Certolizumab

Certolizumab is a Fab fragment of a humanized monoclonal antibody against tumor necrosis factor-alpha (TNF-alpha). Differing from the other TNF-alpha inhibitors due to the absence of Fc fragment and pegylation, it binds to both the soluble and transmembrane forms of TNF-alpha, creating a strong TNF-alpha blockage. Previously approved for psoriatic arthritis, certolizumab received another approval from FDA in 2018 for the treatment of moderate to severe chronic plaque psoriasis that does not respond to conventional systemic treatments or for which these treatments are contraindicated. Administered via subcutaneous injections, certolizumab also has a low-dose option for patients weighing less than 90 kg. Certolizumab is considered a safe biological drug that can be preferred during pregnancy and lactation.Copyright © 2022 by Turkish Society of Dermatology and Venereology.

Experience of Baricitinib in a Real-World Population with Efficacy and Side Effects: A South London Regional Analysis

Background/Aims Baricitinib is the most common Janus Kinase inhibitor (JAKi) used in the treatment of rheumatological conditions. Whilst randomised controlled trials have demonstrated the efficacy and safety profile of baricitinib, real-world data on the experience of JAKi use in clinical practice is lacking. The aim of this analysis was to evaluate baricitinib use in a real-world patient population in South London. Methods We looked at two rheumatology departments in South London (St George's Hospital;a tertiary teaching centre and Kingston Hospital;a district general hospital). All patients prescribed baricitinib between January 2017 to June 2022 were included. A retrospective assessment of electronic patient notes was performed to evaluate disease activity (determined by DAS-28 scores at baseline, 3-6 months and presently);adverse effects including side effects, rates of and reasons for discontinuation;and prescribing practice, including previous use of other biological disease modifying anti-rheumatic drugs (bDMARDs). Baseline data including age, gender, co-morbidities and rheumatological diagnoses were also included. Results 233 patients were included in this evaluation, with seropositive rheumatoid arthritis being the most common diagnosis (58%) and with a significant female population (87%). Baricitinib improved average DAS-28 scores from 5.75 (range 3.57-8.3) at baseline to 3.23 (range 0.28-7.49) at 3-6 months post-baricitinib, with the most recent DAS-28 score of 2.90 (range 0.56-6.77). Rates of adverse effects were low as shown in Table 1. Baricitinib was discontinued in 60/233 patients, with average duration to discontinuation of 9.5 months. The most common reasons for discontinuation were: ineffective disease control (28/60), recurrent bacterial infection (5/60), deranged liver function (3/60) and venous thromboembolism (2/60). Eight patients died whilst taking baricitinib. Where documented, the causes of death were Covid-19 (4/8) and malignancy (1/8). 110 out of 233 patients had received other bDMARDs before starting baricitinib. Documented reasons for baricitinib choice over tumour necrosis factor inhibitors (TNFi) included: previous lack of response to TNFi (89/233), contra-indication to TNFi (11/233) and preference of oral route (10/ 233). Conclusion Our real-world study of JAKi use shows that baricitinib is efficacious in the treatment of rheumatological conditions. Moreover, baricitinib is well tolerated, with low rates of adverse effects and subsequent discontinuation. (Table Presented).

