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1.
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
2.
Sci Rep ; 12(1): 465, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1627057

ABSTRACT

We conducted retrospective cohort studies of patients with relapsing polychondritis (RP) twice in 2009 and 2019, using a physician questionnaire. We compared the patients' clinical statuses between the years. Age and gender were comparable between the two surveys. Mean disease duration was longer in 2019 survey (8.3 years) than that in 2009 survey (4.8 years, P < 0.001). The mortality rate declined in 2019 survey compared with those in 2009 survey (from 9.2 to 1.6%, P < 0.001). Incidence of airway involvement decreased in 2019 survey compared with that in 2009 survey (from 49 to 37%, P = 0.012). In 2019 survey, we found more frequent use of biological agents and immunosuppressants in patients with airway involvement. When we focused on RP patients with airway involvement, physicians in 2019 chose methotrexate and calcineurin inhibitors preferentially, compared with azathioprine and cyclophosphamide. Of note is that increased use of infliximab was observed in RP patients with airway involvement, but not in those without. Reduction of airway involvement and mortality in patients with RP was observed in 2019 survey. The reduction may associate with the frequent use of biologics including infliximab in RP patients with airway involvement.


Subject(s)
Polychondritis, Relapsing/complications , Polychondritis, Relapsing/drug therapy , Respiratory Tract Diseases/etiology , Adult , Azathioprine/therapeutic use , Cross-Sectional Studies , Cyclophosphamide/therapeutic use , Female , Humans , Immunosuppressive Agents/therapeutic use , Infliximab/therapeutic use , Japan/epidemiology , Male , Methotrexate/therapeutic use , Middle Aged , Polychondritis, Relapsing/epidemiology , Polychondritis, Relapsing/mortality , Respiratory Tract Diseases/epidemiology , Respiratory Tract Diseases/mortality , Retrospective Studies , Surveys and Questionnaires
4.
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
5.
J Autoimmun ; 125: 102743, 2021 12.
Article in English | MEDLINE | ID: covidwho-1568811

ABSTRACT

OBJECTIVES: To investigate humoral responses and safety of mRNA SARS-CoV-2 vaccines in systemic autoimmune and autoinflammatory rheumatic disease (SAARD) patients subjected or not to treatment modifications during vaccination. METHODS: A nationwide, multicenter study, including 605 SAARD patients and 116 controls, prospectively evaluated serum anti-SARS-CoV-2 S1-protein IgG antibody titers, side-effects, and disease activity, one month after complete vaccination, in terms of distinct treatment modification strategies (none, partial and extended modifications). Independent risk factors associated with hampered humoral responses were identified by data-driven multivariable logistic regression analysis. RESULTS: Patients with extended treatment modifications responded to vaccines similarly to controls as well as SAARD patients without immunosuppressive therapy (97.56% vs 100%, p = 0.2468 and 97.56% vs 97.46%, p > 0.9999, respectively). In contrast, patients with partial or without therapeutic modifications responded in 87.50% and 84.50%, respectively. Furthermore, SAARD patients with extended treatment modifications developed higher anti-SARS-CoV-2 antibody levels compared to those without or with partial modifications (median:7.90 vs 7.06 vs 7.1, p = 0.0003 and p = 0.0195, respectively). Mycophenolate mofetil (MMF), rituximab (RTX) and methotrexate (MTX) negatively affected anti-SARS-CoV-2 humoral responses. In 10.5% of vaccinated patients, mild clinical deterioration was noted; however, no differences in the incidence of deterioration were observed among the distinct treatment modification SAARD subgroups. Side-effects were generally comparable between SAARD patients and controls. CONCLUSIONS: In SAARD patients, mRNA SARS-CoV-2 vaccines are effective and safe, both in terms of side-effects and disease flares. Treatment with MMF, RTX and/or MTX compromises anti-SARS-CoV-2 antibody responses, which are restored upon extended treatment modifications without affecting disease activity.


