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1.
J Int Med Res ; 50(4): 3000605221090363, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1779533

ABSTRACT

OBJECTIVE: Hydroxychloroquine (HCQ) has been used during the coronavirus disease 2019 (COVID-19) pandemic because of its reported anti-viral activity. This study examined the association of chronic HCQ use with the incidence and complications of COVID-19. METHODS: This retrospective cohort study included adults with rheumatoid arthritis and/or systemic lupus erythematosus who visited rheumatology clinics in three tertiary hospitals in Riyadh, Saudi Arabia between January 2019 and December 2020. Patients were categorized into two groups based on HCQ use. Data were obtained from the electronic health record and by interviews with patients. The primary study objective was the incidence of COVID-19 and its complications from March 2020 to February 2021. RESULTS: Almost 11% of the study cohort was positive for COVID-19, and the incidence of COVID-19 was similar between HCQ users (11.11%) and nonusers (10.86%). Disease complication rates were similar in the study arms, and they mainly included fever, dry cough, fatigue, and breathing difficulty. CONCLUSIONS: This study revealed no significant association between chronic HCQ use and the incidence of COVID-19, and disease complications were similar in the study arms.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , COVID-19 , Lupus Erythematosus, Systemic , Adult , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , COVID-19/drug therapy , COVID-19/epidemiology , Humans , Hydroxychloroquine/adverse effects , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Retrospective Studies
2.
RMD Open ; 8(1)2022 Mar.
Article in English | MEDLINE | ID: covidwho-1774982

ABSTRACT

OBJECTIVES: To assess antibody and T cell responses to SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs). METHODS: This prospective study recruited 100 patients with RA on a variety of DMARDs for antibody and T cell analysis, pre-vaccination and 4 weeks post-vaccination. Positive antibody response was defined as sera IgG binding to ≥1 antigen. Those that remained seronegative after first vaccination were retested 4 weeks after second vaccination; and if still seronegative after vaccination three. A T cell response was defined an ELISpot count of ≥7 interferon (IFN)γ-positive cells when exposed to spike antigens. Type I IFN activity was determined using the luminex multiplex assay IFN score. RESULTS: After vaccine one, in patients without prior SARS-CoV-2 exposure, 37/83 (45%) developed vaccine-specific antibody responses, 44/83 (53%) vaccine-specific T cell responses and 64/83 (77%) developed either antibody or T cell responses. Reduced seroconversion was seen with abatacept, rituximab (RTX) and those on concomitant methotrexate (MTX) compared to 100% for healthy controls (p<0.001). Better seroconversion occurred with anti-tumour necrosis factor (TNF) versus RTX (p=0.012) and with age ≤50 (p=0.012). Pre-vaccine SARS-CoV-2 exposure was associated with higher quantitative seroconversion (≥3 antibodies) (p<0.001). In the subgroup of non-seroconverters, a second vaccination produced seroconversion in 54% (19/35), and after a third in 20% (2/10). IFN score analysis showed no change post-vaccine. CONCLUSION: Patients with RA on DMARDs have reduced vaccine responses, particularly on certain DMARDs, with improvement on subsequent vaccinations but with approximately 10% still seronegative after three doses.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , COVID-19 , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Prospective Studies , SARS-CoV-2 , T-Lymphocytes , Vaccination
4.
Ren Fail ; 44(1): 415-425, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1730388

ABSTRACT

OBJECTIVES: Hydroxychloroquine/chloroquine has been widely used as part of the standard treatment for patients with coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to determine whether hydroxychloroquine/chloroquine increases the risk of acute kidney injury (AKI) in COVID-19 patients. METHODS: PubMed and Embase were searched for related publications from inception to Dec 31, 2021, including randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing the risk of AKI and/or increased creatinine in COVID-19 patients receiving hydroxychloroquine/chloroquine and other controls (active treatment and placebo). We conducted separate meta-analyses for RCTs and NRSIs based on fixed-effect model, with odds ratios (ORs) being considered as effect sizes. RESULTS: We included 21 studies in the analysis, with 12 were RCTs. Based on the RCTs, compared to placebo, the OR was 1.19 (95% confidence interval [CI]: 0.86, 1.64; p = .30, n = 4, moderate quality) for AKI and 1.00 (95%CI: 0.64, 1.56; p = .99, n = 5, moderate quality) for increased creatinine for patients received hydroxychloroquine/chloroquine treatment; compared to active treatment, the odds was 1.28 (95%CI: 0.65, 2.53; p = .47, n = 2, low quality) for AKI and 0.64 (95%CI: 0.13, 3.20; p = .59, n = 1, low quality) for increased creatine. Evidence from NRSIs showed slightly increased odds of AKI, with low quality. CONCLUSION: Based on current available studies which were graded as low to moderate quality, there is insufficient evidence to conclude that hydroxychloroquine/chloroquine use is associated with increased risk of AKI or raised creatinine. Abbreviations: AKI: acute kidney injury; COVID-19: Coronavirus Disease 2019; RCT: randomized controlled trials; NRSI: non-randomized studies of interventions; OR: odds ratios; ROBIS-I: Risk Of Bias In Non-randomized Studies - of Interventions.