From Covid to Bovid to Ovid: A Case of Disseminated Cryptococcus Neoformans

Case Report: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus, with C. neoformans and C. gattii being the most common species to cause human disease. Immunocompromised individuals are predisposed to infections with C. neoformans, which has known predilection to CNS and pulmonary lymph nodes. We present a unique case of disseminated cryptococcosis in the setting of end-stage renal disease (ESRD), cirrhosis, tumor necrosis factor inhibitor use and steroid use for COVID19. Method(s): A single-patient case report was conducted after IRB approval. Case Presentation: A 55-year-old woman with uncontrolled diabetes, lupus, rheumatoid arthritis on adalimumab, hepatitis C status post boceprevir, cirrhosis, former IV drug use, and ESRD on hemodialysis via bovine arterial-venous fistula graft presented with worsening dyspnea, cough, and altered mental status. Three months prior, patient was admitted to an outside hospital for COVID19, complicated by pulmonary embolism status post anticoagulation therapy. Patient was treated with an unknown steroid regimen, which was continued by a second outside facility when symptoms failed to improve. Patient then presented to our facility 24 hours after discharge due to continued symptoms. On admission, patient was noted to have altered mentation and hypoxia with pulmonary edema on chest x-ray and was urgently hemodialyzed. Further work-up was obtained due to non-resolving symptoms, including blood and sputum cultures, cocci serology and QuantiFERON gold. CT chest revealed bilateral consolidations. Patient was started on antibiotics for presumed hospital-acquired pneumonia. During the hospital stay, preliminarily blood cultures grew yeast and patient was started on Micafungin. However, Micafungin was changed to Liposomal Amphotericin B as ovoid structures seen on gram stain could not confirm nor rule out cryptococcus. Subsequent bronchial wash and bronchoalveolar lavage cultures, as well as final blood cultures resulted Cryptococcus neoformans. Serum cryptococcus antigen returned reactive, titer 1:512. Antibiotics were discontinued and Isavuconazonium was started with Liposomal Amphotericin B. Due to recurrent headaches, lumbar puncture was obtained and revealed lymphocytic pleocytosis without cryptococcal antigenicity. Patient completed 14 days of Liposomal Amphotericin B and Isavuconazole with continuation of Isavuconazole upon discharge. Conclusion(s): Disseminated cryptococcosis in non-HIV patients is rare in the modern HIV era. Clinicians should be aware and include it in their differential of any patient with multiple risk factors for opportunistic infection. In patients with cirrhosis and ESRD, treatment is limited given altered pharmacokinetics. Studies have shown improved survival with the addition of Isavuconazole in patients with disseminated cryptococcosis with CNS involvement in the setting of chronic liver disease and ESRD.

Two years of the COVID-19 pandemic in the population of Czech patients with inflammatory bowel disease treated with biological therapy*experience of the tertiary IBD center.

Background: Inflammatory bowel disease (IBD) may be associated with a more severe course of infections and a different response to vaccination, especially in complicated IBD course and in association with immune-modifying IBD treatment. The aim of this study was to describe COVID-19 pandemic during years 2020 2022 in IBD patients with long-Term biological therapy. Method(s): A retrospective analysis of SARS-CoV-2 infection incidence in the population of 1,177 IBD (Crohn s disease or ulcerative colitis) patients with long-Term biological therapy (IBD cohort) was performed. The incidence rate, crude incidence rate and standardized incidence ratio of COVID-19 in the IBD cohort, the odds ratio of infection depending on the type of biologic therapy administered, the dynamics of COVID-19 incidence depending on the predominant SARS-CoV-2 variant in the population and the current vaccination coverage of the IBD cohort were calculated. Result(s): From January 2020 to April 2022, 548 confirmed cases of COVID-19 (46.6%) were reported in the IBD cohort, with 39% share of PCR positivity in vaccinated individuals and with 95% occurrence of infection in unvaccinated part of the IBD cohort. Standardized incidence rate ratio of COVID-19 was 27% higher in the IBD cohort compared to the general Czech population. The dynamics of the development of the number of positive cases of COVID-19 in the IBD cohort was identical to the situation in the entire country. A higher odds ratio of the chances of infection was demonstrated in patients treated with tumor necrosis factor inhibitors, but not in patients treated with anti-integrins or monoclonal antibodies against interleukins. In the IBD cohort, 85.2% of patients were properly vaccinated, which was significantly more than the vaccination rate of the entire Czech population. Discussion and conclusion: During the two pandemic years, the incidence of COVID-19 in patients with severe IBD and long-Term biological treatment was higher compared to the general Czech population, despite the favorable vaccination coverage of this high-risk patients group. A higher risk was associated with tumor necrosis factor inhibitor therapy.Copyright © 2023 Galen s.r.o.. All rights reserved.