Subject(s)
/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Autoimmune Diseases/immunology , Hereditary Autoinflammatory Diseases/immunology , Rheumatic Diseases/immunology , /adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Autoimmune Diseases/drug therapy , COVID-19/prevention & control , Female , Greece , Hereditary Autoinflammatory Diseases/drug therapy , Humans , Immunoglobulin G/blood , Male , Methotrexate/adverse effects , Methotrexate/therapeutic use , Middle Aged , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Prospective Studies , Rheumatic Diseases/drug therapy , Rituximab/adverse effects , Rituximab/therapeutic use , SARS-CoV-2/immunology , Young Adult
6.
Int Immunopharmacol ; 101(Pt B): 108324, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1549850

ABSTRACT

BACKGROUND: During the ongoing COVID-19 pandemic, immunocompromised patients are at a higher risk of severe infection, since the immune system has an important role in defeating this disease. This study compares the severity of COVID-19 in patients taking methotrexate with the severity of their family members' illness as patients with normal immune system function. METHODS: A total of 35 participants, including 14 patients taking methotrexate and 21 patients with normal immune function, entered this study, and the indicators of COVID-19 severity were compared between these two groups. RESULTS: The case group, who were on methotrexate therapy, had significantly less severe COVID-19 based on their symptoms, including fever (p = 0.000) and cough and dyspnea (p = 0.01) as well as in terms of COVID-19 severity indicators such as pulmonary involvement (p = 0.001), ferritin level (p = 0.001), white blood cell count (p = 0.008) and CRP level (p = 0.006), compared to the control group. There was a significant correlation between taking methotrexate and lower severity in COVID-19 disease. CONCLUSION: The present findings demonstrated that methotrexate does not predispose patients to severe COVID-19; on the contrary, patients taking methotrexate may experience a milder disease, possibly due to their reduced severe inflammatory reactions as a result of inhibited TNFα, lowered IL6, and increased T regulatory cells. According to these findings, methotrexate appears to be a suitable treatment option for patients who need immunosuppressive medications during the COVID-19 pandemic.


Subject(s)
COVID-19/drug therapy , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , SARS-CoV-2 , Adolescent , Adult , COVID-19/epidemiology , Female , Humans , Male , Pandemics , Retrospective Studies , Severity of Illness Index , Young Adult
7.
Pediatr Rheumatol Online J ; 19(1): 163, 2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1542116

ABSTRACT

BACKGROUND: Flares of juvenile idiopathic arthritis (JIA) have been described in the context of various infections. Flares of rheumatic diseases in adults have been described following infection with SARS-CoV-2 in several cohorts. So far, the effect of infection with SARS-CoV-2 on the course of JIA is unknown. METHODS: The database of the German Center for Pediatric and Adolescent Rheumatology was searched for patients with confirmed infection with SARS-CoV-2 and subsequent disease flare, admitted from July 2020 until June 2021. cJADAS-27, ESR and C-reactive protein, as well as uveitis activity, medication at the time of flare and treatment of flare was extracted. Patient cases were described individually. RESULTS: Out of 988 patients admitted, five patients with remission off medication (n = 2) or inactive disease on medication (n = 3) were identified, with flare symptoms up to four weeks after infection with SARS-CoV-2. CONCLUSIONS: Flares can occur after infection with SARS-CoV-2 in patients with JIA in remission or inactive disease on medication. Treating physicians need to be aware of this fact, especially when counseling patients with rheumatic diseases about the respective dangers of COVID-19 and vaccination against SARS-CoV-2.


