Current Prescribing Practices in Psoriatic Arthritis - Comparison between the Uk and Europe

Background/Aims Psoriatic arthritis (PsA) is a multi-system disease with a range of management options. Treatment may vary by geographic location. We compared disease characteristics and prescribing practices in the UK and Europe in the post-Covid era. Methods The ASSIST study was a cross-sectional observational study of PsA patients aged 18 years and older selected from 24 centres across 5 countries (UK, France, Germany, Italy and Spain) between July 2021 and March 2022 (IRAS: 287039). Patients attending a face-to-face appointment with a diagnosis of PsA made by a rheumatologist were selected by systematic sampling at each centre and treated in routine clinical practice. Patient and disease characteristics, current treatment and treatment decisions (medications unchanged, switched, added or reduced) were recorded. The analysis was descriptive, with no imputation of missing data. Results 503 patients were included, with arthritis subtype, patient age, disease activity and duration shown (Table 1). Physician- and patient-reported disease severity was highest in the UK, where median patient age was lowest. Conventional synthetic (cs) DMARDS constituted a higher percentage of current PsA treatment in UK than continental Europe (66.4% vs 44.9%), whereas biologic use was more frequent in Europe (68.1% vs 36.4%). Adalimumab was the most commonly used biologic in the UK and Spain. Adalimumab and secukinumab were equally used in Germany, and ixekizumab and adalimumab were joint-first in Italy. Implementing change to the current PsA treatment was most common in the UK, predominantly being a treatment increase. This may reflect the higher level of disease activity or younger patient age in the UK than other countries, as treatment escalation is more likely earlier in the disease course. In the UK, treatment escalation was more commonly achieved by medication addition (26.2%) than medication switch (14%) or dose increase (7.5%). In Europe, medication addition and switch were of more similar frequency (10.9% vs 9.85%). Conclusion Disease characteristics and treatment strategies varied between countries, but particularly between UK and the rest of Europe. In contrast to mainland Europe, csDMARDs predominated in the UK, perhaps reflecting current NICE guidelines. Treatment escalation was most common in the UK, in keeping with higher disease activity. (Table Presented).

Bimekizumab efficacy and safety in patients with moderate to severe plaque psoriasis: two-year interim results from the open-label extension of the randomized BE RADIANT phase 3b trial.

BACKGROUND: Bimekizumab is a monoclonal IgG1 antibody that inhibits interleukin (IL)-17A/F. Bimekizumab is more efficacious than secukinumab over one year in the treatment of psoriasis. OBJECTIVE: Evaluate safety and efficacy of bimekizumab through two years in patients with moderate to severe plaque psoriasis. METHODS: The BE RADIANT phase 3b randomized controlled trial consisted of a 48-week double-blinded period, where patients received bimekizumab (320mg every 4 or 8 weeks) or secukinumab (300mg weekly to Week 4, then every 4 weeks), and an open-label extension (OLE). From Week 48, all patients received bimekizumab in the OLE. RESULTS: At Week 48, more patients achieved complete skin clearance (PASI100; modified non-responder imputation) with bimekizumab than secukinumab (74.8% vs 52.8%). PASI100 responses were maintained to Week 96 in continuous bimekizumab patients (70.8%); patients who switched from secukinumab to bimekizumab had increased rates at Week 96 (76.6%). The most common adverse events were: nasopharyngitis, oral candidiasis, urinary tract infection. Safety data were consistent with the known safety profile of bimekizumab. LIMITATIONS: Limited racial diversity; overlap with COVID-19 pandemic. CONCLUSIONS: High PASI100 responses achieved with bimekizumab over 48 weeks were sustained through Week 96; secukinumab patients who switched to bimekizumab achieved similar response by Week 96.

Secukinumab treatment results in sustained drug survival in biologic-naive and biologic-experienced patients with moderate-to-severe plaque psoriasis: analysis of 24 months of follow-up data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)

Secukinumab is a fully human anti-interleukin-17A monoclonal antibody for the treatment of moderate-to-severe plaque psoriasis. In a previous analysis of the ongoing, longitudinal pharmacovigilance register BADBIR (data cutoff 31 August 2020), secukinumab showed sustained drug survival over 24 months in biologic-naive patients (86%) comparable to that of biologic-naive patients treated with ustekinumab (84%) and greater than that of biologic-naive patients treated with adalimumab (71%). In this updated analysis, we report drug survival for a larger cohort of biologic-naive and biologic-experienced patients with psoriasis treated with secukinumab (- data cutoff 31 August 2021). Patients prescribed secukinumab at baseline (biologic-naive) or after switching therapies during follow-up (biologic-experienced) were included. Drug survival up to 24 months (Kaplan-Meier method) was defined as the duration between date of first secukinumab exposure and date of stopping secukinumab or the end of the study censoring period. Data from 2850 patients were analysed (949 biologicnaive;1901 biologic-experienced). Mean duration of followup was 2.9 years (median 2.9 years) for biologic-naive and 2.7 years (median 2.5 years) for biologic-experienced patients. Among biologic-naive and biologic-experienced patients, respectively, most were male (61.3% and 55.6%), mean age was 46.5 and 45.1 years, mean body mass index was 31.6 and 32.5 kg m-2, mean age of disease onset was 25.6 and 23.7 years, and mean disease duration was 20.9 and 21.4 years. For biologic-experienced patients, the mean (SD) number of prior biologics received was 1.8 (1.0). Fewer biologicnaive patients had psoriatic arthritis (21.2% vs. 33.2%) and had received prior ciclosporin (50.1% vs. 60.1%), and prior methotrexate use was similar between subgroups (74.3% vs. 76.8%). Overall drug survival for biologic-naive and biologicexperienced patients was comparably high after 12 months (89% vs. 78%) and 24 months (78% vs. 62%). Drug survival for biologic-experienced patients was similar to that previously reported [77% (12 months) and 59% (24 months)]. With a median follow-up of 2.9 and 2.5 years for biologic-naive and biologic-experienced patients, respectively, these data represent the longest follow-up of any BADBIR analysis to date supporting and extending previous findings of sustained drug survival of secukinumab in patients with moderate-to-severe plaque psoriasis in real-world practice. As expected, drug survival was higher in patients who initiated secukinumab at baseline than those who switched to secukinumab after other biological therapy. However, overall drug survival of 78% and 62% at 12 and 24 months in biologic-experienced patients was similar to that reported previously [77% (12 months) and 59% (24 months)], and just slightly lower than was reported before the COVID-19 pandemic [81% (12 months) and 63% (24 months)].