Subject(s)
Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Antirheumatic Agents/adverse effects , COVID-19/drug therapy , Hydroxychloroquine/adverse effects , Humans
5.
Turk J Med Sci ; 51(SI-1): 3391-3404, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1726158

ABSTRACT

In the Wuhan province of China, almost two years ago, in December 2019, the novel Coronavirus 2019 has caused a severe involvement of the lower respiratory tract leading to an acute life-threatening respiratory syndrome, coronavirus disease-19 (COVID-19). Subsequently, coronavirus 2 (SARS-CoV-2) rapidly spread to the entire world causing a pandemic and affected every single person on earth either directly or indirectly with destroying all facets of social life and economy. Since the announcement of COVID-19 as a global pandemic, we have witnessed tremendous scientific work on all aspects of COVID-19 across the globe, which has never been witnessed before. The most remarkable achievement would be the introduction of vaccines, which provide protection from the severe infection and is the only premise for the control of disease. However, despite the tremendous work, the number of treatments either antiviral or immunomodulatory for infected patients are considerably limited, yet disease is causing substantial morbidity and mortality. COVID-19 follows heterogenous disease course among infected individuals, and dysregulated immune system is primarily responsible for the worse outcomes. Immune deficiency, being on corticosteroids for inflammatory diseases, delayed interferon response and advanced age adversely influence prognosis with impairing viral clearance. On the other hand, exuberant immune response with features of cytokine storm is the leading cause of death, which can be alleviated by use of either general immunosuppression with corticosteroids or selective neutralization of potent pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6. Herein, we summarized the potential effective immunomodulatory treatments emphasizing in which patient population it is the most suitable, which dose should be administered, and which is the most appropriate timepoint to administer the drug during the course of the disease.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antirheumatic Agents/therapeutic use , COVID-19/drug therapy , COVID-19/immunology , Antiviral Agents/therapeutic use , Cytokine Release Syndrome , Cytokines/immunology , Humans , Pandemics , SARS-CoV-2
6.
J Clin Rheumatol ; 28(2): e348-e352, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1703196

ABSTRACT

OBJECTIVES: The aim of this study was to examine the incidence of coronavirus disease 2019 (COVID-19) among patients with immunomediated inflammatory diseases (IMIDs) treated with biologic or targeted synthetic disease-modifying antirheumatic drugs (bDMARDs and tsDMARDs) and to evaluate the influence of either IMIDs or related therapies on the incidence and evolution of COVID-19. METHODS: This observational, cross-sectional study was conducted from January 31, 2020, to May 15, 2020. Data of 902 patients were obtained from clinical records in hospitals, primary care units, and community pharmacies. Inclusion criteria were adults with IMIDs treated with bDMARDs or tsDMARDs who started therapy 3 months prior to study commencement. Patients with poor adherence to treatments were excluded. COVID-19 was classified as "definitive" (severe acute respiratory syndrome coronavirus 2 polymerase chain reaction [PCR]-positive), "possible" (characteristic symptoms and negative PCR), and "suspected" (characteristic symptoms but PCR not performed). RESULTS: COVID-19 was diagnosed in 70 patients (11 definitive, 19 possible, and 40 suspected). The cumulative incidence of definitive COVID-19 was 1.2%. When considering all cases, the incidence was 7.8%. Patients on biosimilars tumor necrosis factor blockers were more likely to have a diagnosis of COVID-19 (odds ratio, 2.308; p < 0.001). Patients on anti-B-cell therapies had a lower incidence of infections (p = 0.046). Low rates of hospitalization (14.3%), pneumonia (14.3%), death (2.9%), or thrombosis (2.9%) were observed, and 94.3% of patients recovered. CONCLUSIONS: The cumulative incidence of confirmed cases of COVID-19 was similar to the general population, with generally low hospitalization, intensive care management, and mortality rates. COVID-19 incidence was less frequent in patients with more severe immunosuppression.


