritis, Sjogrens syndrome, ankylosing spondylitis, and inflammatory myositis. Anti-SARS-CoV-2 spike IgG and IgA and anti-dsDNA concentration were measured by ELISA. A surrogate neutralization assay was utilized to measure antibody neutralization ability. Lupus disease activity was measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Expression of type I interferon signature was measured by real-time PCR. The frequency of extrafollicular double negative 2 (DN2) B cells was measured by flow cytometry. Results. Most of the patients generated high SARS-CoV-2 spike-specific neutralizing antibodies comparable to those in healthy controls after 2 doses of mRNA vaccines. The antibody level declined over time but recovered after the third dose of the vaccine. Rituximab treatment substantially reduced antibody level and neutralization ability. Among SLE patients, no consistent increase in SLEDAI scores was observed post-vaccination. The changes in anti-dsDNA antibody concentration and expression of type I IFN signature genes were highly variable but did not show consistent or significant increases. Frequency of DN2 B cells remained largely stable. Conclusion. Rheumatic disease patients without rituximab treatment have robust antibody responses toward COVID-19 mRNA vaccination. Disease activity and disease-associated biomarkers remain largely stable over 3 doses of vaccines, suggesting that COVID-19 mRNA vaccines may not exacerbate rheumatic diseases.

Incidence of rheumatic diseases during the COVID-19 pandemic in South Korea.

BACKGROUND/AIMS: The recent coronavirus disease 2019 (COVID-19) pandemic has been associated with changes in the epidemiology of not only infectious diseases but also several non-infectious conditions. This study investigated changes in the recorded incidence of various rheumatic diseases during the COVID-19 pandemic. METHODS: The number of patients for each disease from January 2016 to December 2020 was obtained from the Korean Health Insurance Review and Assessment Service database. We compared the incidence of nine rheumatic diseases (seropositive rheumatoid arthritis, systemic lupus erythematosus [SLE], idiopathic inflammatory myositis [IIM], ankylosing spondylitis [AS], systemic sclerosis, Sjögren's syndrome, Behçet's disease [BD], polymyalgia rheumatica, and gout) and hypertensive diseases to control for changes in healthcare utilisation before and after the COVID-19 outbreak. The disease incidence before and after the COVID-19 outbreak was compared using the autoregressive integrated moving average (ARIMA) and quasi- Poisson analyses. RESULTS: Compared with the predicted incidence in 2020 using the ARIMA model, the monthly incidence of SLE, BD, AS, and gout temporarily significantly decreased, whereas other rheumatic diseases and hypertensive diseases were within the 95% confidence interval (CI) of the predicted values in the first half of 2020. In age- and sex-adjusted quasi-Poisson regression analysis, the annual incidences of IIM (rate ratio [RR], 0.473; 95% CI, 0.307 to 0.697), SLE (RR, 0.845; 95% CI, 0.798 to 0.895), and BD (RR, 0.850; 95% CI, 0.796 to 0.906) were significantly decreased compared with those in the previous 4 years. CONCLUSION: The recorded annual incidence of some rheumatic diseases, including IIM, SLE, and BD, decreased during the COVID-19 pandemic.

Effectiveness and safety of generic tofacitinib in spondyloarthritis: A real-world retrospective analysis from India.

