ABSTRACT
Background: Upadacitinib (UPA) was shown to be safe and effective through 2 years in patients (pts) with active ankylosing spondylitis (AS) naïve to biologic disease-modifying antirheumatic drugs (bDMARDs) in the pivotal phase 2/3 SELECT-AXIS 1 trial.1,2 Objectives: To assess the efficacy and safety of UPA in pts with active AS with an inadequate response (IR) to bDMARDs. Methods: SELECT-AXIS 2 (NCT04169373) was conducted under a master protocol and includes two separate studies (one for AS bDMARD-IR and one for non-radiographic axial spondyloarthritis [nr-axSpA]). The AS bDMARD-IR study is a randomized, double-blind, placebo (PBO)-controlled, phase 3 trial that enrolled adults ≥18 years with AS who met modifed New York criteria, had BAS-DAI and pt's assessment of total back pain scores ≥4 (numeric rating scale 0-10) at study entry, and had an IR to one or two bDMARDs (TNF inhibitor or IL-17 inhibitor). Pts were randomized 1:1 to receive oral UPA 15 mg once daily (QD) or PBO during the 14-week (wk) double-blind treatment period. The primary endpoint was ASAS40 response at wk 14. Multiplicity-controlled secondary endpoints evaluated at wk 14 were improvements from baseline in disease activity (ASDAS [CRP], ASDAS ID [<1.3], ASDAS LDA [<2.1], BASDAI50, ASAS20, and ASAS PR), pain (total and nocturnal back pain), function (BASFI), objective measure of infammation (SPARCC MRI score of the spine), spinal mobility (BASMI), enthesitis (MASES), and quality of life (ASQoL and ASAS HI). Non-responder imputation incorporating multiple imputation (NRI-MI) was used to handle intercurrent events and missing data for binary endpoints. Cochran-Mantel-Haenszel (CMH) test and mixed-effect model for repeated measures (MMRM) were used for analyzing binary and continuous endpoints, respectively. Treatment-emergent adverse events (TEAEs) assessed through wk 14 are reported for pts who had ≥1 dose of study drug. Results: All 420 randomized pts with active AS received assigned treatment (UPA 15 mg, n=211;PBO, n=209);409 (97%) received study drug through wk 14. Baseline demographic and disease characteristics were generally similar between treatment groups and refective of an active AS bDMARD-IR population (74% male;mean age 42.4 years;mean disease duration 7. 7 years;83% HLA-B27 positive;mean BASDAI 6.8). Signifcantly more pts achieved the primary endpoint of ASAS40 response at wk 14 with UPA vs PBO (45% vs 18%;P<0.0001;Figure 1);UPA showed onset of effect in ASAS40 as early as wk 4 (nominal P≤0.05). All multiplicity-controlled secondary endpoints met statistical signifcance for UPA vs PBO at wk 14 across multiple clinical domains of AS (P<0.0001;Figure 1). The rate of TEAEs was similar between treatment groups through wk 14 (UPA, 41%;PBO, 37%). TEAEs led to discontinuation in 3 (1.4%) pts treated with PBO and none with UPA. Serious infections occurred with UPA (2.4%) but not with PBO and included 4 events of COVID-19 and 1 event of uveitis. Additional events of uveitis were reported in 3 (1.4%) pts treated with PBO. Infammatory bowel disease (IBD) occurred in 1 (0.5%) pt on UPA and none on PBO. No malignancy, major adverse cardiovascular events, venous thromboembolic events, or death were reported with UPA;1 event of malignancy was observed with PBO. Conclusion: UPA 15 mg QD was signifcantly more effective than PBO over 14 wks of treatment in pts with active AS and IR to bDMARDs. No new safety risks were identifed with UPA compared with its known safety profile.3,4 These fndings are consistent with and complementary to those of SELECT-AXIS 1 (bDMARD-naïve AS population),1,2 and support the use of UPA in pts with active AS, including those who had a previous IR to bDMARD therapy.
ABSTRACT
Background: Considering the concerns regarding COVID-19 vaccine safety among patients with rheumatic diseases due to a lack of data, an urgent need for studies evaluating safety profiles of vaccines emerged. Objectives: Vaccination against the coronavirus disease-2019 (COVID-19) started in March 2021 in the group using biological therapy in our country. In this study, post-vaccine real-life data of patients with spondyloarthritis (SpA) followed up with biological therapy were analyzed. Methods: Adult patients diagnosed with SpA who were followed up under biological therapy and vaccinated by CoronaVac inactive SARS-CoV-2 orBNT162b2 messenger RNA (mRNA) COVID-19 (Pfzer-BioNTech) vaccine were included in our observational, multicenter, prospective study. Results: A total of 287 patients (58.2% male;mean age: 47) were included in the study. 202 (%70,4) of patients were being followed up with the diagnosis of AS, 40 (%13,9) of them with PsA, 32 (%11,1) of them with nr-axSpA, 11 (%3,8) of them with enteropathic arthritis, and 2 (%0,7) of them with uSpA. The most common comorbidities were found to be HT (n:65;22.6%) and DM (n:38;13.2%). While 221 (77%) of the patients were receiving biological therapy alone, 27 (9.4%) patients were using methotrexate, 25 (8.7%) patients were using sul-fasalazine, and 12 (4.2%) patients were using lefunomide. The median duration of biological therapy was 40 weeks (19-75 IQR). The most commonly used treatment was infiximab (26.8%), adalimumab (23.3%) was the second (Table 1). It was determined that 207 (72.1%) of the patients preferred inactivated virus vaccine, while 80 (27.9%) preferred mRNA vaccine. When the time between the biological treatment and the day of vaccination is examined, detected median time between biological treatment and the frst dose of vaccination is 11.5 days (5-19 IQR), between the frst dose of vaccination and biological treatment is 14 days (7-21 IQR), between treatment and the second dose of vaccine is 14 days (5-23.5 IQR), and between the second dose of vaccine and the next biological treatment is 12.5 days (7-15 IQR). While 25 (8.7%) of the patients had COVID-19 infection before vaccination, 7 (2.4%) patients were found to have COVID-19 after vaccination (p<0.001). While two of the patients who had COVID-19 infection in the pre-vaccination period required hospitalization, none of the patients who had COVID-19 in the post-vaccination period required hospitalization. The rate of patients who developed side effects after the frst dose of the vaccine was 20.6%. The side effects seen, respectively, were detected as pain-redness at the injection site (16%), fatigue (11.8%), headache (8.4%), muscle-joint pain (7.3%) and fever (5.6%). The rate of patients reporting side effects after the second dose of the vaccine was 17.1%. The incidence of side effects after mRNA vaccine was found to be statistically signifcant compared to inactivated virus vaccine in terms of both doses (p=0.011, p<0.001). Major side effects such as myocarditis, ana-phylaxis-angioedema, myocardial infarction, and thrombosis were not observed in any of the patients included in the study. There was no evidence of disease activation in the median follow-up of 209 days (145-280 IQR) after vaccination. Conclusion: During the follow-up of the patients during the study, no major vaccine-related side effects, post-vaccine disease activation and the need for treatment change were not detected. In order to more accurately evaluate the efficacy of the vaccination program in the patient population using biologic agents, larger-scale studies including unvaccinated individuals are needed.