Comparison Of The Efficacy And Safety Of Secukinumab, Ustekinumab And Guselkumab For The Treatment Of Moderate To Severe Plaque Psoriasis: A Systematic Review

Psoriasis is a chronic inflammatory skin condition characterized by scaly erythematous patches or plaques affecting the extensor surfaces that are prominent but spreading to all areas of the body, including the flexor surfaces. Psoriasis occurs when the body's immune system attacks the skin;the interleukin (IL)-12 and IL-17/23 axes play a major role in its pathogenesis. Biologic therapies targeting IL-17 or IL-23 have emerged as an important treatment option for psoriasis and have led to substantial improvements in patients' quality of life. This systematic review aimed to evaluate the comparative efficacy and safety of secukinumab, ustekinumab and guselkumab for the treatment of moderate to severe plaque psoriasis. Based on the final analysis, there were 10 articles, namely 5 RCTs and 5 observational. We found that patients who were given secukinumab showed a rapid response, whereas guselkumab was superior in terms of long-term response (approximately 1 year) and complete remission compared to other biologics. Among all the biologics assessed, ustekinumab showed relatively low efficacy.

Adalimumab, Ustekinumab, and Secukinumab in the Management of Hidradenitis Suppurativa: A Review of the Real-Life Experience.

To date, adalimumab (ADA) is the only biotechnology drug approved for the management of hidradenitis suppurativa (HS), an inflammatory skin condition. However, it quickly became apparent that the efficacy of adalimumab in daily practice was highly variable. In our review, we highlighted the current evidence from literature on the use of biologics in HS in a real-life setting, particularly adalimumab, secukinumab and ustekinumab. Data on the effectiveness and safety of biologic drugs in HS management have been analyzed. Even if the results are promising, more studies are needed. In our opinion, the armamentarium of drugs for HS management is increasing, and treatment will be based on a tailored-tail approach, minimizing the risk of adverse events. In this context, we want to point out the reported effectiveness and safety data concerning adalimumab, ustekinumab and secukinumab as well as ixekizumab.

Toxicity signals associated with secukinumab: A pharmacovigilance study based on the United States Food and Drug Administration Adverse Event Reporting System database.

AIMS: Secukinumab, the first interleukin 17A inhibitor, is widely used to treat immune diseases, including plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. Recently, many studies have reported adverse events associated with secukinumab, including gastrointestinal disorders, infections and infestations, and hypersensitive and nervous system disorders. OBJECTIVE: Here, we aimed to explore the clinical characteristics, outcomes and time to onset of the four main toxicities of secukinumab using post-marketing data. METHODS: Our study utilized data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2015 to 2021, using disproportionality analysis. Toxicities were defined based on the standardized Medical Dictionary for Regulatory Activities queries. Two disproportionality methods were used to detect potential signals: information component (IC) and reporting odds ratio (ROR). The signals were defined as ROR025 > 1 and IC025 > 0. RESULTS: A total of 73 945 398 records were included in this study, of which 300 665 records were related to secukinumab. Diarrhoea (N = 3538), nasopharyngitis (N = 3458), pruritus (N = 4277) and rash (N = 3270) were the most common adverse events. Inflammatory bowel disease (IC025 /ROR025 = 3.25/9.69), genital candidiasis (IC025 /ROR025 = 3.46/11.54), dermatitis psoriasiform (IC025 /ROR025 = 1.94/4.04) and anosmia (IC025 /ROR025 = 1.62/3.17) had the highest IC025 values of all toxicities. The time to onset of the four toxicities was mainly concentrated in the first month. Some patients simultaneously presented with two or more toxicities. CONCLUSION: This pharmacovigilance study systematically explored the four main toxicities of secukinumab and provided new safety signals based on past safety information. Some high-risk signals need to be given attention.

Interleukin-17 Inhibitor in Treatment of Psoriasis during COVID-19 Pandemic: An Ambispective Study

Introduction: Psoriasis is a genetically mediated chronic inflammatory disease that is frequently associated with metabolic co-morbidities. These metabolic co-morbidities have a huge impact in deciding the appropriate immunosupressant of choice in the current scenario of Coronavirus Disease (COVID-19) pandemic. Treatment of psoriasis especially with biologicals is challenging during covid pandemic since immunosuppressive therapy might interfere with antiviral immunity. Aim(s): To report the safety profile of Interleukin-17 (IL-17) inhibitor, namely injection secukinumab in patients of psoriasis vulgaris during COVID-19 pandemic. Material(s) and Method(s): An ambispective interventional study was performed on 23 patients of psoriasis who were administered secukinumab at a dose of 300 mg subcutaneously during COVID-19 pandemic.The study was conducted at the Department of Dermatology, Madras Medical College, Chennai, Tamil Nadu, India among the patients attending the psoriasis clinic between the July 2021 to March 2022. The demographic characteristics of the study group, previous treatment for psoriasis and the relationship between risk of COVID-19 infection and secukinumab were noted. Efficacy of secukinumab was calculated using Psoriasis Area and Severity Index (PASI) scores. Statistical analysis was conducted with Statistical Package for Social Sciences (SPSS) statistics software version 21.0 by Fischer's-exact test. Result(s): Out of 23 patients, 17 patients (11 males, six females) completed full course of nine doses (five weekly doses followed by four monthly doses) of secukinumab. The PASI 75 and PASI 90 were achieved in 9 (52.94%) and 8 (29.41%) patients respectively at the end of 12 weeks. None of the patients developed COVID-19 infection during the course of treatment and three months following therapy. Patients with psoriasis who had a history of COVID-19 infection did not show signs of reinfection when started on secukinumab. Both inactivated vaccine (Covaxin) and vector based vaccine (Covishield) were found to be safe in concomitant use with secukinumab. Conclusion(s): Secukinumab is found to be safe and effective in psoriasis treatment during COVID-19 pandemic. There is no increased risk of COVID-19 infection or reinfection, COVID-19 associated hospitalisation and mortality among patients with psoriasis administered with secukinumab. The drug can also be safely used with COVID-19 vaccines. Copyright © 2023 Journal of Clinical and Diagnostic Research. All rights reserved.

Immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients receiving secukinumab: a literature review.

Purpose: There is a paucity of evidence on the impact of immune-mediated inflammatory disease (IMID) treatments on the immunogenicity of SARS-CoV-2 vaccination. The purpose of this literature review is to address the question of whether patients with IMIDs receiving secukinumab, a fully human anti-interleukin-17A monoclonal antibody, have an adequate immune response after SARS-CoV-2 vaccination. Materials and Methods: Clinical studies that evaluated the effect of secukinumab on immune responses in patients with IMIDs after SARS-CoV-2 vaccination were searched in publication databases, including Medline and Embase, until May 2022. Results: From the 53 articles identified, a total of 11 articles were included. Overall, the majority of the patients treated with secukinumab elicited an adequate immune response to SARS-CoV-2 vaccines. Patients receiving secukinumab for IMIDs developed cellular immune responses following vaccination with the BNT162b2 vaccine, and there were no significant differences in the overall humoral and cellular immune responses between patients and healthy individuals. The third dose of the BNT162b2 mRNA vaccine resulted in a positive antibody response in secukinumab-treated patients. Conclusion: The available data provide no evidence of impairment in immunological response to SARS-CoV-2 vaccines by secukinumab in patients with IMIDs.

Challenges of COVID-19 in Rheumatic Autoimmune Diseases (RADs) Patients

Upon COVID-19 infection, age-specific mortality rates in RADs patients notably began from 35 years old, while in the uninfected population, it was from 55. COVID-19 associated rheumatic signs and symptoms are myalgia, fatigue, Kawasaki-like signs, and skin rashes mimicking vasculitides and pernio (chilblains) like lesions. So a variety of rheumatic diseases may mimic or be mimicked by COVID-19. Rheumatologic Treatments During COVID-19 Epidemic: Prednisone caused an increased hospitalization rate, significantly when the dose exceeded 10 mg per day. It is reasonable to reduce glucocorticoids gradually to 5 - 7.5 mg/day, but discontinuation during the pandemic is not recommended. Conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) reduce the risk of COVID-19 infection and the cytokine storm emerging in severe cases. Colchicine has reduced the mortality of COVID- 19 patients and the number of severe cases. Tapering or even discontinuing csDMARDs is suggested to recover immunity in severe cases, which may help rapidly eliminate the virus. Hydroxychloroquine is likely to increase survival in SLE patients, and it is not advisable to be discarded. Biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) may help reduce inflammatory cytokine storm under COVID-19 attack. Compared with RADs patients treated with CD20 monoclonal antibody rituximab or IL-17A antagonist secukinumab, patients receiving tumor necrosis factor (TNF) inhibitors etanercept and alemtuzumab or IL- 6 receptor antagonist tocilizumab may experience milder course. Applicable Laboratory Indicators: Elevation of ESR, CRP, ferritin, interleukin 6, and creatine kinase can be seen in COVID-19 and various rheumatic diseases. RADs related autoantibodies may present among non-RAD severe COVID- 19 cases. COVID-19 as a Risk Factor for Rheumatologic Diseases: Cases of Small vessel cardiac vasculitis/endothelium, immunoglobulin A (IgA) vasculitis in patients with Crohn disease, cutaneous vasculitis-like lesions, systemic arterial and venous thromboembolism including cryptogenic strokes and other vasculopathy features, systemic rheumatic diseases such as SLE, inflammatory arthritis, GCA, inflammatory myopathies, APS, Sjogren's syndrome, ANCA-associated vasculitides, seropositive rheumatoid arthritis, and Virus-associated or reactive arthritis and Crystal-related arthritis due to gout or calcium pyrophosphate disease has been reported. COVID-19, in the acute phase, may cause cytokine storm and severe inflammatory response;and in the chronic phase, patients become susceptible to autoinflammatory and autoimmune diseases. If a patient has signs and symptoms of rheumatic diseases after developing COVID-19, do not attribute these complaints entirely to COVID-19;consider starting a real dangerous rheumatic disorder.

Adaptations in the PURE registry in response to the COVID 19 pandemic: The impact of well-designed modifications in real-world data collection in a psoriasis registry

Introduction: PURE is an international registry of adult patients with moderate-to-severe psoriasis treated with secukinumab (Cohort 1) vs other approved therapies (Cohort 2). The SARS-CoV-2 (COVID-19) pandemic necessitated adaptations in the collection of data enabling continued, successful monitoring of patients in the registry. This presents an overview of these changes and their impact on the PURE registry. Materials and methods: This ongoing registry enrolled 2362 adult patients with moderate to severe psoriasis (1:1 ratio;secukinumab: other treatments) from 81 community and hospital sites. As a noninterventional study, PURE registry allowed for flexibility in the visit schedule and type of visit (remote visits vs face-to-face) per routine practice. This enabled monitoring of patient outcomes during the pandemic at sites where appropriate resources and capabilities were available to perform virtual visits (video teleconferencing, or through phone calls with photographs). The video conference/photographs should have ensured that the investigator was able to assess the disease activity and its extent. The eCRF was modified to record the type of visit (Remote or On-site) and COVID-19 related adverse events (AE). This included diagnostic testing, symptoms, and concomitant medications. Clear definitions for suspected/confirmed and symptomatic/asymptomatic COVID-19 diagnoses, and the associated data entry instructions with clear illustrative examples were provided. COVID-19 related outcomes are being reported separately at this congress. Conclusions: Adaptations to PURE registry successfully enabled continued follow-up of psoriasis patients through the COVID-19 pandemic. The COVID-19 AE data provides us with the opportunity to explore the impact of the pandemic on patients with psoriasis treated with secukinumab.