BACKGROUND: Clinical trial evidence demonstrates the efficacy of tofacitinib in ankylosing spondylitis and psoriatic arthritis (PsA). Real-world data from spondyloarthritis (SpA) patients are scarce; there are few reports of its effectiveness and safety from low- to middle-income countries like India, despite its widespread usage. METHODS: This was a retrospective analysis of clinical and laboratory records of 100 patients with SpA prescribed generic tofacitinib from a single center in Mumbai, India. Disease activity was measured using the Ankylosing Spondylitis Disease Activity Score C-Reactive Protein (ASDAS-CRP) in all patients, along with disease-specific outcome measures in the subgroups. We used paired t test for response to tofacitinib. We compared Δ ASDAS-CRP in patients with active peripheral arthritis and in patients without. We defined clinical tofacitinib failure as the physician's decision to change or add a disease-modifying antirheumatic drug (DMARD), and performed logistic regression to identify factors associated with tofacitinib failure. RESULTS: Among 100 patients (71 male, median age 42.5 years), 57 had axial SpA, 10 had peripheral SpA, 4 had inflammatory bowel disease-SpA and 29 had PsA. One-third had received biologic DMARDs previously. Patients received tofacitinib for a median of 192 days. There was a significant improvement in ASDAS-CRP in all types of SpA. Patients with active peripheral arthritis had a significantly greater fall in ASDAS-CRP. There were no serious adverse events, 19 patients had mild COVID-19; no patient had tuberculosis. Ten patients had tofacitinib failure; no baseline parameter could predict failure. INTERPRETATION: In the real-world setting, generic tofacitinib showed good effectiveness and tolerable safety profile in Indian patients with SpA.

The Profile of COVID-19 in Patients with Autoimmune Disease: A Case Series.

Autoimmune diseases are known to be a risk factor for severe COVID-19 infection. This is the first case series of patients with autoimmune disease suffering from COVID-19 infection in Jakarta, Indonesia. There were 12 confirmed cases of COVID-19 infection in autoimmune patients from March 2020 until February 2021. We select 5 patients in this case series. Three of them had systemic lupus erythematous (SLE), one of them had rheumatoid arthritis, and one of them had ankylosing spondylitis. Three of them had high BSR Risk Stratification. Most of them had used daily steroid therapy. Fatigue, abdominal pain, diarrhea, and cough were the common symptoms found.  None of the patients were admitted to ICU, used mechanical ventilators, and all of them survived. Most of the patients were prescribed anti-coagulant therapy. This first comprehensive case series can provide valuable information regarding the clinical characteristics of COVID-19 infection in the Indonesian autoimmune disorder patient population.

Investigation of changes in ankylosing spondylitis disease activity through 2021 COVID-19 wave in Taiwan by using electronic medical record management system.

We aim to investigate the alteration in disease activity of ankylosing spondylitis (AS) individuals before, during, and after the COVID-19 wave in Taiwan by using electronic medical-record management system (EMRMS). We identified 126 AS individuals from the single center, and gathered data of the three disease activities (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score with erythrocyte sedimentation rate [ASDAS-ESR], and Ankylosing Spondylitis Disease Activity Score with C-Reactive Protein [ASDAS-CRP]) by using EMRMS before (7 February to 1 May, 2021), during (2 May to 24 July, 2021), and after the COVID-19 wave (25 July to 16 October, 2021). We compared the disease activity measures of the three phases through a paired t test. Among the 126 individuals, CRP was significantly higher during the COVID-19 wave (0.2 (0.1, 0.5) mg/dl, p = 0.001) than before the wave (0.2 (0.1, 0.4) mg/dl), ESR (8.0 (4.0, 15.0) mm/h, p = 0.003) and ASDAS-ESR (1.4 (1.0, 1.9), p = 0.032) were significantly higher after the wave than during the wave (6.0 (3.0, 12.0) mm/h and 1.2 (0.9, 1.8) mm/h) e. ESR, CRP, ASDAS-ESR and ASDAS-CRP were all significant higher after COVID-19 wave than before. The disease activities of AS individuals in Taiwan worsened after 2021 COVID-19 wave in Taiwan.

COVID-19 in Patients with Systemic Inflammatory Diseases: Impact on Disease Activity.