Subject(s)
Antirheumatic Agents , Biosimilar Pharmaceuticals , COVID-19 , Antirheumatic Agents/therapeutic use , Cross-Sectional Studies , Humans , Incidence , SARS-CoV-2
7.
Ann Rheum Dis ; 81(3): 351-358, 2022 03.
Article in English | MEDLINE | ID: covidwho-1685504

ABSTRACT

OBJECTIVES: Risankizumab is an interleukin-23 inhibitor under study for the treatment of patients with psoriatic arthritis (PsA). The phase 3 KEEPsAKE 2 trial investigated the efficacy and safety of risankizumab versus placebo in patients with active PsA who had previous inadequate response or intolerance to ≤2 biological therapies (Bio-IR) and/or ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD-IR). Results through week 24 are reported here. METHODS: Adults with PsA who were Bio-IR and/or csDMARD-IR were randomised to receive subcutaneously administered risankizumab 150 mg or placebo at weeks 0, 4 and 16 during a 24-week, double-blind treatment period. The primary endpoint was the proportion of patients who achieved ≥20% improvement in American College of Rheumatology score (ACR20) at week 24. Secondary endpoints assessed key domains of PsA and patient-reported outcomes. RESULTS: A total of 444 patients (median age 53 years, range 23-84 years) were randomised to risankizumab (n=224) or placebo (n=220); 206 patients (46.5%) were Bio-IR. At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (51.3% vs 26.5%, p<0.001) and all secondary endpoints (p<0.05) compared with placebo. Serious adverse events were reported for 4.0% and 5.5% of risankizumab-treated and placebo-treated patients, respectively; serious infections were reported for 0.9% and 2.3%, respectively. CONCLUSION: Treatment with risankizumab resulted in significant improvements versus placebo in key disease outcomes and was well tolerated in patients with PsA who were Bio-IR and/or csDMARD-IR. TRIAL REGISTRATION NUMBER: NCT03671148.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/drug therapy , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Male , Middle Aged , Patient Reported Outcome Measures , Treatment Outcome , Young Adult
8.
Front Immunol ; 12: 734279, 2021.
Article in English | MEDLINE | ID: covidwho-1686469

ABSTRACT

Newly emerging variants of coronavirus 2 (SARS-CoV-2) raise concerns about the spread of the disease, and with the rising case numbers, the Coronavirus disease 2019 (COVID-19) remains a challenging medical emergency towards the end of the year 2021. Swiftly developed novel vaccines aid in the prevention of the spread, and it seems that a specific cure will not be at hand soon. The prognosis of COVID-19 in patients with autoimmune/autoinflammatory rheumatic diseases (AIIRD) is more severe when compared to the otherwise healthy population, and vaccination is essential. Evidence for both the efficacy and safety of COVID-19 vaccination in AIIRD under immunosuppression is accumulating, but the effect of Interleukin-1 on vaccination in general and in AIIRD patients is rarely addressed in the current literature. In light of the current literature, it seems that the level of agreement on the timing of COVID-19 vaccination is moderate in patients using IL-1 blockers, and expert opinions may vary. Generally, it may be recommended that patients under IL-1 blockade can be vaccinated without interrupting the anti-cytokine therapy, especially in patients with ongoing high disease activity to avoid disease relapses. However, in selected cases, after balancing for disease activity and risk of relapses, vaccination may be given seven days after the drug levels have returned to baseline, especially for IL-1 blocking agents with long half-lives such as canakinumab and rilonacept. This may help to ensure an ideal vaccine response in the face of the possibility that AIIRD patients may develop a more pronounced and severe COVID-19 disease course.