Subject(s)
Arthritis, Juvenile/physiopathology , COVID-19/physiopathology , Symptom Flare Up , Adolescent , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Juvenile/complications , Arthritis, Juvenile/drug therapy , Arthritis, Juvenile/metabolism , Azetidines/therapeutic use , Blood Sedimentation , C-Reactive Protein/metabolism , COVID-19/complications , Child , Etanercept/therapeutic use , Female , Humans , Male , Methotrexate/therapeutic use , Purines/therapeutic use , Pyrazoles/therapeutic use , Remission Induction , SARS-CoV-2 , Sulfonamides/therapeutic use , Uveitis/complications , Uveitis/physiopathology
8.
BMC Musculoskelet Disord ; 22(1): 953, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1526624

ABSTRACT

BACKGROUND: Hand osteoarthritis is a common and disabling problem without effective therapies. Accumulating evidence suggests the role of local inflammation in causing pain and structural progression in hand osteoarthritis, and hand osteoarthritis with synovitis is a commonly encountered clinical phenotype. Methotrexate is a well-established, low-cost, and effective treatment for inflammatory arthritis with a well-described safety profile. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether methotrexate reduces pain over 6 months in patients with hand osteoarthritis and synovitis. METHODS: Ninety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 months. The secondary outcomes include changes in physical function and quality of life assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, Short-Form-36, tender and swollen joint count, and grip strength, and structural progression assessed using progression of synovitis and bone marrow lesions from magnetic resonance imaging and radiographic progression at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups. DISCUSSION: This study will provide high-quality evidence to address whether methotrexate has an effect on reducing pain over 6 months in patients with hand osteoarthritis and synovitis, with major clinical and public health importance. While a positive trial will inform international clinical practice guidelines for the management of hand osteoarthritis, a negative trial would be highly topical and change current trends in clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124.


Subject(s)
Osteoarthritis , Synovitis , Australia , Canada , Double-Blind Method , Humans , Methotrexate/therapeutic use , Multicenter Studies as Topic , Osteoarthritis/diagnostic imaging , Osteoarthritis/drug therapy , Quality of Life , Randomized Controlled Trials as Topic , Synovitis/diagnostic imaging , Synovitis/drug therapy , Treatment Outcome
9.
Mod Rheumatol Case Rep ; 5(2): 226-228, 2021 07.
Article in English | MEDLINE | ID: covidwho-1493585

ABSTRACT

We report the case of a 61-year old female with a 20-year history of seropositive rheumatoid arthritis (RA) who developed acute hepatitis. Her arthritis had been treated with methotrexate (MTX) since 2003 and, following an increase in disease activity, Rituximab (RTX) was commenced in January 2017. In May 2020, routine blood tests showed a new elevation in her liver profile, although synthetic function was preserved. A standard liver screen found no cause for her acutely abnormal lab values. Upon additional serological testing, the patient was confirmed to have acute hepatitis E virus (HEV). Her primary complaint at the time was fatigue. Within a month, her liver blood tests spontaneously improved and her symptoms resolved with conservative management.


Subject(s)
Arthritis, Rheumatoid , Hepatitis E , Immunocompromised Host , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Female , Hepatitis E/diagnosis , Hepatitis E/immunology , Humans , Methotrexate/therapeutic use , Middle Aged , Rituximab/therapeutic use
10.
Inflammation ; 45(1): 172-179, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1474041

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19) is associated with uncontrolled inflammatory responses. Loss of pulmonary angiotensin-converting enzyme 2 (ACE2) function has been associated with SARS-CoV-2 infection. The aberrant signalling and dysregulated inflammation characteristic of lung cancer have marked similarities with SARS-CoV-2 infection. Spearman's correlation analysis of The Cancer Genome Atlas (TCGA) datasets indicated an inverse correlation between ACE2 and IL6 in lung adenocarcinoma. qRT-PCR analysis revealed CoV-2-SRBD-mediated diminished ACE2 expression in lung cancer cells that was concomitant with increased IL6 expression. Western blot and qRT-PCR analysis suggested that treatment with methotrexate (MTx) dampened CoV-2-SRBD-mediated increase in JAK1/STAT3 phosphorylation, gp130, IL6, and folate-binding protein (FBP) expressions. MTx also rescued the diminished expression of ACE2 in CoV-2-SRBD transfected cells. As lung tissue injury in severely affected COVID-19 patients is characterised by aberrant inflammatory response, repurposing MTx as an effective therapy against critical regulators of inflammation in SARS-CoV-2 infection warrants investigation.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , Glycyrrhizic Acid/therapeutic use , Immunosuppressive Agents/therapeutic use , Interleukin-6/biosynthesis , Methotrexate/therapeutic use , A549 Cells , Adenocarcinoma of Lung/pathology , Anti-Inflammatory Agents/therapeutic use , COVID-19/immunology , COVID-19/pathology , Cell Line, Tumor , Cytokine Receptor gp130/biosynthesis , Folate Receptor 2/biosynthesis , HMGB1 Protein/antagonists & inhibitors , HMGB1 Protein/metabolism , Humans , Interleukin-6/immunology , Janus Kinase 1/metabolism , Lung Neoplasms/pathology , Phosphorylation/drug effects , SARS-CoV-2/drug effects , STAT3 Transcription Factor/metabolism , Spike Glycoprotein, Coronavirus/immunology
11.
Bioorg Med Chem ; 48: 116389, 2021 10 15.
Article in English | MEDLINE | ID: covidwho-1427706