COVID19 VACCINATION in PATIENTS with AXIAL and PERIPHERAL SPONDYLOARTHRITIS and PSORIATIC ARTHRITIS: ADVERSE EVENTS and IMPACT on DISEASE ACTIVITY

Background: There is scarce evidence on the rate of adverse events and the consequences on disease activity after vaccination against covid19 Objectives: To evaluate adverse events to vaccination and disease fares after vaccination in patients with axial spondyloarthritis (axSpA), peripheral spondy-loarthritis (pSpA) and psoriatic arthritis (PsA) and to evaluate factors associated with adverse event. Methods: Cross-sectional, observational, descriptive study. Consecutive patients with diagnosis of ankylosing spondylitis (AS) and non-radiographic axial spondy-loarthritis (nr-axSpA) according to ASAS 2009 criteria;pSpA according to ASAS 2011 criteria and PsA according to CASPAR criteria were included. Demographic data, disease clinimetry, treatments, vaccination received and post-vaccination adverse events were recorded. We evaluated, according to medical criteria, whether the patient presented a fare disease after vaccination and whether it was mild, moderate or severe. We also evaluated the factors associated with the presence of at least one mild adverse event. Statistical analysis: descriptive statistics were performed, qualitative variables were expressed as frequency and percentage (%), numerical variables as mean and standard deviation (SD) or median and percentile25-75. Binary logistic regression was performed using the presence of at least one mild adverse event to vaccination as the dependent variable. Results: 210 patients were included with a mean age of 45 (SD 15) years. The diagnoses were: AS 50 (23.8%), nr-axSpA 10 (4.8), pSpA 9 (4.3%), PsA 141 (67%) and time of disease evolution in months 109 (SD 96). Regarding comorbidities, the following frequencies were reported: arterial hypertension 60 (30%), diabetes mellitus 25 (12%), heart failure 4 (2%), asthma/EPOC 15 (7%), infammatory bowel disease 2 (1%), acute anterior uveitis 20 (9.5%), psoriasis 128 (61%). Sixteen percent (n=33) of the patients had SARS-CoV-2 infection prior to vaccination. Regarding treatments, those used were: antiTNF 88 (42%), Tofacitinib 6 (2.9%), Ustekinumab 2 (1%), Secukinumab 35 (17%), Ixekizumab 2 (1%), methotrexate 98 (47%), lefunomide 7 (3. 3), sulfasalazine 7 (3.3), apremilast 1 (0.5%), continuous NSAIDs 26 (12.4%) and NSAIDs on demand 103 (49%). Vaccines received were: Sputnik V 109 (51.9%), Oxford Vaccine, AstraZeneca 63 (30%), Janssen 1 (0.5%), BioNTech Vaccine, Pfzer 1 (0.5%), Sinopharm 33 (15.7%), Moderna 0%, Novavax 0% and others;3 (1.4%). Thirty-eight percent (n=80) of patients reported having mild post-vaccination symptoms, of which 3.75% did not resolve, 41% resolved with medication and 39% resolved ad integrum without medication. The presence of mild adverse event to the vaccine was associated with lower use of methotrexate (31% vs 56 %, p<0.001), and lower age (54 (SD 14) vs 47 (SD 12), p<0.001), and lower BMI (25 (24-30.5) vs 28 (25-31), p<0.001);while no association was found with sex, diagnosis, comorbidities, treatments, desease activity or vaccines. In the logistic regression analysis all the variables remained independently associated with a lower probability of presenting a mild adverse event: methotrexate: OR: 0.30, 95%CI 0.15-0.58, p<0.001, age: OR: 0.97, 95%CI 0.95-0.99, p: 0.03, BMI: OR: 0.92, 95%CI 0.95-0.99, p: 0.02. Sixty-one percent (n=129) of patients received the 2nd dose of vaccination, which 27% (n=35) presented mild adverse event and only 1 (0.8%) patient suffered post vaccination disease fare. Conclusion: Vaccination against COVID19 appears to be safe in this population, with only mild adverse events and low frequency of fare disease. Mild adverse events were associated with less use of methotrexate, younger age and lower BMI.

CLINICAL and SEROLOGICAL EVOLUTION of RHEUMATIC PATIENTS INFECTED by SARS-COV-2

Background: SARS-CoV-2 infection is a public health problem due to its high contagiousness and mortality. Spectrum of symptoms ranges from no symptoms to interstitial pneumonia. Patients with rheumatic disease present an increased infectious risk, especially those treated with immunosuppressants or biologic therapy. Since the beginning of the pandemic, risk of contagion and development of complications in these patients has been questioned. Objectives: To describe hospitalization prevalence, seroconversion, and symptoms in patients under follow-up by the rheumatology department of a tertiary hospital. Methods: Observational, cross-sectional study conducted by phone interview including patients with different diagnosis of rhematic diseases. Data about symptoms, hospital admission, serology by ELISA (when >15 days of evolution), diagnosis and baseline treatment, from March 2020 to February 2021 were collected. Results: Eighty-six patients with different rheumatic diseases and positive COVID-19 PCR were included (82.35% women) in Table 1. Mean age was 49.30 years (16.16). The 48.71% received biological therapy, JAK inhibitors or apremi-last, with a median of 3.11 years (Q1 1,08;Q3 3,17). Secukinumab was the biological therapy most often used (24,32%), followed by Tocilizumab (13,51%). The 34,18% received DMARDs or immunosuppressors, with a median of 5.09 years (Q1 12,25;Q3 11.09). The most frequent symptoms were asthenia (72.15%), headache (66.23%) and cough (59.49%). Nine patients (11.25%) were admitted to hospital, eight of them (10%) for pneumonia. Three of them were admitted to intensive care and one died. Seroconversion occurred in 53.25%. low IgG titers were present in 2.94% and IgM persisted positive in 56.25% of this group. In 6.45% the result was indeterminate. Conclusion: Hospitalization and mortality rate obtained was low and the most frequent symptoms were mild. Seroconversion occurred in more than 50% of patients and the result of 6.45% was indeterminate. It's important to highlight that since March 2020 to May 2020 IgG positive prevalence was 25%, while since September 2021 to February 2021, this prevalence increased until 57,45%. This difference is due to a modifcation of autoantibody detection technique since summer 2020.