Subject(s)
Antirheumatic Agents/adverse effects , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Interleukin-1beta/antagonists & inhibitors , Rheumatic Diseases/drug therapy , SARS-CoV-2/immunology , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Autoimmune Diseases/drug therapy , Autoimmune Diseases/immunology , Humans , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use , Rheumatic Diseases/immunology , Vaccination
9.
Ann Rheum Dis ; 81(5): 710-719, 2022 May.
Article in English | MEDLINE | ID: covidwho-1685510

ABSTRACT

OBJECTIVES: To evaluate the distinct impact of disease modifying antirheumatic drugs (DMARD) combination and monotherapy in immune response to an inactivated SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA). METHODS: This phase 4 prospective study analysed seroconversion (SC) of anti-SARS-CoV-2 immunoglobulin G (IgG) and neutralising antibodies (NAb) induced by the inactivated vaccine (CoronaVac) in patients with RA in comparison to controls (CG). Disease activity and treatment were also assessed. Only participants with baseline negative IgG/NAb were included. RESULTS: Patients with RA (N=260) and CG (N=104) had comparable median ages (59 years (50-65 years) vs 58 years (49.8-64 years), p=0.483). Patients with RA had moderate but lower SC (61.8% vs 94.2%, p<0.001) and NAb positivity (45% vs 78.6%, p<0.001) in comparison to CG after full vaccination. Baseline disease activity did not influence immunogenicity (p>0.05). After multivariate analyses, factors independently related to reduced SC were: older age (OR=0.79 (0.70-0.89) for each 5-year interval, p<0.001), methotrexate (OR=0.54 (0.29-0.98), p=0.044), abatacept (OR=0.37 (0.19-0.73), p=0.004) and number of DMARD (OR=0.55 (0.33-0.90), p=0.018). Regarding NAb, age (OR=0.87 (0.78-0.96) for each 5-year interval, p=0.007) and prednisone >7.5 mg/day (OR=0.38 (0.19-0.74), p=0.004) were negatively related to the presence of NAb. Further comparison of SC/NAb positivity among RA treatment subgroups and CG revealed that methotrexate/tofacitinib/abatacept/tocilizumab use, in monotherapy or in combination, resulted in lower responses (p<0.05), while tumour necrosis factor inhibitor and other conventional synthetic DMARD interfered solely when combined with other therapies. CONCLUSIONS: Patients with RA under DMARD have a moderate immunogenicity to CoronaVac. We identified that nearly all DMARD combinations have a deleterious effect in immunogenicity, whereas a more restricted number of drugs (methotrexate/tofacitinib/abatacept/tocilizumab) also hampered this response as monotherapy. These findings reinforce the need of a broader approach, not limited to specific drugs, to improve vaccine response for this population. TRIAL REGISTRATION DETAILS: NCT04754698.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , COVID-19 , Abatacept/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , COVID-19/prevention & control , COVID-19 Vaccines , Drug Therapy, Combination , Humans , Immunoglobulin G/therapeutic use , Methotrexate/therapeutic use , Middle Aged , Prospective Studies , SARS-CoV-2 , Treatment Outcome , Vaccines, Inactivated
10.
Intern Med ; 61(3): 433-438, 2022 Feb 01.
Article in English | MEDLINE | ID: covidwho-1666884

ABSTRACT

Recently, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread worldwide. Although nearly all patients incur mild-to-moderate disease from this viral infection, some develop severe manifestations with a poor prognosis. COVID-19 can also induce autoimmune disease; several cases of arthritis following COVID-19 have been documented in the literature, such as reactive arthritis and chronic arthritis. We herein report a case of psoriatic arthritis triggered by COVID-19. Although the arthritis had been refractory to glucocorticoids and methotrexate, certolizumab pegol subsequently led to remission.


Subject(s)
Antirheumatic Agents , Arthritis, Psoriatic , COVID-19 , Certolizumab Pegol , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/drug therapy , Arthritis, Psoriatic/virology , COVID-19/complications , Certolizumab Pegol/therapeutic use , Humans , Polyethylene Glycols/therapeutic use , Treatment Outcome
11.
J Acquir Immune Defic Syndr ; 87(5): 1167-1172, 2021 08 15.
Article in English | MEDLINE | ID: covidwho-1662157