ABSTRACT

With the emergence of the third infectious and virulent coronavirus within the past two decades, it has become increasingly important to understand how the virus causes infection. This will inform therapeutic strategies that target vulnerabilities in the vital processes through which the virus enters cells. This review identifies enzymes responsible for SARS-CoV-2 viral entry into cells (ACE2, Furin, TMPRSS2) and discuss compounds proposed to inhibit viral entry with the end goal of treating COVID-19 infection. We argue that TMPRSS2 inhibitors show the most promise in potentially treating COVID-19, in addition to being a pre-existing medication with fewer predicted side-effects.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Janus Kinase Inhibitors/therapeutic use , SARS-CoV-2/drug effects , Animals , Drug Combinations , Humans , Methotrexate/therapeutic use , Receptors, Angiotensin/metabolism , Signal Transduction/drug effects
13.
Ann Rheum Dis ; 80(9): 1158-1167, 2021 09.
Article in English | MEDLINE | ID: covidwho-1356912

ABSTRACT

OBJECTIVES: Although causality remains to be established, targeting dysbiosis of the intestinal microbiota by faecal microbiota transplantation (FMT) has been proposed as a novel treatment for inflammatory diseases. In this exploratory, proof-of-concept study, we evaluated the safety and efficacy of FMT in psoriatic arthritis (PsA). METHODS: In this double-blind, parallel-group, placebo-controlled, superiority trial, we randomly allocated (1:1) adults with active peripheral PsA (≥3 swollen joints) despite ongoing treatment with methotrexate to one gastroscopic-guided FMT or sham transplantation into the duodenum. Safety was monitored throughout the trial. The primary efficacy endpoint was the proportion of participants experiencing treatment failure (ie, needing treatment intensification) through 26 weeks. Key secondary endpoints were change in Health Assessment Questionnaire Disability Index (HAQ-DI) and American College of Rheumatology (ACR20) response at week 26. RESULTS: Of 97 screened, 31 (32%) underwent randomisation (15 allocated to FMT) and 30 (97%) completed the 26-week clinical evaluation. No serious adverse events were observed. Treatment failure occurred more frequently in the FMT group than in the sham group (9 (60%) vs 3 (19%); risk ratio, 3.20; 95% CI 1.06 to 9.62; p=0.018). Improvement in HAQ-DI differed between groups (0.07 vs 0.30) by 0.23 points (95% CI 0.02 to 0.44; p=0.031) in favour of sham. There was no difference in the proportion of ACR20 responders between groups (7 of 15 (47%) vs 8 of 16 (50%)). CONCLUSIONS: In this first preliminary, interventional randomised controlled trial of FMT in immune-mediated arthritis, we did not observe any serious adverse events. Overall, FMT appeared to be inferior to sham in treating active peripheral PsA. TRIAL REGISTRATION NUMBER: NCT03058900.