LONGITUDINAL FOLLOW-UP of HUMORAL RESPONSE AGAINST SARS-COV-2 and VIRAL PERSISTENCE in 96 DMARDS-TREATED PATIENTS with PREVIOUS COVID-19 INFECTION

Background: Although it prevents severe forms of the disease, vaccination does not completely protect against the occurrence of COVID19 disease. If, DMARDs used have been associated with variable humoral response to SARS-CoV-2 vaccination, the impact of their use after SARS-CoV-2 natural infection have been poorly studied. Objectives: To characterize humoral response after SARS-CoV-2 infection and viral persistence in the nasopharyngeal sphere (NP), stools and blood of patients with rheumatic disease under DMARDs, and compared to healthy controls. Methods: Prospective monocentric longitudinal study including patients with rheumatoid arthritis or spondyloarthritis under DMARDs and with a confrmed SARS-CoV-2 infection (positive NP PCR and/or positive serology and/or pathognomonic thoracic tomography (CT)) during the frst or second wave of the COVID pandemic. Patients were followed up until one year after infection and humoral response was assessed before vaccination. Serum IgG and IgA antibodies against spike (S) and nucleocapsid (N) proteins were measured at every visit. Viral persistence was assessed at the early visit in the NP and stools using conventional RT-PCR and in the blood using a high sensitive technique (droplet digital PCR). Results: Between June 2020 and July 2021, we include 96 patients (50 SpA and 46 RA) with a mean age of 53 +/-14 years and 20 healthy controls (mean age 49 ± 16 years) corresponding to relatives of patients (spouses, children) living together and infected at the same time. The immune responses were analyzed according to 6 treatment groups: methotrexate (MTX)/salazopyrine (SLZ) monotherapy (n=17/2);anti-TNF monotherapy (n=24), anti-TNF + MTX (n=23);rituximab (RTX) (n=11);anti-IL17 or-23 (n=8);others (n=11). Visits were made at 1 month (29 ±13 days;n=18), 3 months (110 ±23 days;n=67), 6 months (231 ±35 days;n=48) and 12 months (368 ± 19 days;n=19) after infection. The anti-S and anti-N IgG Ab titers were not signifcantly different in the 6 treatment groups and the control population at 3 months. A signifcant decrease in anti-S IgA Ab titers was noted in the group treated with RTX (p=0.007) and with molecules targeting the IL17/23 pathway (p=0.007). A similar but non-signifcant trend was observed in these same treatment groups for anti-N IgA Ab (p=0.07). The titers of anti-SARS-CoV-2 antibodies at M3, was not associated with a severe COVID disease. Detection of SARS-Cov-2 RNA in stools and serum was negative for all samples taken at 1 month or 3 months. 4 patients (2 RA treated with abatacept/RTX and 2 SpA treated with anti-TNF/secukinumab) had a positive RT-PCR NP with low to very low viral load at the 1-month visit (mean Ct 36). None of these 4 patients had had a severe form of COVID19 infection. Conclusion: DMARDs-treated patients with previous proven COVID-19 did not seem to alter IgG Ab response but RTX and anti-IL17/-IL-23 might alter IgA humoral response. This lower immune response was not associated with a more severe disease. In these patients, new infection may not be considered as a full boost for the immune system. DMARDs did not induce viral persistence in the serum, the NP or in the stool.

THE EFFECT of SECUKINUMAB on the HUMORAL RESPONSE FOLLOWING TWO and THREE DOSES of the BNT162B2 MRNA VACCINE in PATIENTS with SPONDYLOARTHRITIS

Background: Data on the effect of secukinumab on the humoral response to the BNT162b2 mRNA vaccine are limited. Objectives: We aimed to assess prospectively the humoral response to the BNT162b2 mRNA vaccine in patients with spondyloarthritis (SpA) treated with secukinumab in comparison to immunocompetent controls. Methods: Patients with psoriatic arthritis (PsA) or ankylosing spondylitis (AS) treated with secukinumab for at least 3 months and immunocompetent controls were vaccinated with two-dose regimen of the BNT162b2 mRNA vaccine. Clinical and laboratory assessments were performed at 2-8 weeks [SpA: 37 on secukinumab, (median age 53% female), 122 controls (median age 53, 51% female)], and 6 months [SpA: 27 on secukinumab, 116 controls] after the second vaccine dose. A subgroup of patients (22 SpA on secukinumab, 45 controls) were evaluated after the third vaccine dose. The seropositive response was defned as a detectable S1/S2 IgG ≥15 binding antibody units (BAU)/ml. Results: The two-dose vaccine regimen induced a similar immunogenic response in patients and controls refected by the seropositivity rates of 100% in both groups. After six months, the rate of seropositivity remained as high as 96% in both secukinumab-treated patients and immunocompetent controls. The decline of S1/S2 IgG titer within six months was similar in controls and secukinumab-treated patients,-66.4 (95% CI {-70.9,-39.9}) and-55 BAU/ml (95% CI {-95.42,-36.87)). Following the third vaccine, the seropositivity rate increased to 100 % in both groups. At all-time points, S1/S2 IgG titers were similar in secukinumab treated patients and immunocompetent controls (Figure 1). Conclusion: SpA patients treated with secukinumab consistently demonstrated an adequate humoral response to the BNT162b2 mRNA vaccination similar to immunocompetent controls, both short-term and within six months after two vaccine doses and after the third vaccine dose.