Humoral immune response to COVID-19 vaccination in psoriasis patients on biologic therapy is impaired compared to healthy controls

Different vaccines have been developed to counteract the SARS-CoV2 pandemic. A competent immune system is a prerequisite for the development of appropriate immune protection after vaccination. Therapy with biologics for psoriasis patients, however, aims to suppress certain immune responses in the skin thus interfering with the inflammatory cascade. The purpose of this study was to investigate the measurable immune response of psoriasis patients receiving biologic therapy differs from healthy controls not receiving biologic treatment. Therefore, we collected blood samples within a fixed time frame (4 to 8 weeks) after complete two times vaccination against COVID19. We examined IgG and IgA antibody titer via ELISA analysis. The psoriatic group comprised persons under treatment with IL-17 inhibitors, IL-23 inhibitors and TNF alpha inhibitors. There was no significant difference between the psoriatic patients and control subjects concerning the time span between vaccination and blood sampling. The results showed significantly lower anti-COVID19 IgG antibody titers lower in patients under biologic treatment compared to the healthy control group without treatment. These results may help to adjust recommendations for future vaccinations in vulnerable immune suppressed patients.Copyright © 2023

Long-term safety of 3 years of ozanimod in moderately to severely active ulcerative colitis: an interim analysis of the True North open-label extension

Background: The phase 3, randomised True North (TN) study demonstrated the efficacy and safety of ozanimod for up to 52 weeks in patients (pts) with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) aims to assess the long-term efficacy and safety of ozanimod in UC. This analysis evaluated the cumulative long-term safety of ozanimod in these studies, which included pts with up to ~3 years of treatment exposure. Method(s): In TN, pts were randomised to once-daily ozanimod 0.92 mg or placebo, or to open-label ozanimod for a 10-week induction period. Ozanimod clinical responders were rerandomised at Week 10 to ozanimod or placebo in the maintenance period through Week 52. TN pts were eligible to enrol in the OLE and receive ozanimod if they did not achieve clinical response at the end of induction (Week 10), lost response during maintenance, or completed maintenance at Week 52. This interim analysis of the TN OLE (data cutoff: 10 January 2022) included all pts who entered the OLE from TN (n=823). Safety was monitored from the first dose of ozanimod in TN and throughout the subsequent OLE. Exposureadjusted incidence rates per 100 patient-years (PY) were calculated. Result(s): The average age of TN OLE study participants was 41.7 years (+/-13.6), 41% were female, 62% had left-sided UC disease, and 35% had prior exposure to tumor necrosis factor inhibitors. Total PY exposure to ozanimod was 2219 years (mean [SD] exposure = 2.7 [1.6]). The most frequent treatment-emergent adverse events (TEAEs) reported through OLE Week 94 (up to 146 weeks of continuous treatment) are listed in the Table. Most TEAEs were nonserious;TEAEs leading to discontinuation were uncommon. Bradycardia was reported in 3 pts (0.4%;EAIR 0.1/100 PY;2 in TN and 1 in OLE;no pts were discontinued from treatment). Macular edema was reported in 2 (0.2%;EAIR 0.1/100 PY) pts. Reductions in ALC were common (470 [57.1%] had ALC < 500 cells/mm3), as previously described, but ALC reductions were not associated with the occurrence of TEAEs. Malignancies were uncommon (n=13 [1.6%];EAIR 0.6/100 PY), and included 6 basal cell carcinomas and 3 colorectal neoplasms. Two deaths were reported: 1 due to COVID-19 and 1 sudden death. Investigators deemed both to be unrelated to treatment. Ozanimod was not associated with an increased risk of ischemic heart disease or thromboembolic events. Conclusion(s): Long-term exposure to ozanimod for up to 3 years was well tolerated in pts with moderately to severely active UC. No new safety signals were observed with long-term ozanimod use in UC (2219 PY exposure). Safety findings are consistent with previous reports from the UC and multiple sclerosis development programs (>16,512 PY exposure). (Table Presented).