Subject(s)
Arthritis, Psoriatic/therapy , Dysbiosis/therapy , Fecal Microbiota Transplantation/methods , Adult , Antirheumatic Agents/therapeutic use , Arthritis, Psoriatic/microbiology , Female , Humans , Male , Methotrexate/therapeutic use , Middle Aged , Proof of Concept Study , Treatment Outcome
15.
Clin Dermatol ; 39(1): 76-83, 2021.
Article in English | MEDLINE | ID: covidwho-1300693

ABSTRACT

As of July 9, 2020, there were more than 12 million confirmed cases of coronavirus disease 2019 (COVID-19) across the globe, with more than 550,000 deaths. Many European countries, including Belgium, the United Kingdom, Italy, and Spain, have had the highest numbers of fatalities per capita. This indicates the potential for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to overwhelm even the most advanced health care systems despite extreme societal interventions. Since its emergence, SARS-CoV-2 has disseminated across the globe, affecting the structure of global societies, infrastructure, and economies. Patients with alopecia are a diverse group who, for various indications, are prescribed a number of antimicrobials and antiandrogen treatments in addition to immunomodulatory therapies such as hydroxychloroquine, oral corticosteroids, and a range of broad immunosuppressants. These drugs are being scrutinized for their capacity to potentially affect SARS-CoV-2 outcomes. We examine these treatments and highlight the critical role that patient registries will play in generating real-world evidence to assess their impact on COVID-19 outcomes.


Subject(s)
Alopecia/drug therapy , COVID-19/drug therapy , Alopecia/classification , Androgen Antagonists/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antimalarials/therapeutic use , Cyclosporine/therapeutic use , Glucocorticoids/therapeutic use , Humans , Hydroxychloroquine/therapeutic use , Immunosuppressive Agents/therapeutic use , Janus Kinase Inhibitors/therapeutic use , Methotrexate/therapeutic use , Prognosis , Registries , SARS-CoV-2
16.
Transfus Apher Sci ; 60(5): 103200, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1284583

ABSTRACT

Psoriasis is a chronic inflammatory skin disease that is characterized by well-demarcated erythematous plaques with a silver scale. Although many new and emerging therapeutic agents are often sufficient to control the disease, there is still a need for alternative treatment options in challenging cases. Extracorporeal photopheresis (ECP) has been applied to many T-cell-mediated diseases to restore immune homeostasis and treat psoriasis effectively. In this paper, we present a psoriasis patient who did not respond to methotrexate, narrowband ultraviolet B, or acitretin. Because of a diagnosis of non-Hodgkin lymphoma, the patient had contraindications for cyclosporine, fumaric acid esters, and biologics but achieved remission with a total of 12 sessions of ECP in two and a half months. Although exacerbation was recorded after polymerase chain reaction (PCR) confirmed coronavirus 2019 (COVID-19) disease infection at the end of the first month, scores from the psoriasis area severity index (PASI) and dermatological life quality index (DLQI) were regressed significantly within two and a half months. ECP seems to provide an effective and rapid response for psoriasis and should be considered for psoriasis patients who fail to respond or have contraindications to existing treatments.


Subject(s)
COVID-19/complications , Lymphoma, Non-Hodgkin/complications , Pandemics , Photopheresis , Psoriasis/drug therapy , SARS-CoV-2 , Acitretin/therapeutic use , Chemical and Drug Induced Liver Injury/etiology , Combined Modality Therapy , Contraindications, Drug , Cyclosporine/adverse effects , Humans , Male , Methotrexate/adverse effects , Methotrexate/therapeutic use , Middle Aged , Nails/pathology , Psoriasis/complications , Psoriasis/pathology , Psoriasis/radiotherapy , Quality of Life , Severity of Illness Index , Ultraviolet Therapy
18.
Am J Clin Dermatol ; 22(5): 709-718, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1248759