FEATURES of the COURSE of COVID-19 in ELDERLY PATIENTS with IMMUNO-INFLAMMATORY RHEUMATIC DISEASES (PRELIMINARY DATA)

Background: It is assumed that patients with immuno-infammatory rheumatic diseases (IIRDs) in old age are susceptible to a more severe course of COVID-19 both due immunological disorders (autoimmune disease and its activity, immuno-suppressive therapy, immunosenescence leading to systemic subclinical chronic infammation with increased secretion of IL-6, IL-1, IL-18, TNF-α) and due to the presence of comorbid pathology. There are no Russian data on the course of COVID-19 in elderly patients with IIRDs. Objectives: To study the features of the course of COVID-19 in elderly patients with IIRDs. Methods: The study included 93 patients with IIRDs: 72 women, 21 men, average age 67.5±6.1 years. Of them, 62 patients suffered from rheumatoid arthritis, 9-systemic sclerosis, 5-ankylosing spondylitis, 4-Sjogren's disease, 4-systemic vasculitis, 3-psoriatic arthritis, 2-osteoarthritis, 1 systemic lupus erythematosus, 1-polymyositis, 1-rheumatic polymyal-gia, 1-gout. At the moment of COVID-19, 10 patients had high activity of IIRDs, 26-moderate, 40-low, 17-remission. 69 patients were treated with disease-modifying antirheumatic drugs-DMARDs (40-methotrexate, 12-lefunomide, 8-sulfasalazine, 7-hydroxychloroquine), 45-glucocorticoids (34-low doses, 11-medium or high doses). 36 patients received biologic or target DMARDs: 24-rituximab (the interval from the last administration to the development of COVID-19 symptoms averaged 7 months), 4-TNF-α inhibitors, 3-abatacept, 2-secukinumab, 1-tofacitinib, 1-baricitinib, 1 ustekinumab. Comorbidities included hypertension (n=74), coronary artery disease (n=27), obesity (n=17), diabetes mellitus (n=8), bronchial asthma (n=5), chronic obstructive pulmonary disease (n=4), chronic kidney disease (n=3). The patients were interviewed by a research doctor, additional information was obtained from medical documentation. Results: The most common symptoms of COVID-19 were fever-67.7%, weakness/drowsiness-53.7%, cough-48.4%, as well as anosmia and dyspnea-35.5% each, headache-20.4%, body aches-16.1%, congestion nose-8.6%, chest pain-7.5%, dysgeusia-5.4%, diarrhea/vomiting-3.2%. According to CT chest scan, 8 patients had 0% of lung damage, 31-25%, 32-50%, 12-75%, in other cases the study was not carried out (n=9) or data are not available (n=1). In 2 patients the course of COVID-19 was complicated by bacterial pneumonia, in 1-bacterial-fungal. An asymptomatic course was noted only in 2 patients (PCR+/IgM +, CT 0, close contact with a confrmed case of COVID-19). Recovery was noted in 90 patients, fatal outcome-in 3. Exacerbation of IIRDs after COVID-19 was noted in 48.4% of patients, which required intensifying antirheu-matic therapy. Conclusion: Preliminary data indicate that COVID-19 is characterized by moderate and severe course in elderly patients with IIRDs. Further studies are required to identify risk factors for severe course and complications in order to provide timely qualifed care.

IMPACT of SARS-COV-2 INFECTION on the DISEASE ACTIVITY of PATIENTS with PSORIATIC ARTHRITIS under BDMARDS: REAL LIFE DATA

Background: SARS-CoV-2 infection can lead to severe infammation and has been suggested to induce Psoriatic Arthritis (PsA) fares.1 However, the impact on disease activity and response to biological disease modifying anti-rheumatic drugs DMARDs (bDMARDs) remains unknown. Objectives: To evaluate the effect of SARS-CoV-2 infection on disease activity and bDMARDs responses in patients with PsA. Methods: We performed a retrospective analysis including all the patients with PsA, meeting the CASPAR criteria and under biologic therapy, followed in the Rheumatology department of a tertiary university hospital. Demographic and clinical data, including occurrence of SARS-CoV-2 infection, were collected from our national database (reuma.pt). Disease activity (CDAI, SDAI, DAS28 4v, BASDAI, ASDAS) and bDMARDs responses (EULAR, ASDAS, ASAS, ACR and PsARC responses) were evaluated before and after SARS-Cov-2 infection. Statistical analysis was performed with SPSS. Continuous variables were compared through paired samples t-test. Results: A total of 102 patients with PsA were included. Fifty-two were females (51%).The mean age was 53 ± 11.09 years and the median disease duration was 15 years [min 2, max 47]. Overall, 54 (53%) patients had predominant axial involvement, 26 (26%) peripheric and 36 (37%) enthesopathic. The most used bDMARD was etanercept (n=28, 27.5%) followed by adalimumab (n=22, 21.6%) and secukinumab (n=18, 17.6%). The prevalence of SARS-CoV-2 infection was 15.7% (n=16). Sixty-three per cent received the BNT162b2 (Pfzer/BioNtech) vaccine, 31% received mRNA-1273 (Moderna), 13% received AZD1222 (AstraZeneca) and 13% received AD26. COV2.S (Janssen/Johnson & Johnson). Sixty-three percent were infected before any vaccination, 13% after the frst dose and 25% after the second. The most common symptoms were anosmia (65%), dysgeusia (56%) and cough (56%). All patients fully recovered from the infection, with no need for hospitalization. Regardless of the score used, the difference between the mean disease activity after SARS-CoV-2 infection and that at baseline did not reach statistical significance. At baseline and after infection, mean (SD) disease activity parameters were, respectively: CDAI 8.6±5.7 vs 8.6±5.7, p=0.997;SDAI 9.3±6.6 vs 9.2±6.1, p=0,928;DAS 28 4v 2.9±1.2 vs 2.9 ±1.2, p= 0.818;BASDAI 3.6 ±2.6 vs 3.2±2.7, p=0.506;ASDAS 2.2±1.2 vs 2.2±1, p=0.721. The number of patients unresponsive to bDMARDs (according EULAR, ASDAS, ASAS, ACR and PsARC) before the infection wasn't different from post-infection. Conclusion: Our study suggests that SARS-CoV2 infection has no negative impact on PsA disease activity and bDMARD responses. However, more studies are still needed to better understand the long-term effects of SARS-CoV2 infection.