Methodology, efficacy and safety of fecal microbiota transplantation in treating inflammatory bowel disease

Fecal microbiota transplantation (FMT), as an emerging therapy, can be used to treat microbiota related diseases. Progresses in donor screening, washed microbiota preparation, microbiota delivery routes, clinical administrative strategies, and long-term safety are moving FMT forward. Increasing clinical studies, especially those randomized controlled trials about ulcerative colitis and pilot real-word studies about serious inflammatory bowel disease (IBD), have been conducted. This review presents the latest findings about the efficacy, safety and methodology of FMT in treating IBD.Copyright © 2020 The Authors

A Comprehensive Mini-review on COVID-19 Pathogenesis on Perspectives of Cytokine Storm and Recent Developments in Anti-Covid Nucleotide Analogues

The world has been rocked by the 2019 coronavirus disease (COVID-19), which has significantly changed our way of life. Despite the unusual measures taken, COVID-19 still exists and affects people all over the world. A remarkable amount of study has been done to find ways to combat the infection's unsurpassed level. No ground-breaking antiviral agent has yet been introduced to remove COVID-19 and bring about a return to normalcy, even though numerous pharmaceuticals and therapeutic technologies have been reused and discovered. The cytokine storm phenomenon is of utmost importance since fatality is strongly connected with the severity of the disease. This severe inflammatory phenomenon marked by increased amounts of inflammatory mediators can be targeted for saving patients' life. Our analysis demonstrates that SARS-CoV-2 specifically generates a lot of interleukin-6 (IL-6) and results in lymphocyte exhaustion. Tocilizumab is an IL-6 inhibitor that is currently thought to be both generally safe and effective. Additionally, corticosteroids, tumor necrosis factor (TNF)-blockers and Janus kinase (JAK) inhibitors could be effective and dependable methods to reduce cytokine-mediated storm in SARS-CoV-2 patients.Copyright © The Author(s) 2023.

Could biological disease modifying anti rheumatic drugs (bDMARDs) and small molecules have a key role in preventing COVID-19 infection?

Background: The clinical manifestations of COVID-19 infection are very heterogeneous. Rheumatic patients should be more susceptible to develop severe forms of COVID-19 pneumonia due to an unbalanced immune response and treatment immunodepressants (disease modifying anti rheumatic drugs-DMARDs). Aims and objectives: To investigate if the chronic use of biological DMARDs and small molecules may increase the susceptibility to COVID-19 and to developing severe disease. Method(s): We studied 43 consecutive patients on bDMARDs or small molecules from March 2020 to January 2022. Data collection included: rheumatic diagnosis, comorbidities, smoking history and COVID-19 clinical course according to MEWS (modifying early warning score) in 4 stages: 0=no symptoms at all;no hospitalization;1=not complicated disease with mild or non-specific symptoms;no hospitalization;2=mild pneumonia with clinical and/or radiological diagnosis, without any signs of severity;no hospitalization;3=severe pneumonia with respiratory failure with need of hospitalization;4=hospitalization in ICU or sub-ICU. Result(s): 30 patients (69.8%) got COVID infection: 26 were not hospitalized (MEWS 0=3.3%;1=70%;2=13.3%);of the four patients that required hospitalization, none was intubated. Hospitalized patients were obese and had hypertension, and 3 had a positive smoking history. Patients taking TNF-inhibitors compared to other treatment were not at major risk of COVID-19 infection (p=0.041). Conclusion(s): Rheumatic patients taking bDMARDs or small molecules appear more susceptible to contract SARSCoV-2 infection, but the development of severe forms appears to be rare.

Studying the Predictive Effects of Bacterial Carotenoids in the Treatment of Endometriosis Using Virtual Screening Methods