ABSTRACT

BACKGROUND: The impact of immune-related conditions on the outcomes of coronavirus disease 2019 (COVID-19) is poorly understood. Determinants of COVID-19 outcomes among patients with psoriasis are yet to be established. OBJECTIVE: Th objective of this study was to characterize a large cohort of patients with psoriasis with COVID-19 and to identify predictors of COVID-19-associated hospitalization and mortality. METHODS: A population-based nested case-control study was performed using the computerized database of Clalit Health Services, Israel. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence (CIs) of predictors for COVID-19-associated hospitalization and mortality. RESULTS: The study population included 3151 patients with psoriasis who tested positive for COVID-19. Subclinical COVID-19 infection occurred in 2818 (89.4%) of the patients while 122 (3.9%), 71 (2.3%), 123 (3.9%), and 16 (0.5%) of the patients experienced a mild, moderate, severe, and critical disease, respectively. Overall, 332 (10.5%) patients were hospitalized and 50 (1.6%) patients died because of COVID-19 complications. Intake of methotrexate independently predicted COVID-19-associated hospitalization (adjusted OR 2.30; 95% CI 1.11-4.78; p = 0.025). Use of biologic agents was not associated with COVID-19-associated hospitalization (OR 0.75; 95% CI 0.32-1.73; p = 0.491) or mortality (OR 0.85; 95% CI 0.12-6.21; p = 0.870). Older age, the presence of comorbid cardiovascular diseases, metabolic syndrome, chronic obstructive pulmonary disease, and chronic renal failure independently predicted both COVID-19-associated hospitalization and mortality. CONCLUSIONS: The use of oral methotrexate was associated with an increased odds of COVID-associated hospitalization, whereas the use of biologic drugs was not associated with worse outcomes of COVID-19 among patients with psoriasis.


Subject(s)
Biological Products/therapeutic use , COVID-19/mortality , Hospitalization/statistics & numerical data , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Psoriasis/drug therapy , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Case-Control Studies , Child , Child, Preschool , Comorbidity , Female , Humans , Infant , Male , Middle Aged , Psoriasis/epidemiology , Risk Factors , SARS-CoV-2 , Young Adult
19.
CNS Drugs ; 35(3): 317-330, 2021 03.
Article in English | MEDLINE | ID: covidwho-1141535

ABSTRACT

BACKGROUND: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) target immunity and have the potential to increase the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and alter its clinical course. We assessed these risks in patients with MS (PwMS). OBJECTIVE: The objective of this study was to describe the overall risk of coronavirus disease 2019 (COVID-19) infection, severe disease course, and potential population-level predictors of COVID-19 infection in PwMS, and to provide a context using a cohort of patients with systemic lupus erythematosus (SLE). In addition, the association of different MS DMTs with the incidence and clinical course of COVID-19 was evaluated. Safety data from the Biogen Global Safety Database are also presented on reported cases of COVID-19 in patients treated with Biogen MS therapies. METHODS: The IBM® Explorys electronic health record database of > 72,000,000 patients from US healthcare networks identified patients with MS or SLE, with and without polymerase chain reaction-confirmed COVID-19. COVID-19 cumulative incidence, hospitalization, and deaths among DMT classes were compared using logistic regression (adjusted for age, sex, body mass index, comorbidities, and race/ethnicity). As a secondary data source to assess safety data, COVID-19 reports for Biogen MS therapies were extracted and described from Biogen's Global Safety Database. RESULTS: 30,478 PwMS with an open DMT prescription were identified within Explorys; 344 were COVID-19 positive. The most significant risk factors for acquiring COVID-19 were comorbidity score ≥ 1, body mass index ≥ 30, and Black/African ancestry. Similar risk factors were also identified for patients with SLE. Patients with MS were less likely to develop COVID-19 when treated with interferons (0.61%) and glatiramer acetate (0.51%), vs all other MS DMTs (both p < 0.001); anti-CD20 therapy was associated with the highest risk (3.45%; p < 0.0001). In the Biogen Global Safety Database, we identified 1217 patients who were COVID-19 positive treated with intramuscular interferon beta-1a, peginterferon beta-1a, natalizumab, dimethyl fumarate, diroximel fumarate, or fampridine. CONCLUSIONS: Comorbidities, obesity, and Black/African ancestry, but not age, were associated with a higher risk of SARS-CoV-2 infection in PwMS. Interferons and glatiramer acetate were associated with a reduced COVID-19 risk, whereas anti-CD20 therapies were associated with an increased risk, within the treated MS cohort. COVID-19 safety reports for patients receiving Biogen MS therapies were consistent with the Explorys database and MS literature, illustrating the replicability and power of this approach.