INTRODUCTION: COVID-19 pandemic, an international emergency, raised concerns about the interaction of this infection and disease-modifying drugs used in the treatment of Systemic inflammatory diseases (SID). Understanding the relationship between COVID-19 and disease activity is crucial to adapt the treatment. AIM: The aim of our study was to determine the impact of COVID-19 on the disease activity of rheumatic diseases. PATIENTS AND METHODS: We performed a cross-sectional study, including patients with SID (rheumatoid arthritis (RA) and spondyloarthritis (SpA)). Disease activity was evaluated during the last check-up before COVID-19 and within the period of 6 months after the infection. Activity scores were assessed with Disease Activity Score (DAS28) for RA and Ankylosing Spondylitis Disease Activity Score (ASDAS) for SpA. Correlation and regression coefficients were used to evaluate associations among the variables. RESULTS AND DISCUSSION: Totally, thirty-two patients were included; twenty followed for RA and twelve for axial SpA. The mean disease duration of the underlying rheumatic disease was 10.2 years (2-30). RA was seropositive and erosive in 61% and 31%, respectively. Seventeen patients were on csDMARDs: 14 were on Methotrexate and three patients were on Salazopyrine. Ten patients (31%) were treated with bDMARDs; Tumor necrosis factor (TNF)-alpha inhibitors were used in eight cases. Rituximab and secukinumab were prescribed for one patient each. In 70%, COVID-19 was pauci-symptomatic. A severe form with a need for hospitalization was noted in 9%. Two patients were admitted to the intensive care unit (ICU). Overall, treatment with DMARDs was interrupted in all cases: when COVID-19 symptoms began in 82% and when PCR was positive in 18%. Both RA and axial SpA were not active after a mean period of 6 months after COVID-19 infection (p = 0.818 and p = 0.626, respectively). CONCLUSION: Although our patients interrupted their DMARDs, our study demonstrates that disease activity as assessed by ASDAS and DAS28 in SpA and RA remained unchanged after COVID-19.

Evaluation of the frequency and intensity of COVID-19 in patients with ankylosing spondylitis under anti-TNF therapy.