COVID-19 in PATIENTS with INFLAMMATORY RHEUMATIC DISEASES-DATA from the ROMANIAN REGISTRY of RHEUMATIC DISEASES

Background: Registries are providing real-life, long-term data relevant to safety, efficacy and long-term outcomes in patients with various rheumatic diseases. The Romanian Registry of Rheumatic Diseases (RRBR) collects efficacy and safety data, for patients with infammatory rheumatic conditions treated with bio-logics and targeted synthetic DMARDs in the country. Infections are the most frequently adverse events associated with biologics exposure. Objectives: To analyze the distribution, severity class and outcome of infection with SARS-CoV-2 in infammatory arthritides during the last 2 years of COVID-19 pandemic. Methods: We collected data for the past 2 years (2020 and 2021) from the RRBR, for the three main infammatory rheumatic diseases (Rheumatoid Arthritis-RA, Spondyloarthritis-SpA and Psoriatic Arthritis-PsA): treatment exposure (drug class) at the time of COVID-19 diagnosis, severity class (mild, moderate, severe), the disease outcome (recovered, disabled, death). Finally, we compared those data to reported numbers of COVID-19 infections in the general population, aiming to observe if there is a signifcant difference between the two groups. Results: The study included 9469 patients with infammatory rheumatic disease, in 298 (3.14%) patients a history of COVID-19 infection was recorded: 160 (53.69%) were diagnosed with RA, 116 (38.92%) with SpA and 22 (7.28%) with PsA. At the moment of COVID-19 infection, 200 patients were receiving anti-TNF inhibitors (67.11%), 27 JAK inhibitors (9.06%), 24 tocilizumab (8.05%), 23 rituximab (7.71%), 9 anti-IL17A monoclonal antibodies (3.02%) and 4 abat-acept (1.34%). More than half of the cases were mild-59.39% (177), whereas moderate forms were noted in 26.17% (78) and severe in 14.09% (42) of the total infected patients. Out of the 42 severe COVID-19 cases, 11 (26.19%) were treated with rituximab, 18 (42.85%) with TNF inhibitors, 7 (16.66%) with JAK inhibitors, 4 (9.52%) with tocilizumab, 1 (2,38%) with secukinumab and 1 (2.38%) with abatacept. Almost all cases recovered: 286 (95.97%) patients, while 12 (4.02%) deaths were recorded. The patients who died were on treatment with rituximab (5), tofacitinib (3), etanercept (2), secukinumab (1) and tocilizumab (1). Data from the National Public Health Institute showed a rate of COVID-19 infection in the general population of 9.36%, out of which 96.7% had a favorable outcome, while 3.26% deaths were reported. Conclusion: This study confrms that patients receiving treatment with rituxi-mab are at risk for a worse COVID-19 outcome. The increased number of severe cases and deaths related to COVID19 in patients receiving TNF inhibitors may be explained by the large use of this therapeutic option. Surprisingly, we noted 4 severe cases and one death related to COVID19, in patients treated with tocilizumab. We observed no signifcant differences in death rates and the outcomes of COVID-19 in patients with rheumatic diseases treated with biological therapies and the general population. The low rate of SARS-CoV-2 reported infections in the registry, compared to the general population, is most probably due to the commonly found underreporting of adverse events in registries.

PROSPECTS FOR THE USE OF MONOCLONAL ANTIBODIES TO INTERLEUKIN 23 GUSЕLKUMAB IN PSORIATIC ARTHRITIS: NEW DATA

Among the pathophysiological mechanisms of immune-mediated inflammatory diseases (IMIDs), specific attention has been paid to the abnormal activation of Th17 type immune response related to the dysregulated synthesis of cytokines forming the interleukin (IL)-23 and IL-17 axis. IL-23 blockade is an innovative approach to the treatment of psoriasis and psoriatic arthritis (PsA). Much of the interest has focused on guselkumab (GUS) (TREMFYA, Janssen, Johnson & Johnson, USA), a fully human IgG λ monoclonal antibody (mAb) targeting the p19 IL-23 subunit and the first-in-class treatment approved for patients with psoriasis and PsA. In patients with psoriasis, GUS is at least as effective as other biologic therapies for PsA and is superior to ustekinumab, an anti-IL-12/IL-23 mAb, and secukinumab, an anti-IL-17 mAb. Compared with TNF-α inhibitors, GUS therapy is less likely to cause infections and does not increase the risk of the reactivation of latent TB infection. The new GRAPPA guidelines (2021) recommend GUS (and other IL-23 inhibitors) for patients with PsA resistant to conventional disease-modifying antirheumatic drugs (DMARDs), who have peripheral arthritis, enthesitis, dactylitis, psoriatic skin and nail lesions. The paper discusses new data on the efficacy of GUS in patients resistant to TNF-α inhibitors, its benefits in patients with axial PsA, and safety during the COVID-19 pandemic.