Background: Endometriosis is a chronic inflammatory disease defined as the presence of endometrial tissue outside the uterus, which causes pelvic pain and infertility. Cytokines appear to play vital roles in the development and progression of endometriosis and associated infertility. Tumor necrosis factoralpha (TNF-alpha) is a multifunctional pro-inflammatory cytokine, responsible for autoimmune and inflammatory disorders. TNF- alpha plays an important role in endometrial physiology as well as during early implantation. In addition, this cytokine has a considerable pathophysiological function in diseases such as menorrhagia, endometriosis, or infertility due to its regulatory impact on proliferation, differentiation, and angiogenesis in the human endometrium. In women with endometriosis, TNF-alpha levels increases in peritoneal fluid and serum significantly. In the present study, we focused on finding novel small molecules that can directly block TNFalpha- hTNFR1 (human TNF receptor 1) interaction. Method(s): In this regard, TNF-alpha inhibiting capacity of natural carotenoids was investigated in terms of blocking TNF-alpha-hTNFR1 interaction with the help of a combination of in silico approaches, based on virtual screening, molecular docking, and molecular dynamics (MD) simulation. Result(s): A total of 125 carotenoids were selected out of 1204 natural molecules, based on their pharmacokinetics properties, and they all met Lipinski's rule of five. Among them, sorgomol, strigol, and orobanchol had the most favorable DELTAG with the best pharmacokinetics properties and were selected for MD simulation studies, which explored the complex stability and the impact of ligands on protein conformation. It was shown that sorgomol formed the most hydrogen bonds, resulting in the highest binding energy with the lowest RMSD and RMSF. Conclusion(s): Our results showed that sorgomol was the most appropriate candidate as a TNF-alpha inhibitor. In conclusion, the present study could serve to expand possibilities to develop new therapeutic small molecules against TNF-alpha which plays an important role in the inflammation of endometriosis.

Treatment outcome of tofacitinib dose reduction to 5 mg BID vs remaining on 10 mg BID in patients with Ulcerative Colitis who were in stable remission on 10 mg BID: Updated 30-month data from the double-blind, randomised RIVETING study

Background: Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. The long-term, Phase 3b/4 RIVETING study (NCT03281304) assessed the efficacy and safety of tofacitinib dose reduction from tofacitinib 10 mg twice daily (BID) maintenance therapy to 5 mg BID in patients (pts) in stable remission. 1 We present a final analysis of the RIVETING study after >=30 months of treatment. Method(s): RIVETING was a double-blind, randomised, parallelgroup study with a 42-month (M) duration. Eligible pts had received tofacitinib 10 mg BID for >=2 consecutive years in an open-label, long-term extension study (NCT01470612), had been in stable remission for >=6 months and corticosteroid-free for >=4 weeks prior to baseline. The primary efficacy endpoint was remission at M6 based on modified Mayo (mMayo) score (endoscopic and stool frequency subscores of <=1 and rectal bleeding subscore of 0).1 RIVETING was terminated (primary objective met) when all pts had passed M30 (or discontinued);some pts had already completed all visits up to M42. Here, we assess efficacy at M30 and safety throughout. Result(s): Overall, 140 pts were randomised (1:1) to tofacitinib 5 or 10 mg BID;50.0% and 62.9% were in remission based on mMayo score at M30 in the 5 and 10 mg BID dose groups, respectively, with consistent findings observed for other secondary efficacy endpoints (Table 1). At M30, observed differences for mMayo remission between tofacitinib 10 and 5 mg BID were generally greater in the subgroup with a baseline endoscopic subscore of 1 vs 0 and in the subgroup with vs without prior tumour necrosis factor inhibitor (TNFi) failure (Table 1). The percentage of pts who experienced loss of remission by M30, as estimated from Kaplan-Meier curves, was numerically higher in the 5 vs the 10 mg BID dose group (28.1%;95% confidence interval [CI], 17.68-39.49 vs 21.7%;95% CI, 12.21-32.95, respectively). Table 2 shows adverse events of special interest, by dose group. One death occurred due to fatal coronavirus disease 2019 pneumonia (10 mg BID). Conclusion(s): These long-term data showed that most pts in stable remission on tofacitinib 10 mg BID maintenance therapy maintained mMayo score remission through M30 after dose reduction to 5 mg BID. Dose group difference in remission at M30 was consistent with that at M6.1 Differences in remission between the tofacitinib 5 and 10 mg BID groups were greater in subgroups with an endoscopic subscore of 1 vs 0 and in subgroups with vs without prior TNFi failure. Overall, safety findings were consistent with tofacitinib's known safety profile;incidence of serious infections and herpes zoster was numerically higher in the tofacitinib 10 vs 5 mg BID group. (Table Presented).

