ABSTRACT
BackgroundVaccination against SARS-CoV2 had a critical role in the fight against COVID19 pandemic.A weaker humoral response to COVID19 vaccine has been found in rheumatic patients treated with Rituximab (RTX) or Mycophenolate Mofetil (MMF)[1]. Despite the evidence that anti-SARS-CoV-2 mRNA vaccines can elicit a T-cell response [2], some data show that even the cellular immunity could be impaired in rheumatic patients [3] but COVID19 serology is the only parameter that is feasible to measure in daily practice.Tixagevimab+cilgavimab are two human-derived monoclonal antibodies administered parenterally and authorized by regulatory agencies in February 2022 for pre-exposure prophylaxis (PrEP) against COVID19 from different virus variants in fragile patients.ObjectivesTo demonstrate safety and effectiveness of tixagevimab+cilgavimab.MethodsPatients with autoimmune rheumatic diseases undergoing immunosuppressive treatment with RTX or MMF during the vaccination campaign were enrolled between April and June 2022. All patients must have anti-spike antibody levels below the protective threshold (defined by anti-spike IgG titre <250 BAU/ml) after receiving at least 2 vaccine doses.Patients were monitored with a questionnaire every month about COVID19 symptoms (including respiratory and gastrointestinal symptoms, anosmia and ageusia, skin rash and potential contact with COVID19+ subjects) and were checked for anti-spike and anti-nucleocapside antibodies titres every 2 months for a total of a 6 month follow-up. MMF dose was reduced at 1 g/die at the time of vaccine administration.ResultsFifteen patients were enrolled: 9 participants had a connective tissue disease (CTD;1 dermatomyositis, 3 anti-syntethase syndrome, 4 systemic sclerosis, 1 systemic lupus erythematosus) and 6 had vasculitis (all granulomatosis with polyangiitis). 12 of them received RTX in the preceding 12 months and 3 were taking MMF.About safety, the therapy was very well tolerated and only 4 patients (26%) reported a non-severe adverse event in the 2 weeks following drug administration (2 myalgia, 1 headache, 1 fatigue), none of them requiring hospitalization nor pharmacologic treatment.Regarding effectiveness, 3/15 patients contracted SARS-Cov2 infection (20%) with mild symptoms and no need for hospitalization nor oxygen therapy. Only 1 of them received an antiviral drug (nirmatrelvir+ritonavir). All infected patients had a CTD diagnosis. No significant correlation was observed between the type of rheumatic disease and the risk of infection or response to tixagevimab+cilgavimab.ConclusionNone of our patients developed severe adverse events after tixagevimab+cilgavimab administration and, among the 3 SARS-CoV2 infected patients, none required hospitalization nor oxygen therapy.We conclude that in our experience tixagevimab+cilgavimab is a safe and useful complementary immunization strategy to vaccination for COVID19 prophylaxis.These data will be implemented in a larger study, comprehending various immunocompromised patients from several departments.References[1] Furer et al., Ann Rheum Dis, 2021[2] Mangalakumari et al., Nat Rev Immunol, 2020[3] Picchianti-Diamanti et al., Front Immunol, 2021Charateristic of the cohortIdentificativeAgeDiagnosisRTX/MMFSARS-CoV2 InfectionHospitalizationAntiviral drugs180SScMMF-//270ASSDRTX+nono370ASSDRTX+noyes452GPARTX-//551GPARTX-//649SSc+SSjRTX-//768SScMMF-//847LESRTX-//964ASSDRTX-//1068GPARTX-//1123GPARTX-//1258DMRTX+nono1361SScMMF-//1475GPARTX-//1569GPARTX-//Figure 1.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
ABSTRACT
Background: The spread of COVID-19 pandemic raised the need to perform an additional vaccine dose to overcome the diffusion of the infection and possible life-threatening disease complications. Certain population subsets seem to be at increased risk of developing such complications, such as elderly and/or immu-nocompromised patients. Objectives: To assess the persistence of immunity following SARS-CoV-2 mRNA vaccine and the magnitude of the humoral response after the booster dose in a cohort of patients affected by giant cell arteritis (GCA). Methods: Patients with GCA regularly followed at the Rheumatology Department of the University of Pavia, Italy, who received a booster dose of SARS-CoV-2 mRNA vaccine (BNT162b2 Pfizer/BioNtech or mRNA-1273 Moderna) between October 1st and December 31st, 2021 were included. Humoral response was assessed by measuring SARS-CoV-2 Trimeric S (TSAbs) and Neutralizing (NAbs) antibodies, with a cut-off of 33.8 Binding Antibody Units (BAU)/mL and 1:10 dilution, respectively. Blood samples from each patient were drawn at least 4 months after the second and three weeks after the third vaccine dose. Results: Forty-two patients who received the booster dose of SARS-CoV-2 mRNA vaccine were enrolled. Thirty (71.4%) were females, mean age 73.2±4.7 years, disease duration 58±38 months, 19 (45.2%) had large-vessel vasculitis. Thirty-two (76.2%) were on glucocorticoids (GCs) at a mean dose of 4.9±7.8 mg/day prednisone equivalent, with 7 (16.7%) receiving ≥7.5 mg/day. Eighteen (42.9%) were on methotrexate (MTX) (mean dose 14.2±3.5 mg/week) and 8 (19.0%) were treated with subcutaneous tocilizumab (TCZ) 162 mg/week. SARS-CoV-2 serology was tested prior to the third vaccine dose at an average of 5.4±0.4 months from the former vaccination scheduled: 37 (88.1%) retained TSAbs and 30 (71.4%) NAbs. The median TSAb titre was 134 BAU/mL (IQR 97-292). Four out of 5 patients (80.0%) without TSAbs and 7 out of 12 (58.3%) without NAbs were on both GCs and MTX. Moreover, those on GCs plus MTX had lower pre-third dose TSAb titres as compared to other treatment subgroups (Figure 1A). GC doses ≥7.5 mg/day prednisone equivalents seemed to blunt NAb levels along time: 28.6% patients on GCs ≥7.5 mg/day prednisone equivalents had negative NAbs before the third dose vs. 80.0% of those taking <7.5 mg/day (p=0.007) as well as lower NAb titres (Figure 1B). Data regarding antibody response after the booster dose were available for 35 patients (83.3%). Blood collection occurred at a median of 25 days (IQR 24-32) after the third vaccine dose. All patients developed TSAbs, even those who did not respond to the previous shots. The median TSAb titre rose to 2080 BAU/mL (IQR 2080-2080) (p<0.001), while the median NAb titre increased from 1:10 to 1:320 (p<0.001). One patient (2.9%) treated with prednisone 8.75 mg/day plus MTX 12.5 mg/week did not develop NAbs. NAb levels were lower in patients taking MTX as compared to those who did not (Figure 1C,D), whereas treatment with TCZ or GCs, along with the GC dose, did not affect the magnitude of the antibody response. There were no serious adverse events from the vaccine. However, 3 patients (8.6%) experienced a disease relapse 24±5 days after the booster dose. Conclusion: In our cohort, most patients who seroconverted after the second dose of vaccine retained the humoral immunity, with excellent serocon-version rates following the booster dose. However, GCs, especially at doses ≥7.5 mg/day prednisone equivalents, may contribute to the waning of NAb titres. On the other hand, immunosuppressants like MTX, especially when combined with GCs, might impair the magnitude of the humoral response to the booster dose.