BACKGROUND: Dear Editor, After the coronavirus disease 2019 (COVID-19) pandemic affected the whole world, rheumatologists began to think about how COVID-19 will progress in patients with inflammatory conditions. High cytokine levels play a role in the pathophysiology of COVID-19 infection. Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine known to have a key role in the pathogenesis of chronic immune-mediated diseases. AntiTNF therapy may cause an increase in active tuberculosis, other granulomatous diseases, and serious infections [1]. According to many studies, rheumatological diseases have not been identified as a risk factor for severe COVID-19 infection [2]. Should significantly increased cytokine levels during COVID-19 infection make us consider anticytokine therapies that may be used in the treatment of patients with COVID-19 a risk? We aimed to explore whether the frequency of COVID-19 infection increased, the effect of comorbidities on the frequency of infection, and whether the severity of the disease and need for intensive care support increased in patients who used anti-TNF agents. We performed a retrospective case-control study between March and December 2020 in Sakarya University Training and Research Hospital. Retrospectively, we evaluated whether there was a difference in the frequency and severity of COVID-19 in our patients diagnosed with ankylosing spondylitis (AS), 77 of whom were using anti-TNF and 49 of whom didn't use anti-TNF. Hospitalization and intensive care unit (ICU) requirements were evaluated as endpoints. In the anti-TNF group, patients used adalimumab, etanercept, certolizumab, infliximab, and golimumab. Patients were questioned at an outpatient clinic in person or by phone. Seventy-seven patients with AS using anti-TNF agents (58 males, 19 females) and 49 patients with AS (38 males, 11 females) not using anti-TNF agents were included in the study (p = 0.943). Mean age of patients using antiTNF agents was 41.53 ± 10.38, and mean age of patients not using anti-TNF agents was 42.94 ± 10.86 (p = 0.468). Thirty-three (42.9%) patients were smokers in the antiTNF group, while 23 (46.9%) patients were smokers in the group not using TNFi (p = 0.791). There was 12 pack-year smoking in the anti-TNF group, and 14 pack-year smoking in not using TNFi (p = 0.623). The frequency of diabetes mellitus (DM), hypertension (HT), amiloidosis, familial mediterranean fever (FMF), coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD) was similar in both groups (p = 0.403, p = 0.999, p = 0.521, p = 0.999, p = 0.999, respectively). Six patients using TNFi and 3 patients not using TNFi recovered from COVID-19 infection. However, this result was not statistically significant (p = 0.999). One patient using anti-TNF was hospitalized but with no need for admission to the ICU (p = 0.999). All 9 patients recovering from COVID-19 were male (p = 0.113). There were 2 (22.2%) smokers in the SARS-CoV-2 positive group and 54 (46.2%) smokers in SARS-CoV-2 negative group (p = 0.297). There was 37.5 pack-year smoking in SARS-CoV-2 positive group, and 12 pack-year smoking in SARS-CoV-2 negative group (p = 0.151). Nobody has comorbidities (DM, HT, amiloidosis, FMF, CAD, COPD) in SARS-CoV-2 positive group. There were patients with DM (5.1%), HT (15.4%), amiloidosis (1.7%), FMF (1.7%), CAD (0.9%) and COPD (0.9%) in SARS-CoV-2 negative group (p = 0.999, p = 0.356, p = 0.999, p = 0.999, p = 0.999, p = 0.999, respectively). Having comorbidities was not detected to be associated with frequency of COVID-19. 31 (40.3%) patients were using adalimumab, 25 (32.5%) patients were using etanercept, 13 patients were using (16.9%) certolizumab, 6 (7.8%) patients were using golimumab, and 2 patients (2.6%) were using infliximab in TNF group. Six patients using anti-TNF (2 adalimumab, 1 etanercept, 1 golimumab,2 infliximab) and 3 nonuser patients recovered from COVID-19 (p = 0.999). No statistically significant difference was found between SARS-CoV-2 positive and negative patients in terms of the types of anti TNF they used. Patients were called in March 2020, and they were advised to terminate their anti-TNF therapy, when the COVID-19 pandemic began. Among those who used antiTNF, 2 (33.3%) people who had COVID-19 and 38 (53.5%) people who did not have COVID-19 interrupted treatment (p = 0.419). Anti-TNF users who did not have COVID-19 stopped taking the treatment for an average of 3 months (min 2-max 4 months) starting from March 2020, and the patients who had COVID-19 (p = 0.102) stopped taking the treatment for 1.5 months (min 1-max 2 months). Duration of interrupting TNFi was not significant for the risk of COVID-19. Comorbidities, older age, and the presence of active disease have been associated with worse outcomes in previous studies [3]. In our study, the anti-TNF using and the nonuser groups were similar according to age, sex, and comorbidities. Although comorbidities in COVID-19 are associated with severe disease in the literature, we did not find a significant difference in our study. This result is probably related to our insufficient number of patients. As a result, we found that the use of anti-TNF did not increase the frequency and severity of COVID-19. In a recently published multicenter study, it was stated that the use of biological DMARDs in patients with inflammatory rheumatic diseases was not significantly associated with a worse outcome of COVID-19. But unlike our study, having no comorbidities was associated with a decreased risk of a worse outcome [4]. There are currently studies investigating the therapeutic utility of infliximab and adalimumab in hospitalized COVID-19 patients [5]. The results of these studies are very important. The usability of TNFi in treatment and at which stage of the disease anti-TNF agents can be used are wondered. We will see the course of the disease all over the world after the administration of the COVID-19 vaccines, but we still need more information about effective and safe treatment. RESULTS: The authors declare that there is no conflict of interest. DISCUSSION: The authors did not receive support from any organization for this work.

Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY (preprint)