IMMUNOGENICITY AND SAFETY OF STANDARD AND THIRD DOSE SARS-COV-2 VACCINATION IN PATIENTS WITH IMMUNE-MEDIATED INFLAMMATORY DISEASES;A PROSPECTIVE COHORT STUDY

Introduction: The immunogenicity and safety following standard two-dose SARS-CoV-2 vaccination in patients with immune-mediated inflammatory diseases (IMIDs) are not well characterised, and data on third dose vaccination in this patient group are currently lacking. Methods & Aims: This prospective, observational cohort study included adult patients on immunosuppressive therapy for Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), spondyloarthritis (SpA), psoriatic arthritis (PsA), and healthy controls receiving standard two-dose SARS CoV-2 vaccination. Patients with a weak serologic response (<100 AU/ml) were allotted a third vaccine dose. Serum samples were collected prior to, and after vaccination for analyses of antibodies to the receptor-binding domain (RBD) of the SARSCoV- 2 spike protein. The aim of the study was to evaluate the immunogenicity and safety following standard and three dose SARS-CoV-2 vaccination in IMID patients on immunosuppressive therapies. Results: a total of 1641 patients (280 CD, 195 UC, 566 RA, 305 SpA, 295 PsA, median age 52 [IQR 40-63], 899 [55%] women), and 1114 healthy controls (median age 43 [IQR 32-55], 854 [77%] women), were included in the study. After standard SARS-CoV-2 two dose vaccination, 1504 (91%) patients compared to 1096 (98%) healthy controls were responders, p<0,001. Anti-RBD levels were lower in patients (median 619 AU/ml [IQR 192-4191]) than controls (median 3355 AU/ml [IQR 896–7849]), p<0,001. Response was shown in ≤90% of patients receiving methotrexate, tumor necrosis factor inhibitor (TNFi) monotherapy, ustekinumab, tozilizumab and vedolizumab, in 80–90% of patients receiving TNFi combination therapy and secukinumab and in £ 80% for JAK inhibitors (78%), and abatacept (53%) (fig.1). Lower age (OR 0.96 [95% CI 0.95–0.98]) and receiving the mRNA-1273 vaccine (OR 5.4 [95% CI 2.4–11.9]) were predictors of response. Of 153 patients with a weak response receiving a third vaccine dose, 129 (84%) became responders. After standard two dose vaccination, adverse events (AE) were reported in 50% of patients and in 78% of controls, with a comparable safety profile. Following the third dose, 44% of patients reported AEs, without new safety issues emerging. No serious AEs were reported. Conclusion: Response rate as well as anti-RBD levels were lower in IMID patients than healthy controls following standard vaccination. Third dose vaccination in serologically weak responders was safe and resulted in a response in most patients. Our data facilitate identification of patient groups at risk of an attenuated vaccine response eligible for post-vaccination serological monitoring. The data also support a third vaccine dose following standard SARS-CoV-2 vaccination to weak-responding IMID-patients. (Figure Presented) Fig.1 Anti-SARS-CoV-2 IgG antibodies following standard two dose SARS-CoV-2 vaccination according to medication group, compared to healthy controls. Violin plot showing the probability density of the data at different values, smoothed by a kernel density estimator. Each data point is a participant, and the solid orange line show the group median. The last row (CTRL vs) shows p-values for a comparison (Mann-Whitney U test) of anti-SARS-COV 2 antibodies between medication groups and healthy controls. ACE=Angiotensin converting enzyme, FL=full length, CTRL=Controls, TNF=Tumor necrosis factor inhibitor, TNF+= Tumor necrosis factor inhibitor combination therapy, MTX=methotrexate, VDZ=vedolizumab, JAK=Janus kinase inhibitor, TCZ=tocilizumab, UST=ustekinumab, ABA=abatacept, SCK=secukinumab.

IMPACT OF INTERMEDIATE TREATMENT INTERRUPTION ON SECUKINUMAB EFFICACY IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS AND ANKYLOSING SPONDYLITIS: INTERIM ANALYSIS RESULTS FROM THE SERENA STUDY

Background/Aims Secukinumab has demonstrated long-lasting efficacy and a favorable safety profile in patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). SERENA is an ongoing, longitudinal, observational study in>2900 patients with moderate to severe psoriasis, active PsA, and AS. We report interim data on impact of intermediate treatment interruption on secukinumab effectiveness in patients with active PsA or AS. Methods This analysis included data for 534 PsA and 470 AS patients enrolled in SERENA between Oct 2016 and Oct 2018 and followed-up for at least 2 years. Patients (≥18 years) with active PsA or AS were required to have received ≥16 weeks of secukinumab treatment before enrolment. Treatment interruption was defined as interruption of secukinumab therapy for at least 3 months between the last injection and re-initiation. Effectiveness assessments included swollen and tender joint count in PsA patients, and Patient Global Assessment (PtGA) and BASDAI score in AS patients before and during treatment interruption and post secukinumab re-initiation. Patients with assessments in≥2 of the time periods were included. Last assessment prior to intermediate treatment interruption was used as baseline. The assessment closest to 6 months after re-initiation was considered the post-secukinumab re-initiation assessment. Results A total of 31 (5.8%) PsA patients and 42 (8.9%) AS patients had an intermediate treatment interruption since initiation of secukinumab treatment. The mean (SD) duration of treatment interruption was 24.8 (16.4) and 26.4 (22.9) weeks for PsA and AS patients, respectively. The mean (SD) duration of secukinumab treatment before the treatment interruption was 86.8 (50.3) and 90.2 (46.9) weeks, and after the treatment interruption was 73.6 (44.4) and 63.2 (46.8) weeks. The most commonly reported reasons included adverse events (AEs;18 [58.1%] PsA, 19 [45.2%] AS), patient decision (3 [9.7%] PsA, 3 [7.1%] AS), and COVID-19 outbreak-related reasons (1 [3.2%] PsA, 6 [14.3%] AS patients). More than 80% of PsA patients and 76% of AS patients reinitiated secukinumab without a loading phase after the treatment interruption. The swollen and tender joint count increased in PsA patients from the last assessment prior to the treatment interruption (1.3 [1.0] and 7.2 [11.4];n=6) to the first assessment during the treatment interruption (4.0 [1.4] and 16.5 [19.1];n=2), and gradually decreased post secukinumab re-initiation (0.4 [0.5] and 2.0 [0.7];n=5). PtGA and BASDAI remained stable in AS patients from the last assessment prior to the treatment interruption to the first assessment during the treatment interruption and after secukinumab re-initiation. Conclusion Secukinumab intermediate treatment interruption occurred due to a variety of reasons in the real-world setting, mainly AEs and patient decision. Most patients re-initiated secukinumab treatment without a loading phase. No notable impact of the intermediate treatment interruption was observed on the effectiveness of secukinumab.