ABSTRACT

BACKGROUND: Data on clinical characteristics and outcomes of people living with HIV (PLWH) hospitalized with coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) are limited. SETTING: Large tertiary health care system in the Bronx, NY. METHODS: We performed a retrospective cohort study of 83 PLWH and 4151 patients without HIV hospitalized with COVID-19 from March 10, 2020, to May 11, 2020. We compared the clinical characteristics and outcomes associated with AKI by HIV serostatus and evaluated HIV-related factors for AKI among PLWH. AKI was defined and staged using Kidney Disease Improving Global Outcomes criteria. RESULTS: The incidence of AKI in hospitalized patients with COVID-19 did not differ significantly by HIV serostatus (54.2% in PLWH vs 49.5% in patients without HIV, P = 0.6). Despite a higher incidence of stage 3 AKI (28.9% vs 17.1% P = 0.05) in PLWH compared with those without HIV, there was no significant difference in the need for renal replacement therapy (22.2% vs 13.4% P = 0.12), renal recovery (76.9% vs 82.5% P = 0.61), or dependence on renal replacement therapy (7.7% vs 3.8% P = 0.27). CD4 T-cell count, HIV-1 RNA viral suppression, and antiretroviral therapy use were not associated with AKI. AKI was associated with increased need for invasive ventilation and in-hospital death, but HIV was not an independent risk factor of in-hospital death after AKI [adjusted hazard ratio 1.01 (95% CI: 0.59 to 1.72), P = 0.98]. CONCLUSIONS: HIV-related factors were not associated with increased risk of AKI in PLWH hospitalized with COVID-19. PLWH hospitalized with COVID-19 had more stage 3 AKI, but outcomes after AKI were similar to those without HIV.


Subject(s)
Acute Kidney Injury/drug therapy , COVID-19/complications , HIV Infections/drug therapy , Acute Kidney Injury/complications , Acute Kidney Injury/epidemiology , Aged , Antirheumatic Agents/therapeutic use , COVID-19/epidemiology , Female , HIV Infections/complications , HIV Infections/epidemiology , Hospital Mortality , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , SARS-CoV-2
12.
Ann Rheum Dis ; 81(2): 225-231, 2022 02.
Article in English | MEDLINE | ID: covidwho-1622014

ABSTRACT

OBJECTIVE: To evaluate risankizumab, a biological therapy that inhibits interleukin 23, in patients with active psoriatic arthritis (PsA) who have responded inadequately or are intolerant to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). METHODS: In the randomised, placebo-controlled, double-blind KEEPsAKE 1 trial, 964 patients with active PsA were randomised (1:1) to receive risankizumab 150 mg or placebo at weeks 0, 4 and 16. The primary endpoint was the proportion of patients achieving ≥20% improvement in American College of Rheumatology criteria (ACR20) at week 24. Here, we report the results from the 24-week double-blind period; the open-label period with all patients receiving risankizumab is ongoing. RESULTS: At week 24, a significantly greater proportion of patients receiving risankizumab achieved the primary endpoint of ACR20 (57.3% vs placebo, 33.5%; p<0.001). Significant differences were also observed for risankizumab versus placebo for the first eight ranked secondary endpoints, including skin and nail psoriasis endpoints, minimal disease activity and resolution of enthesitis and dactylitis (p<0.001). Adverse events and serious adverse events were reported at similar rates in the risankizumab and placebo groups. Serious infections were reported for 1.0% and 1.2% of patients receiving risankizumab and placebo, respectively. There was one death in the risankizumab group (urosepsis deemed unrelated to the study drug). CONCLUSIONS: Risankizumab treatment results in significantly greater improvement of signs and symptoms of PsA compared with placebo and is well tolerated in patients with active PsA who have responded inadequately or are intolerant to ≥1 csDMARD. TRIAL REGISTRATION NUMBER: NCT03675308.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/drug therapy , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Male , Middle Aged , Treatment Outcome
14.
Ann Rheum Dis ; 81(1): 117-123, 2022 01.
Article in English | MEDLINE | ID: covidwho-1605885

ABSTRACT

OBJECTIVE: To compare the treatment efficacy and safety of tofacitinib (TOF) versus methotrexate (MTX) in Takayasu arteritis (TAK). METHODS: Fifty-three patients with active disease from an ongoing prospective TAK cohort in China were included in this study. Twenty-seven patients were treated with glucocorticoids (GCs) and TOF, and 26 patients were treated with GCs with MTX. The observation period was 12 months. Complete remission (CR), inflammatory parameter changes, GCs tapering and safety were assessed at the 6th, 9th and 12th month. Vascular lesions were evaluated at the 6th and 12th month, and relapse was analysed during 12 months. RESULTS: The CR rate was higher in the TOF group than in the MTX group (6 months: 85.19% vs 61.54%, p=0.07; 12 months: 88.46% vs 56.52%, p=0.02). During 12 months' treatment, patients in the TOF group achieved a relatively lower relapse rate (11.54% vs 34.78%, p=0.052) and a longer median relapse-free duration (11.65±0.98 vs 10.48±2.31 months, p=0.03). Average GCs dose at the 3rd, 6th and 12th month was lower in the TOF group than that in the MTX group (p<0.05). A difference was not observed in disease improvement or disease progression on imaging between the two groups (p>0.05). Prevalence of side effects was low in both groups (3.70% vs 15.38%, p=0.19). CONCLUSION: TOF was superior to MTX for CR induction, a tendency to prevent relapse and tapering of the GCs dose in TAK treatment. A good safety profile for TOF was also documented in patients with TAK.