Subject(s)
COVID-19/epidemiology , Hospitalization/statistics & numerical data , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/drug therapy , Adolescent , Adult , African Americans/statistics & numerical data , Aged , Aged, 80 and over , Alemtuzumab/therapeutic use , Azathioprine/therapeutic use , COVID-19/mortality , Cladribine/therapeutic use , Comorbidity , Crotonates/therapeutic use , Cyclophosphamide/therapeutic use , Cyclosporine/therapeutic use , Databases, Factual , Dimethyl Fumarate/therapeutic use , Female , Fingolimod Hydrochloride/therapeutic use , Humans , Hydroxybutyrates , Immunologic Factors/therapeutic use , Incidence , Interferon-beta/therapeutic use , Logistic Models , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/epidemiology , Male , Methotrexate/therapeutic use , Middle Aged , Mitoxantrone/therapeutic use , Multiple Sclerosis/epidemiology , Mycophenolic Acid/therapeutic use , Natalizumab/therapeutic use , Nitriles , Obesity/epidemiology , Risk Factors , Rituximab/therapeutic use , SARS-CoV-2 , Toluidines/therapeutic use , United States/epidemiology , Young Adult
20.
Eur J Obstet Gynecol Reprod Biol ; 259: 95-99, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1103850

ABSTRACT

OBJECTIVE: During the 2020 COVID-19 pandemic there was a decrease in emergency room arrivals. There is limited evidence about the effect of this change in behavior on women's health. We aimed to evaluate the impact of the COVID-19 pandemic on the diagnosis, treatment and complications of women presenting with a tubal Ectopic Pregnancy (EP). STUDY DESIGN: This is a single centre retrospective cohort study. We compared the clinical presentation, treatment modalities and complications of all women presenting in our institution with a tubal EP during the COVID-19 pandemic between 15 March and 15 June 2020, with women who were treated in our institution with the same diagnosis in the corresponding period for the years 2018-2019. RESULTS: The study group included 19 cases of EP (N = 19) that were treated between the 15 March 2020 and 15 June 2020. The control group included 30 cases of EP (N = 30) that were admitted to in the corresponding period during 2018 and 2019. Maternal age, parity, gravity and mode of conception (natural vs. assisted) were similar between the two groups. There was no difference in the mean gestational age (GA) according to the last menstrual period. In the study group more women presented with sonographic evaluation of high fluid volume in the abdomen than in the control group (53 % vs 17 %, P value 0.01). This finding is correlated with a more advanced disease status. In the study group there was a highly statistically significant 3-fold increase in rupture among cases (P < 0.005) and a 4-fold larger volume of blood in the entrance to the abdomen (P < 0.002). We found that there were no cases of ruptured EP in the group of women who were pregnant after assisted reproduction. CONCLUSION: We found a higher rate of ruptured ectopic pregnancies in our institution during the COVID-19 pandemic. Health care providers should be alerted to this collateral damage in the non-infected population during the COVID-19 pandemic.


Subject(s)
COVID-19 , Pregnancy, Tubal/epidemiology , Abdominal Pain/physiopathology , Abortifacient Agents, Nonsteroidal/therapeutic use , Adult , Chorionic Gonadotropin, beta Subunit, Human/blood , Cohort Studies , Delayed Diagnosis , Female , Humans , Israel/epidemiology , Laparoscopy , Methotrexate/therapeutic use , Pregnancy , Pregnancy, Tubal/diagnosis , Pregnancy, Tubal/physiopathology , Pregnancy, Tubal/therapy , Reproductive Techniques, Assisted , Retrospective Studies , Rupture, Spontaneous/epidemiology , SARS-CoV-2 , Salpingectomy , Ultrasonography, Prenatal , Uterine Hemorrhage/physiopathology
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