Long COVID-19 in autoimmune and rheumatic diseases: data from COVID-19 vaccination in autoimmune diseases study

Background/Aim: Long COVID-19 is one of the post-infection challenging issues. We aimed to assess the prevalence and characteristics of this syndrome in patients with autoimmune and rheumatic diseases (AIRDs) through a multicentre international e-surveys (The COVID-19 Vaccination in Autoimmune Diseases) COVAD study. Method(s): The COVAD group comprised of collaborators from 109 countries. An online survey platform was conducted in Jan-July 2022 to capture self-reported COVID-19 infection and vaccination data in patients with AIRDs and healthy controls (HCs). Long COVID-19 was defined as per WHO definitions as persistence of symptoms beyond 3 months of COVID-19 infection. Descriptive statistics and multivariable regression adjusted for age, gender, ethnicity, and disease modifying anti-rheumatic drugs (DMARDs) were employed. Result(s): Among the 7666 complete survey respondents, 1677 who had taken the survey >90 days of last COVID-19 infection were analyzed. Among them, a total of 8.1% (n = 136) had long COVID-19 syndrome and the median age was 46 (34-55) years, with Male: Female ratio of 1:6.3. The prevalence of long COVID-19 was significantly higher in patients with AIRDs compared to HCs (OR 2 [1.3-2.9], P < 0.001). Respondents with long COVID-19 had worse PROMIS 10a quality of life global physical and mental health score, as well as fatigue and pain VAS compared to those without post-COVID- 19 (all P < 0.001). Among patients with AIRDs, those with long COVID-19 reported to have higher flares of AIRDs following COVID-19 infection (OR 4.3, P < 0.01). On multivariable regression analysis, the characteristics of patients with long COVID-19 were female gender, Caucasian ethnicity and presence of comorbid insomnia. Presence of fatigue, muscle aches, dyspnoea and loss of taste during previous COVID-19 infection were the significant predictors of long COVID-19. Among patients with AIRDs, comorbidities (OR 2.0;95% CI: 1.08-3.6, P = 0.026), and advanced treatment (OR: 1.9;95% CI: 1.08-3.3, P = 0.024), or intensive care (OR: 3.8;95% CI: 1.01-14.4, P = 0.047) for severe COVID-19 were risk factors for long COVID-19. The use of rituximab, iv immunoglobulins (IVIG), mycophenolate mofetil and anti-TNF agents use also predicted long COVID-19. Conclusion(s): Patients with AIRDs are at higher risk of long-COVID- 19 syndrome. Associated comorbid conditions and advanced treatment or intensive care for severe COVID-19 confer a higher risk.

Incidence of COVID-19 hospitalization in patients with psoriasis taking systemic immunomodulators

Background: Current research on COVID-19-related outcomes in patients with psoriasis, particularly regarding influence of treatments, are subject to lack of comparator group, selection bias, and insufficient statistical power.1 Accordingly, it remains uncertain whether immunomodulatory treatments for psoriasis enhance or decrease the risk of severe COVID-19-related outcomes, including hospitalization. Objective(s): To compare the risk of COVID-19-related hospitalization according to immunomodulator treatment type in patients with psoriasis Methods: Retrospective cohort study of the Explorys database in the United States between March 1st, 2020 and December 31st, 2020. Psoriasis diagnosis was defined by at least 2 ICD-9 or ICD-10 diagnosis codes prior to March 1st, 2020. Drug exposure was classified as biologic or traditional immunosuppressive (methotrexate, cyclosporine, apremilast) treatment based on prescription order in the 3 months preceding March 1st, 2020. Biologic treatments included TNFalpha, IL-12/IL-23, IL-17A, IL-23 and JAK inhibitors. The primary outcome was defined as hospital admission with diagnosis of COVID-19 or positive lab test occurring between admission and discharge date. Propensity score weighting was used to compare COVID-19-related hospitalization between treatment groups, adjusting for comorbidities and demographic characteristics. Result(s): A total of 51,606 psoriasis patients aged 18-88 were included. Crude cumulative incidence of COVID-19 hospitalization per 1,000 psoriasis patients was 3.4 in the biologic group (9/2,669), 9.5 in the traditional immunosuppressive group (15/1,585), and 3.9 in those receiving neither drug class (184/47,352). Incidence was 4.7 (6/1,282) and 14 (13/898) per 1,000 patients among those receiving TNF-alpha inhibitors and methotrexate, respectively. After propensity-score weighting, risk of COVID-19-related hospitalization for patients receiving any biologic was lower than that of patients receiving traditional immunosuppressives (RR 0.39, 95% CI 0.16, 0.92), and those receiving neither drug class (RR 0.66, 95% CI 0.32, 1.34). TNF-alpha inhibitor use was associated with lower risk of hospitalization relative to methotrexate use (adjusted RR 0.39, 95% CI 0.14, 1.06). Adjusted relative risk of hospitalization for methotrexate users relative to those receiving neither drug class was 2.78 (95% CI 1.47, 5.26). Conclusion(s): During the first wave of the pandemic in 2020, psoriasis patients using biologics were at lower risk of COVID-19-related hospitalization compared to those using traditional immunosuppressives, particularly methotrexate. Methotrexate use was associated with a substantial increase in risk of hospitalization relative to those who did not receive systemic treatments.