Subject(s)
Antirheumatic Agents/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Methotrexate/therapeutic use , Piperidines/therapeutic use , Pyrimidines/therapeutic use , Takayasu Arteritis/drug therapy , Adolescent , Adult , Antirheumatic Agents/adverse effects , Disease Progression , Drug Therapy, Combination , Female , Glucocorticoids/therapeutic use , Humans , Janus Kinase Inhibitors/adverse effects , Male , Methotrexate/adverse effects , Middle Aged , Piperidines/adverse effects , Prospective Studies , Pyrimidines/adverse effects , Recurrence , Time Factors , Treatment Outcome , Young Adult
15.
Arthritis Rheumatol ; 74(2): 284-294, 2022 02.
Article in English | MEDLINE | ID: covidwho-1594369

ABSTRACT

OBJECTIVE: To evaluate seroreactivity and disease flares after COVID-19 vaccination in a multiethnic/multiracial cohort of patients with systemic lupus erythematosus (SLE). METHODS: Ninety SLE patients and 20 healthy controls receiving a complete COVID-19 vaccine regimen were included. IgG seroreactivity to the SARS-CoV-2 spike receptor-binding domain (RBD) and SARS-CoV-2 microneutralization were used to evaluate B cell responses; interferon-γ (IFNγ) production was measured by enzyme-linked immunospot (ELISpot) assay in order to assess T cell responses. Disease activity was measured by the hybrid SLE Disease Activity Index (SLEDAI), and flares were identified according to the Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI flare index. RESULTS: Overall, fully vaccinated SLE patients produced significantly lower IgG antibodies against SARS-CoV-2 spike RBD compared to fully vaccinated controls. Twenty-six SLE patients (28.8%) generated an IgG response below that of the lowest control (<100 units/ml). In logistic regression analyses, the use of any immunosuppressant or prednisone and a normal anti-double-stranded DNA antibody level prior to vaccination were associated with decreased vaccine responses. IgG seroreactivity to the SARS-CoV-2 spike RBD strongly correlated with the SARS-CoV-2 microneutralization titers and correlated with antigen-specific IFNγ production determined by ELISpot. In a subset of patients with poor antibody responses, IFNγ production was similarly diminished. Pre- and postvaccination SLEDAI scores were similar in both groups. Postvaccination flares occurred in 11.4% of patients; 1.3% of these were severe. CONCLUSION: In a multiethnic/multiracial study of SLE patients, 29% had a low response to the COVID-19 vaccine which was associated with receiving immunosuppressive therapy. Reassuringly, severe disease flares were rare. While minimal protective levels remain unknown, these data suggest that protocol development is needed to assess the efficacy of booster vaccination.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Immunocompromised Host , Immunogenicity, Vaccine , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , /therapeutic use , Adult , Antibodies, Viral/immunology , B-Lymphocytes/immunology , COVID-19 Vaccines/immunology , Case-Control Studies , Cohort Studies , Enzyme-Linked Immunospot Assay , Female , Glucocorticoids/therapeutic use , Humans , Immunoglobulin G/immunology , Interferon-gamma/immunology , Lupus Erythematosus, Systemic/immunology , Lupus Erythematosus, Systemic/physiopathology , Male , Middle Aged , Neutralization Tests , Prednisone/therapeutic use , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Symptom Flare Up
16.
Ann Rheum Dis ; 81(5): 695-709, 2022 May.
Article in English | MEDLINE | ID: covidwho-1595585

ABSTRACT

OBJECTIVES: To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD). METHODS: Physician-reported registry of I-RMD and non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively. RESULTS: The study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD). CONCLUSION: The safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.


