Axial spondylarthritis following COVID-19 infection.

Although SARS-CoV-2 syndrome primarily affects the lungs, systemic manifestations have been reported. New rheumatic immune-mediated inflammatory diseases have been reported following SARS-CoV-2 infection. We present a case of a woman in her mid-30s who developed inflammatory back pain due to bilateral sacroiliitis with erosions after contracting SARS-CoV-2 infection. Her inflammatory markers on presentation were normal. MRI of the sacroiliac joints demonstrated bone marrow oedema and erosive changes in both sacroiliac joints. As the patient was intolerant to non-steroidal anti-inflammatory drugs, adalimumab 40 mg subcutaneous (SC) injection was administered, which improved her symptoms in 8 weeks. However, due to the drug's side effects, SC adalimumab was switched to intravenous infliximab. The patient is currently tolerating her intravenous infliximab well and has experienced significant improvement in her symptoms. We reviewed the current literature on the prevalence of axial spondyloarthropathy after SARS-CoV-2 infection.

Prolonged peripheral seronegative spondyloarthritis following BioNTech coronavirus disease 2019 vaccination: A case report.

A female 17-year-old diagnosed with seronegative spondyloarthritis (SpA) following the first jab of the BioNTech162b2 (BNT162b2) vaccine presented with recurrent swelling and painful knee accompanied by posterior heel tenderness over the past 1.5 months. Laboratory investigations revealed elevated serum erythrocyte sedimentation rate and C-reactive protein. Synovial aspiration yielded level 3 crystal-free, aseptic and inflammatory effusion. She tested positive for the human leukocyte antigen-B27 and was diagnosed with peripheral SpA. She received daily celecoxib (400 mg), methylprednisolone (8 mg), and sulfasalazine (2 g), but the effect was limited. Nonetheless, her symptoms improved significantly with weekly subcutaneous etanercept administration (50 mg). Four weeks later, her arthritis was completely resolved. To our knowledge, this is the first case report of newly diagnosed seronegative peripheral SpA in an autoimmunity-disease-free individual following messenger RNA BNT coronavirus disease 2019 vaccination.

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.

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.

COVID-19 was not associated or trigger disease activity in spondylarthritis patients: ReumaCoV-Brasil cross-sectional data.

OBJECTIVES: To evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA). METHODS: ReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria. RESULTS: 353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62-8.47, p = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02-5.08, p = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33-24.9, p = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02-0.50, p = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41-53.64; p = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03-0.71; p = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02-0.76; p = 0.02) remained at final model as protective factor. CONCLUSIONS: Our results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments.

Do patients with rheumatoid arthritis show a different course of COVID-19 compared to patients with spondyloarthritis?

OBJECTIVES: Rheumatoid arthritis (RA) and spondyloarthritis (SpA) are the most common inflammatory rheumatic diseases (IRD). The aim of this study was to elucidate differences in the outcome of SARS-CoV-2 infection in RA- and SpA-patients. METHODS: Data from the German COVID-19 registry for IRD patients from 30th March to 16th November 2020 were analysed. 208 RA and SpA patients were included in the study, matched for gender and age. RESULTS: 104 SpA patients (40% patients with ankylosing spondylitis, 54% with psoriatic arthritis and 6% with enteropathic arthritis) were compared to 104 RA patients. For both groups, median age was 56 years. TNF-i treatment was reported in 45% of the SpA and in 19% of RA patients (p=0.001). Glucocorticoids were used in 13% of the SpA and in 40% of the RA patients (p=0.001). In both groups, the majority of the patients (97% SpA, 95% RA) recovered from COVID-19. Hospitalisation was needed in 16% of the SpA and in 30% of the RA patients (p=0.05), and oxygen treatment in 10% and 18% respectively (p=ns). Three versus six (p=ns) fatal courses were reported in the SpA versus the RA group. CONCLUSIONS: The study revealed that the hospitalisation rate during COVID-19 infection, but not the mortality, was significantly higher in RA as compared to SpA patients. This could be explained either by different treatment strategies or by different susceptibilities of the two diseases.

Importance of the second SARS-CoV-2 vaccination dose for achieving serological response in patients with rheumatoid arthritis and seronegative spondyloarthritis.

OBJECTIVES: To assess the kinetics of humoral response after the first and second dose of messenger RNA (mRNA) vaccines in patients with inflammatory joint diseases compared with healthy controls (HC). To analyse factors influencing the quantity of the immune response. METHODS: We enrolled patients with rheumatoid arthritis (RA) and seronegative spondyloarthritis (SpA), excluding those receiving B-cell depleting therapies and assessed the humoral response to mRNA vaccines after the first and the second dose of the vaccine in terms of seroconversion rate and titre. We compared the results to a HC group and analysed the influence of therapies as well as other characteristics on the humoral response. RESULTS: Samples from 53 patients with RA, 46 patients with SpA and 169 healthy participants were analysed. Seroconversion rates after the first immunisation were only 54% in patients with inflammatory arthritis compared with 98% in the HC group. However, seroconversion rates were 100% in all groups after second immunisation. Patients developed reduced antibody titres after the first vaccination compared with HC, but there was no difference after the second dose. While disease modifying anti-rheumatic drug (DMARD) monotherapy did not affect antibody levels, seroconversion rates as well as titre levels were reduced in patients receiving a combination of DMARDs compared with HC. CONCLUSIONS: Patients with inflammatory joint diseases under DMARD therapy show impaired humoral responses to the first vaccine dose but excellent final responses to vaccination with mRNA vaccines. Therefore, the full course of two immunisations is necessary for efficient vaccination responses in patients with inflammatory arthritis under DMARD therapy.