Adalimumab Biosimilar Efficacy and Safety in a 5-Year-Old Patient with Severe Plaque Psoriasis During SARS-CoV-2 Pandemic Outbreak

BACKGROUND: Psoriasis is a chronic inflammatory disease that affects 2% of population. About 0.5–2% of psoriatic cases develop during pediatric age. In most cases, the condition is responsive to topical treatment. However, a small percentage of children require systemic treatment with conventional systemic drugs or biological agents, such as anti-tumor necrosis factor (TNF)-α. Adalimumab (ADA) is an anti-TNF-α recently approved for pediatric psoriasis in the European Union (from 4 years of age, 2015). CASE PRESENTATION: We describe our experience treating a 5-year-old female patient affected by severe plaque psoriasis with ADA biosimilar during SARS-CoV-2 pandemic outbreak also using teledermatology. CONCLUSION: The case reported in this article highlights the safety and the effectiveness of ADA biosimilar MSB11022 (Idacio®) in the treatment of a 5-year-old female affected by plaque psoriasis and paves the way to bigger trials for a more extensive use of TNF-α inhibitor biosimilars for psoriasis in pediatric population.

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.

Abstracts of the Joint Annual Meeting of the Swiss Society of Rheumatology and the Swiss Society of Physical Medicine and Rehabilitation

The proceedings contain 47 papers. The topics discussed include: increased humoral immune response after vaccination with mRNA-1273 vs BNT162b2 in patients with inflammatory rheumatic diseases;comparison of anti-fracture effectiveness of denosumab versus bisphosphonates in a registry-based, real-world cohort study;comparison of drug retention of TNF inhibitors, other biologics and JAK inhibitors in patients with rheumatoid arthritis who discontinued JAK inhibitor therapy;BRD3 regulates the inflammatory and stress response in rheumatoid arthritis synovial fibroblasts;effect of methotrexate and folic acid co-administration in arthritis;early anti-S antibody levels predict anti-SARS-CoV-2 neutralizing activity over 24 weeks in RA patients after SARS-CoV-2 mRNA vaccination;effect of zoledronate on bone mineral density and bone turnover markers after long-term denosumab therapy: observations in a real-world setting;and developing a screening tool for the detection of interstitial lung disease in systemic sclerosis: the ILD-RISC score.

THE COURSE of COVID-19 INFECTION in PATIENTS with RHEUMATOID ARTHRITIS RECEIVING VARIOUS BIOLOGICAL DISEASE-MODIFYING ANTIRHEUMATIC DRUGS