Subject(s)
Antirheumatic Agents , COVID-19 , Musculoskeletal Diseases , Rheumatic Diseases , Aged , Antirheumatic Agents/adverse effects , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Humans , Immunosuppressive Agents/adverse effects , Male , Middle Aged , Muscular Diseases , Musculoskeletal Diseases/chemically induced , Musculoskeletal Diseases/drug therapy , Musculoskeletal Diseases/epidemiology , Registries , Rheumatic Diseases/drug therapy , Rheumatologists , SARS-CoV-2 , Vaccination/adverse effects
17.
Front Immunol ; 12: 781843, 2021.
Article in English | MEDLINE | ID: covidwho-1581326

ABSTRACT

Objectives: Vaccination against COVID-19 is highly recommended to patients affected by multiple sclerosis (MS); however, the impact of MS disease-modifying therapies (DMTs) on the immune response following vaccination has been only partially investigated. Here, we aimed to elucidate the effect of DMTs on the humoral immune response to mRNA-based anti-SARS-CoV-2 vaccines in MS patients. Methods: We obtained sera from 912 Sardinian MS patients and 63 healthy controls 30 days after the second dose of BNT162b2 vaccine and tested them for SARS-CoV-2 response using anti-Spike (S) protein-based serology. Previous SARS-CoV-2 infection was assessed by anti-Nucleocapsid (N) serology. Patients were either untreated or undergoing treatment with a total of 13 different DMTs. Differences between treatment groups comprised of at least 10 patients were assessed by generalized linear mixed-effects model. Demographic and clinical data and smoking status were analyzed as additional factors potentially influencing humoral immunity from COVID-19 vaccine. Results: MS patients treated with natalizumab, teriflunomide, azathioprine, fingolimod, ocrelizumab, and rituximab showed significantly lower humoral responses compared to untreated patients. We did not observe a statistically significant difference in response between patients treated with the other drugs (dimethyl fumarate, interferon, alemtuzumab and glatiramer acetate) and untreated patients. In addition, older age, male sex and active smoking were significantly associated with lower antibody titers against SARS-CoV-2. MS patients previously infected with SARS-CoV-2 had significantly higher humoral responses to vaccine than uninfected patients. Conclusion: Humoral response to BNT162b2 is significantly influenced by the specific DMTs followed by patients, as well as by other factors such as previous SARS-CoV-2 infection, age, sex, and smoking status. These results are important to inform targeted strategies to prevent clinically relevant COVID-19 in MS patients.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19/prevention & control , Immunogenicity, Vaccine/drug effects , Multiple Sclerosis/drug therapy , Adult , Antibodies, Viral/immunology , Female , Humans , Italy , Male , Middle Aged , SARS-CoV-2 , Seroconversion/drug effects
18.
RMD Open ; 7(3)2021 12.
Article in English | MEDLINE | ID: covidwho-1566378

ABSTRACT

OBJECTIVES: To analyse the effect of targeted therapies, either biological (b) disease-modifying antirheumatic drugs (DMARDs), targeted synthetic (ts) DMARDs and other factors (demographics, comorbidities or COVID-19 symptoms) on the risk of COVID-19 related hospitalisation in patients with inflammatory rheumatic diseases. METHODS: The COVIDSER study is an observational cohort including 7782 patients with inflammatory rheumatic diseases. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Antirheumatic medication taken immediately prior to infection, demographic characteristics, rheumatic disease diagnosis, comorbidities and COVID-19 symptoms were analysed. RESULTS: A total of 426 cases of symptomatic COVID-19 from 1 March 2020 to 13 April 2021 were included in the analyses: 106 (24.9%) were hospitalised and 19 (4.4%) died. In multivariate-adjusted models, bDMARDs and tsDMARDs in combination were not associated with hospitalisation compared with conventional synthetic DMARDs (OR 0.55, 95% CI 0.24 to 1.25 of b/tsDMARDs, p=0.15). Tumour necrosis factor inhibitors (TNF-i) were associated with a reduced likelihood of hospitalisation (OR 0.32, 95% CI 0.12 to 0.82, p=0.018), whereas rituximab showed a tendency to an increased risk of hospitalisation (OR 4.85, 95% CI 0.86 to 27.2). Glucocorticoid use was not associated with hospitalisation (OR 1.69, 95% CI 0.81 to 3.55). A mix of sociodemographic factors, comorbidities and COVID-19 symptoms contribute to patients' hospitalisation. CONCLUSIONS: The use of targeted therapies as a group is not associated with COVID-19 severity, except for rituximab, which shows a trend towards an increased risk of hospitalisation, while TNF-i was associated with decreased odds of hospitalisation in patients with rheumatic disease. Other factors like age, male gender, comorbidities and COVID-19 symptoms do play a role.