ObjectiveTo use the OpenSAFELY platform to replicate key metrics from a national clinical audit, and assess the impact of COVID-19 on disease incidence and care delivery for inflammatory arthritis (IA) in England. DesignPopulation-based cohort study, with the approval of NHS England. SettingPrimary care and linked hospital outpatient data for more than 17 million people registered with general practices in England that use TPP electronic health record software. ParticipantsAdults (18-110 years) with new diagnoses of IA (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, undifferentiated IA) between 1 April 2019 and 31 March 2022. Main outcome measuresThe following outcomes were explored before and after April 2020: 1) incidence of IA diagnoses; 2) time from primary care referral to first rheumatology assessment; 3) time to first prescription of a disease-modifying anti-rheumatic drug (DMARD) in primary care. ResultsFrom a reference population of 17,683,500 adults, there were 31,280 incident IA diagnoses between April 2019 and March 2022. The incidence of IA decreased by 20.3% in the year commencing April 2020, relative to the preceding year (5.1 vs. 6.4 diagnoses per 10,000 adults, respectively). For those who presented with IA, the time to first rheumatology assessment was shorter during the pandemic (median 18 days; interquartile range 8 to 35 days) than before (21 days; 9 to 41 days). Overall, the proportion of patients prescribed DMARDs in primary care was comparable during the pandemic to before; however, the choice of medication changed, with fewer people prescribed methotrexate or leflunomide during the pandemic, and more people prescribed sulfasalazine or hydroxychloroquine. ConclusionsThe incidence of IA diagnoses in England decreased markedly during the early COVID-19 pandemic. However, for people who sought medical attention, the impact of the pandemic on service delivery was less marked than might have been anticipated. This study demonstrates that it is feasible to use routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality for long-term conditions on a national scale, without the need for manual data collection.

Sex-Based Medicine Meets Psoriatic Arthritis: Lessons Learned and to Learn.

Humorally associated autoimmune diseases generally show a female predominance whereas ankylosing spondylitis, a disease that overlaps with psoriatic arthritis (PsA), shows a male predominance. The present review ascertains the current knowledge of sex-specific differences related to psoriatic arthritis (PsA), a chronic, inflammatory condition associated with psoriasis. Sex differences may have important implications for clinical research in PsA and in terms of epidemiology (incidence, prevalence, lifetime risk, survival, and mortality), clinical, radiological, and laboratory features, and response to treatment. While nationwide surveys and large-scale databases and registries show no sex-specific differences, varying male/female ratios have been reported, ranging from 0.42 to 2.75 (comparable with those reported for psoriasis vulgaris: ranging from 0.28 to 2.38). This may reflect subtle, complex, nonlinear interactions between the biological make-up of the individual (genetic and epigenetic differences), hormonal components including menopausal status, environmental exposures including skeletal physical stressing, and psychological variables. There exists methodological heterogeneity and paucity of data concerning sex-specific differences, in terms of the specific population studied, study design, and the diagnostic criteria utilized. Harmonizing and reconciling these discrepancies would be of crucial importance in achieving the ambitious goals of personalized/individualized medicine and further standardized meta-data and Big Data could help disentangle and elucidate the precise mechanisms of underlying potential PsA sex-specific differences.

Reply to: "Herpes zoster seven days after SARS-CoV-2 vaccination in a patient with ankylosing spondylitis under adalimumab" by Josef Finsterer.

Not available.

Tele-yoga in the management of Ankylosing Spondylitis amidst COVID pandemic: A Prospective Randomized Controlled Trial (preprint)

Patients with Ankylosing Spondylitis (AS) often report mental and physical problems and have a poor quality of life (QoL). This study intended to investigate the efficacy of a 3-months tele-yogic intervention on the disease activity, inflammatory markers, and mental health measures in patients with AS. Hundred and twenty AS patients were assigned to either the yoga intervention or control arm. The yoga intervention arm (YG) (n = 57) received a 60-minutes structured yoga module for 3-months on online in addition to standard medical care. The control (CG) participants (n = 52) followed only standard care for the same period. BASDAI, BASFI, ASQOL, psychological and inflammatory biomarkers were assessed at baseline and three months. YG showed significant improvement in BASDAI (p = 0.001), anxiety (p = 0.0004), and depression (p = 0.001) at 3-months compared to the baseline. The CG showed no change. After 3-months, the intervention resulted in a significant improvement in BASDI (-0.79; 95% CI (-1.3, to -0.29); p = 0.0021),BASFI (-0.86; 95% CI (-1.59, to -0.14); p = 0.0193), anxiety (-0.42; 95% CI (-0.84 to -0.01); p = 0.0468), and AS-QoL (-3.37; 95% CI (-5.21, to 1.53); p = 0.0004) compared to the CG. The present study suggests that Yoga helps to improve the pain, functional index, and mental health among patients with AS. The tele-yoga intervention is feasible and effective in the management of AS.