Background: With the ongoing COVID-19 pandemic, the safety of biologic disease-modifying antirheumatic drugs in patients with rheumatic disease remains an important issue. Objectives: to assess the course of COVID-19 infection in patients with rheumatoid arthritis receiving various biological disease-modifying antirheumatic drugs. Methods: An analysis was made of the course of COVID-19 in patients with rheumatic diseases who were under observation at the North-Western State Medical University. I.I. Mechnikov in the period from March 2020 to November 2021. During this period, 198 (14.04%) cases of COVID-19 were registered out of 1389 patients included in the registries of the anticytokine therapy center. Among patients with rheumatoid arthritis who recovered from COVID-19 infection, 105 cases were registered, of which 53 patients received outpatient treatment, and 52 patients received inpatient treatment. In 76% of cases, patients received biological DMARDs in combination with synthetic DMARDs. Results: Exacerbation of the articular syndrome was observed only in 12 (11.4%) patients with RA during COVID-19. The low percentage of exacerbations in patients with RD on the background of COVID-19 was probably associated with the use of dexamethasone at a dose of 16-32 mg, which has the ability to reduce the activity of the immune-infammatory process in rheumatic diseases. This statement is confrmed by the fact that out of 52 patients with RA who were hospitalized for COVID-19, 16 patients (30.8%) received dexamethasone intramuscularly or intravenously, and 8 patients (15.4%) continued oral administration of this drug. Conclusion: The use of rituximab was associated with a more severe course of COVID-19, which required hospitalization in 66% of cases, compared with the group of patients treated with TNF-α inhibitors, in which hospital treatment was carried out only in 20% of cases. The introduction of blockers of co-stimulation of T-cells, IL-6 inhibitors, targeted synthetic drugs did not affect the severity of COVID-19.

SARS-COV-2 VACCINE in SPONDYLARTHRITIS PATIENTS: OVERALL MODERATE/HIGH IMMUNOGENICITY IMPAIRED by IMMUNOSUPPRESSANTS and BIOLOGICAL THERAPY

Background: We recently reported an attenuate immunogenicity in patients with autoimmune rheumatic diseases. However, the effect of spondyloarthritis (SpA) and its treatment on COVID-19 vaccine immunogenicity remains to be determined for this group of patients. We therefore aimed to evaluate humoral immune responses to inactivated SARS-CoV-2 vaccine (CoronaVac) in patients with SpA (axial spondyloarthritis and psoriatic arthritis) taking DMARDs and commonly used targeted biological therapies, compared with a control group(CG). Objectives: Evaluate immunogenicity and safety of CORONAVAC (Sninovac, Beijing) in Spondyloarthritis (SpA) patients. Methods: Prospective observational cohort patients diagnosed with 194 SpA and 183 CG were vaccinated with CoronaVac in two doses with a 28-days interval. 194 patients completed the study and could be paired with CG for immunogenicity analysis. Blood samples were collected in the days 0, 28 and 69 (D69) to evaluate anti-SARS-CoV-2 IgG seroconversion(SC) and presence of neutralizing antibodies (NAb) in participants with negative IgG and NAb at baseline. Results: Patients and GC were comparable regarding age (p=0.93) and sex (p=1.00). Immunogenicity at D69 showed a moderate/high SC (80.2% vs. 95.7%, p<0.0001) and Nab positivity (61.6% vs. 82.7%, p<0.0001) in SpA but lower than CG. Factors associated with lower immunogenicity were older age (56.8 vs. 51.4;p=0.03318) and higher frequencies of prednisone (25.7% vs 4.2%;p=0.0004), methotrexate (51.4% vs 40.1%, p=0.0016) and TNF inhibitor (TNFi) (62.9% vs 34.5%, p=0.0035). Likewise, prednisone (17.6% vs. 2.8%, p=0.0013) and TNFi (50% vs 33.9%;p=0.0408) were associated with diminished NAb positivity. Sulfasalazine was associated with higher SC rates (8.6% vs. 26.8%, p=0.0246) and NAb positivity (13.2% vs. 29.4%, p=0.0168). The multivariate analysis revealed that older age (p=0.037), prednisone (p=0.001), TNFi (p=0.016), and methotrex-ate(p=0.017) were independently associated with lower SC while prednisone (p=0.006) and TNFi (p=0.027) were also associated with reduced NAb response. Conclusion: Our fnding of an excellent safety and moderate/high SC rate in SpA supports the recommendation of CoronaVac vaccination. The impaired immune response in the minority of patients under immunosuppressive and biological therapy requires novel strategies to enhance antibody response in this subgroup of patients.