Subject(s)
Antirheumatic Agents , COVID-19 , Rheumatic Diseases , Antirheumatic Agents/adverse effects , Humans , Male , Rheumatic Diseases/drug therapy , Rheumatic Diseases/epidemiology , SARS-CoV-2
19.
Arthritis Care Res (Hoboken) ; 74(5): 733-740, 2022 May.
Article in English | MEDLINE | ID: covidwho-1565158

ABSTRACT

OBJECTIVE: We aimed to assess trends in anxiety and interruptions in disease-modifying antirheumatic drug (DMARD) use among patients with rheumatic diseases during the COVID-19 pandemic and to evaluate whether DMARD interruptions were associated with disease flares. METHODS: ArthritisPower, the Vasculitis Patient-Powered Research Network, and other patient organizations invited members to join a 52-week longitudinal study, with baseline surveys completed March 29 to June 30, 2020, with follow-up through May 2021. Logistic regression incorporating generalized estimating equations evaluated associations between interruptions in DMARD use and self-reported disease flares at the next survey, adjusting for demographic characteristics, medications, disease, and calendar time. RESULTS: Among 2,424 patients completing a median of 5 follow-up surveys, the mean age was 57 years, 87% were female, and the most common conditions were rheumatoid arthritis, vasculitis, and psoriatic arthritis. Average Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety T scores decreased from April 2020 (58.7) to May 2021 (53.7) (P < 0.001 for trend). Interruptions in DMARD use decreased from April (11.2%) to December 2020 (7.5%) (P < 0.001) but increased through May 2021 (14.0%) (P < 0.001). Interruptions in DMARD use were associated with a significant increase in severe flares (rated ≥6 of 10) at the next survey (12.9% versus 8.0% [odds ratio (OR) 1.71 (95% confidence interval [95% CI 1.23, 2.36]) although not any flare (OR 1.18 [95% CI 0.89, 1.58])]. CONCLUSION: Anxiety and interruptions in DMARD use initially decreased over time, but DMARD interruptions increased during 2021, possibly related to an increase in COVID-19 cases or vaccine availability. Interruptions in DMARD use were associated with increased rates of severe disease flares, highlighting the importance of avoiding unnecessary DMARD interruptions.


Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , COVID-19 , Vasculitis , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/epidemiology , COVID-19/epidemiology , Female , Humans , Longitudinal Studies , Male , Middle Aged , Pandemics , Symptom Flare Up , Vasculitis/drug therapy
20.
RMD Open ; 7(3)2021 12.
Article in English | MEDLINE | ID: covidwho-1561469

ABSTRACT

BACKGROUND: The persistence of the SARS-CoV2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Questions remain as to which cohorts require SARS-CoV2 boosters. However, there is a critical lack of data on the dynamics of vaccine responses in patients with chronic inflammatory diseases (CID) undergoing immunosuppressive/disease modifying anti-rheumatic (DMARD) treatment. Here, we present the first data regarding the decline of the vaccine-induced humoral immune responses in patients with CID. METHODS: 23 patients with CID were monitored clinically and for anti-spike IgG and IgA levels, neutralization efficacy and antigen-specific CD4+ T cell responses over the first 6 months after SARS-CoV2 vaccination. 24 healthy individuals were included as controls. RESULTS: While anti-spike IgG-levels declined in CID patients and healthy controls, patients receiving anti-TNF treatment showed significantly greater declines at 6 months post second vaccination in IgG and especially neutralizing antibodies. IgA levels were generally lower in CID patients, particularly during anti-TNF therapy. No differences in SARS-CoV2 spike-specific CD4+ T-cell frequencies were detected. CONCLUSION: Although the long-term efficacy of SARS-CoV2 vaccination in CID patients undergoing disease-modifying therapy is still not known, the pronounced declines in humoral responses towards SARS-CoV2 6 months after mRNA vaccination in the context of TNF blockade should be considered when formulating booster regimens. These patients should be considered for early booster vaccinations.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 , Immunity, Humoral , Tumor Necrosis Factor Inhibitors/adverse effects , Antibodies, Viral/blood , Antirheumatic Agents/adverse effects , COVID-19/immunology , COVID-19/prevention & control , Humans , Immunosuppressive Agents/adverse effects
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