Home-based rehabilitation in patients over 60 with stabilized ankylosing spondylitis during the COVID-19 pandemic.

BACKGROUND: COVID-19 has become a significant healthcare issue, particularly challenging for patients with ankylosing spondylitis (AS), because immune-related diseases and their treatments could adversely affect the susceptibility to or severity of a viral infection. OBJECTIVE: This study is conducted to present an exercise rehabilitation program that patients older than 60 years with AS can do at home during the COVID-19 pandemic. METHODS: Three Delphi surveys were conducted to reach a consensus on home-based rehabilitation programs. This study recruited ten experts and performed three Delphi rounds for a month. RESULTS: The expert panel suggested that home-based rehabilitation for the patients should be carried out with a clear rehabilitation goal. Their final recommendations are to institute a program aimed to ease symptoms, such as pain and stiffness; encourage patients to consult with experts regularly to ensure that they perform exercise rehabilitation properly at home; add fast walking and stretching to the rehabilitation program; and see if indoor cycling, Pilates, or yoga could be appropriate. CONCLUSIONS: This study suggests that patients with AS over 60 should repeat low-intensity exercises, such as stretching, for an hour a day, four to six times a week during the COVID-19 pandemic.

Different Covid-19 Outcomes Among Systemic Rheumatic Diseases: A Nation-wide Cohort Study (preprint)

Background: Nationwide data at a country level on Covid-19 in unvaccinated patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) are scarce. Methods: By interlinking data from national electronic registries, covering nearly 99% of the Greek population (approximately 11,000,000), between March 2020 and February 2021, when vaccination became available, we recorded confirmed infections and Covid-19-associated hospitalizations and deaths in essentially all adult patients with RA, AS, PsA, SLE, and SSc under treatment (n=74,970, median age of 67.5, 51.2, 58.1, 56.2, 62.2 years, respectively) and in individually matched (1:5) on age, sex, and region of domicile random comparators from the general population. Results: Binary logistic regression analysis after adjusting for age, sex and biologic agents, revealed that RA, PsA, SLE and SSc, but not AS patients, had significantly higher risk of infection (by 43%, 25%, 20% and 49%, respectively), and hospitalization for Covid-19 (by 81%, 56%, 94%, and 111%, respectively), possibly due, at least in part, to increased testing and lower threshold for admission. Patients with RA and SSc had indeed higher Covid-19 associated mortality rates [OR:1.86 (95% CI 1.37 to 2.52) and OR:2.90 (95% CI 0.97 to 8.67), respectively] compared to the general population. Each additional year of age increased the risk of hospitalization for Covid-19 by 3% (OR 1.030, 95% CI: 1.028 to 1.034) and the risk of Covid-19 related death by 8% (OR 1.08, 95% CI: 1.07 to 1.09), independently of gender, systemic rheumatic disease, and biologic agents. A further analysis using AS patients as the reference category, adjusting again for age, sex and use of biologic agents showed that patients with SSc had increased mortality (OR: 6.90, 95% CI: 1.41 to 33.72), followed by SLE (OR: 4.05 95% CI: 0.96 to 17.12) and RA patients (OR: 3.65, 95% CI: 1.06 to 12.54), whereas PsA patients had comparable mortality risk with AS patients. Conclusion: Comparing to the general population, Covid-19 may have a more severe impact in real-world patients with systemic rheumatic disease. Covid-19 related mortality is increased in subgroups of patients with specific rheumatic diseases, especially in older ones, underscoring the need for priority vaccination policies and access to targeted treatments.

Gut dysbiosis associated with worse disease activity and physical function in axial spondyloarthritis.