ABSTRACT
Background/Aims Psychological distress is prevalent in people with inflammatory arthritis. In populations with axial spondyloarthritis (SpA), the risk of developing mental ill-health is high - for depression more than twice that of control populations. Positive emotions are protective against psychological distress and emotional wellbeing is favourably associated with physical illness prognosis. However, the emotional experiences of people who live with axial SpA are not well understood. This study aimed to explore and synthesise qualitative data about the emotional experience of living with axial SpA and identify barriers and facilitators to emotional wellbeing. Methods First, a systematic review and thematic synthesis was conducted. Nine databases were searched from inception to December 2019. Qualitative and mixed methods studies were included if they reported qualitative participant level data about the lived emotional experiences of people with axial SpA and were published in English or German. The search was updated in March 2021. Study quality was assessed using a modified version of the CASP (Critical Appraisal Skills Programme) qualitative tool. Grey literature was appraised using the Authority, Accuracy, Coverage, Objectivity, Date, Significance (AACODS) checklist. Data were extracted, coded and categorised. Synthesis involved translation of concepts from one study into another and development of descriptive themes. Second, four axial SpA online forums were searched from inception to June 2020 for posts from UK-based individuals with axial SpA containing data about their emotional experiences of axial SpA. Thematic analysis was undertaken. Results Of 10,824 database records screened, 27 studies, published between 1995 and 2020, went forward for synthesis. Study populations included people diagnosed with Ankylosing Spondylitis (n=1143), axial SpA (n=53) and non-radiographic axial SpA (n=18). Two studies with mixed populations (n=37) did not specify numbers diagnosed with axial SpA. Most participants were male and had established disease. No studies specifically focused on the psychological experiences of living with axial SpA. 537 posts were identified from online fora, 278 (52%) of which were from men. Seven descriptive themes were generated from the qualitative synthesis: delayed diagnosis: a barrier to emotional wellbeing;disruptive symptoms: a source of mood swings;work disability: a loss of self-esteem;obstacles in interpersonal relationships: a trigger of distress;taking up exercise: 'personal pride' or 'unwelcomed reminders';anti-TNF therapy: hope reignited despite concerns;journey of acceptance: worry mixed with hope. The findings from our review of online fora supported and validated these themes. One additional theme - COVID-19: uncertainty and anxiety during the pandemic - was developed from constructs identified from online posts. Conclusion Our findings highlight substantial negative and mixed emotions experienced by people with axial SpA. However, data about the emotional experiences of women, people diagnosed with non-radiographic axial SpA, and those in the early stages of diagnosis, are limited.
ABSTRACT
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.
Subject(s)
Axial Spondyloarthritis , Spondylarthritis , Spondylitis, Ankylosing , Dysbiosis , Humans , Leukocyte L1 Antigen Complex , Spondylarthritis/diagnosis , Spondylitis, Ankylosing/diagnosisABSTRACT
BACKGROUND: Case report of a 21-year-old female developing non-radiographic axialspondyloarthritis in the setting of a preceding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We felt this was a unique case as some cases of psoriatic arthropathy and reactive arthropathy but none, to our knowledge of non-radiographic axial spondyloarthritis. CASE PRESENTATION: Twenty one-year-old female presented in June 2020 with inflammatory symptoms with general work-up per primary care provider being negative. Upon further work-up per Rheumatology, felt to have inflammatory back pain with X-rays of SI joints showing grade II sclerosis. Further work-up including magnetic resonance imaging was positive demonstrating bone edema and erosions of SI joint. This prompted further investigation and she had had some vague symptoms of SARS-CoV-2 several months prior including loss of smell, fatigue, and malaise. SARS-CoV-2 semiquanitative antibodies where done that where high positive. She was treated with cetrolizumab and had prompt improvement over the course of the next week. DISCUSSION AND CONCLUSION: Mechanism of SARS-CoV-2 triggering autoimmunity is still unknown at this time. However, it is important that insights be gained into the type of disease that can be triggered by this infection. As the pandemic continues to rage on, Rheumatologist need to be increasing aware that patients presenting with various forms of inflammatory arthritis may be triggered by an antecedent SARS-CoV-2 infection. Following these cases may help to determine how they differ from other forms of inflammatory arthropathy.