Axial spondyloarthritis may protect against poor outcomes in COVID-19: propensity score matched analysis of 9766 patients from a nationwide multi-centric research network.

INTRODUCTION: The outcomes of COVID-19 in patients with axial spondyloarthritis (ax-SpA) have not been explored in detail. Tumour necrosis factor inhibitors (TNFi) are commonly used for ax-SpA patients, and how they influence outcomes may have implications on COVID-19 management. METHODS: A nationwide multi-centric research network was queried for patients with ax-SpA, including ankylosing spondylitis (AS) and non-radiographic SpA (nr-SpA) who had developed COVID-19. An equal number of propensity score(PS) matched controls were extracted from the database amongst patients with COVID-19 who did not have any inflammatory arthritis. Outcomes included mortality and others including hospitalization, intensive care unit, ventilation, acute kidney injury (AKI), renal replacement therapy, acute respiratory distress syndrome, cerebral infarction, venous thromboembolism (VTE), and sepsis. RESULTS: We identified 9766 patients with ax-SpA (924 AS and 8842 nr-SpA) and 691,862 without SpA who had COVID-19. In the unmatched comparison, patients with ax-SpA had higher risk ratios (RR) for all outcomes. After matching for demographics and comorbidities, patients with ax-SpA had lower RR for mortality [RR: 0.707 (95% CI: 0.598-0.836), p < 0.0001], severe COVID-19 [RR: 0.791 (0.69-0.906), p = 0.0007], hospitalization [RR: 0.872 (0.826-0.921), p < 0.0001], and AKI [RR: 0.902 (0.816-0.997), p = 0.044]. Only the risk of VTE was higher in ax-SpA patients [RR: 1.219 (1.037-1.433), p = 0.016]. Amongst the ax-SpA group, males had worse outcomes in 9 out of the 11 domains except for VTE and cerebral infarction, while blacks had worse outcomes in all except for mortality and the need for renal replacement therapy. AS had similar risk ratios for all outcomes compared with nr-SpA except hospitalization [RR: 1.457 (1.03-2.06), p = 0.0318]. There was no difference in outcomes in patients who had received TNFi in the year previous to COVID-19 infection. Ax-SpA patients who had been prescribed non-steroidal anti-inflammatory drugs in the 3 months prior to COVID-19 had poorer outcomes. CONCLUSION: In conclusion, COVID-19 outcomes were better in patients with ax-SpA as compared with PS matched controls except for increased risk for VTE. The use of TNFi is not associated with better or worse outcomes. These apparently protective effects observed need to be validated and explored further. Key Points • Patients with axial spondyloarthritis have lower mortality and morbidity during COVID-19 infections as compared with propensity score matched controls. • Axial spondyloarthritis is associated with higher risks for venous thromboembolism during COVID-19. • There is no difference in outcomes between ankylosing spondylitis and non-radiographic spondyloarthritis except in rates of hospitalization, which were higher in ankylosing spondylitis. • Use of tumour necrosis factor inhibitors did not influence COVID-19 outcomes.

The Interplay Between COVID-19 and Spondyloarthritis or Its Treatment.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has created multiple uncertainties regarding rheumatic diseases or their treatment, with regard to the susceptibility to or severity of the viral disease. We aimed to address these questions as they relate to spondyloarthritis (SpA). METHODS: We created a longitudinal survey from April 10, 2020, to April 26, 2021. There were 4723 subjects with SpA and 450 household contacts who participated worldwide. Of these, 3064 respondents were from the US and 70.4% of them provided longitudinal data. To control for the duration of potential risk of COVID-19, the rate of contracting the disease was normalized for person-months of exposure. RESULTS: In an analysis of US subjects who provided longitudinal data, the incident rate ratio for the 159 (out of 2157) subjects who tested positive for COVID-19 was 1.16 compared to the US population as adjusted for age and sex (range 0.997-1.361, P = 0.06). A paired evaluation using patients and household members did not show a statistically significant effect to indicate a predisposition for developing COVID-19 as a result of SpA or its treatment. Our data failed to show that any class of medication commonly used to treat SpA significantly affected the risk of developing COVID-19 or increasing the severity of COVID-19. CONCLUSION: These data do not exclude a small increased risk of developing COVID-19 as a result of SpA, but the risk, if it exists, is low and not consistently demonstrated. The data should provide reassurance to patients and to rheumatologists about the risk that COVID-19 poses to patients with SpA.

Twenty years of clinical trials in axial spondyloarthritis: what can we learn for the future?

PURPOSE OF REVIEW: We have now about 20 years of experience with the treatment of axial spondyloarthritis with biologics, which raises the question what we can learn from past experience, and which open questions should be addressed in future investigations. RECENT FINDINGS: Many studies have shown that axSpA patients - both patients in their nonradiological and radiological stage - respond similarly well to biologic treatment and these patients should be seen as having the same disease at different stages. AxSpA respond best to TNF-blocker - and probably also to other biologics - if the disease duration is short and if objective parameters of inflammation, such as C-reactive protein or MRI are positive. Primary aim of treatment is to reach and maintain clinical remission. Once remission is achieved, it can be maintained by continuing treatment, and in a proportion of yet not well defined patients the drug dose can be reduced without inducing a flare. The recent demonstration of a good efficacy, in addition to TNF blockers, also of IL-17 inhibitors and JAK-inhibitors in axSpA patients raises the question how to select the best patients for the best treatment. Radiographic progression can best be stopped by effectively suppressing inflammation, whether different drugs have here a different effect has still to be defined. More sensitive measurements of radiographic progression are urgently needed. SUMMARY: Reaching and maintaining clinical remission and preventing structural bony damage is the primary treatment target in patients with axSpA. How to reach this aim best has to be further explored in the future.