BACKGROUND: Based on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut dysbiosis, intrinsic to IBD, has also been observed in axSpA. It is, however, not established to what degree gut dysbiosis is associated with axSpA disease severity. The objective of this study was to compare gut dysbiosis frequency between controls, non-radiographic axial spondyloarthritis (nr-axSpA), and ankylosing spondylitis (AS) patients and investigate whether gut dysbiosis is cross-sectionally associated with axSpA disease activity, physical function, mobility, or pain. METHODS: Gut dysbiosis was assessed by 16SrRNA analysis of feces from 44/88 nr-axSpA/AS patients (ASAS/mNY criteria) without inflammatory bowel disease (IBD) and 46 controls without IBD or rheumatic disease. The GA-map™ Dysbiosis Test was used, grading gut microbiota aberrations on a 1-5 scale, where ≥3 denotes dysbiosis. Proportions with dysbiosis were compared between the groups. Furthermore, standard axSpA measures of disease activity, function, mobility, and pain were compared between patients (nr-axSpA and AS combined) with and without dysbiosis, univariately, and adjusted for relevant confounders (ANCOVA). RESULTS: Gut dysbiosis was more frequent in AS than controls (36% versus 17%, p=0.023), while nr-axSpA (25% dysbiosis) did not differ significantly from either AS or controls. Univariately, most axSpA measures were significantly worse in patients with dysbiosis versus those without: ASDAS-CRP between-group difference 0.6 (95% CI 0.2-0.9); BASDAI 1.6 (0.8-2.4); evaluator's global disease activity assessment (Likert scale 0-4) 0.3 (0.1-0.5), BASFI 1.5 (0.6-2.4), and VAS pain (cm) 1.3 (0.4-2.2). Differences remained significant after adjustment for demographics, lifestyle factors, treatments, gut inflammation (fecal calprotectin ≥50 mg/kg), and gut symptoms, except for VAS pain. BASMI and CRP were not associated with dysbiosis. CONCLUSION: Gut dysbiosis, more frequent in AS patients than controls, is associated with worse axSpA disease activity and physical function, seemingly irrespective of both gut inflammation and treatments. This provides further evidence for an important link between disturbances in gastrointestinal homeostasis and axSpA.

Effects of Different Drug Therapies and COVID-19 mRNA Vaccination on Semen Quality in a Man with Ankylosing Spondylitis: A Case Report.

Background and Objectives: Ankylosing spondylitis (AS) is a condition that affects 0.1% to 0.5% of the adult population. The aim of this case report was to investigate the possible effects of the drugs taken for treatment of AS as well as mRNA vaccination for COVID-19 on semen quality by performing a highly detailed analysis. Materials and Methods: Sperm characteristics were examined by light microscopy, DNA fragmentation (DFI) was analysed by flow cytometry and morphology was evaluated by transmission electron microscopy (TEM). Results: Semen analysis under therapy with (1) celecoxib and sulphasalazine showed: concentration 47 million/mL, 53% progressive motility, 7% normal morphology and 9.6% DFI, (2) Golimumab and before mRNA Vaccination showed: concentration 108 million/mL, 82% progressive motility, 1% normal morphology and 7.6% DFI, and (3) Golimumab and after 3 doses of mRNA Vaccination showed: concentration 142 million/mL, 85% progressive motility, 1% normal morphology and 6.8% DFI. TEM revealed head, neck and tail abnormalities, as well as the presence of cells with incomplete spermiogenesis white cells and phagocytes in the sample under therapy with celecoxib and sulphasalazine. Golimumab treatment lead to an increased incidence of elongated heads but in general reduced inflammation as no white cells were evident in TEM. Conclusion: The anti-inflamatory drugs celecoxib and sulphasalazine had no adverse effect on sperm quality as all parameters were within normal limits and the patient achieved under that treatment 2 pregnancies following natural conception that lead to the birth of a healthy boy and girl respectively. Anti-TNFa treatment with Golimumab exerted a negative effect on morphology but not on concentration, motility and DFI. After 3 doses of mRNA Vaccination, sperm concentration increased while motility, morphology and DFI remained similar to the values before vaccination suggesting no negative effect of the mRNA vaccine for COVID-19 on sperm quality.