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BMC Rheumatology Jun 2024Vaccines are a crucial component of the global efforts to control the spread of COVID-19. Very little is known about COVID-19 vaccine responses in patients living with...
BACKGROUND
Vaccines are a crucial component of the global efforts to control the spread of COVID-19. Very little is known about COVID-19 vaccine responses in patients living with autoimmune rheumatic conditions in Africa. We examined the clinical reaction to COVID-19 vaccinations in Ghanaians diagnosed with autoimmune rheumatic disease.
METHODS
This was a hospital-based interventional cohort study of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients recruited via regular face-to-face clinic visits. The systemic lupus erythematosus disease activity index Selena modification (SELENA-SLEDAI) and the disease activity score 28-joint count-erythrocyte sedimentation rate (DAS28-ESR) were used to measure changes in disease activity levels.
RESULTS
Thirty-eight (38) patients of which 21 (55.3%) were diagnosed with SLE and 17 (44.7%) with RA contributed data for analyses. Most (89.5%) of the patients were females, with a mean age of 37.4 years. The SLE patients experienced a notable increase in severe flares during weeks three and six, as well as the third and sixth months, followed by subsequent decreases in the twelfth month, while remission levels increased throughout the same period. Among RA patients, high disease activity decreased during weeks three and six, as well as the third, sixth, and twelfth months, with remission levels increasing during the same time. A low dose (≥ 50 < 75 mg) dose of azathioprine was at some point associated with having a severe flare among SLE patients. After both vaccine doses, SLE patients were the majority having experienced both local and systemic reactions, all resolving within 24 h. Approximately 73.7% of the patients were COVID-19 negative at baseline. During post-vaccination visits, this increased to 100% by week six, with no positives thereafter.
CONCLUSION
This study explores COVID-19 vaccine responses in Ghanaian autoimmune rheumatic disease patients, revealing disease activity levels in RA patients improved after vaccination compared to SLE patients. Our findings identify a potential link between low-dose azathioprine and severe flares in SLE patients, particularly evident in the third-week post-vaccination. Further research is warranted to clarify these findings and guide tailored treatment approaches in this medically significant population during pandemics and vaccination efforts.
PubMed: 38880913
DOI: 10.1186/s41927-024-00396-5 -
BMC Neurology Jun 2024We present a rare case of NeuroBehcet's-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of... (Review)
Review
BACKGROUND
We present a rare case of NeuroBehcet's-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of NeuroBehcet's. In addition, we describe the novel use of subcutaneous tocilizumab for this indication. This is followed by a review of the literature on this topic.
CASE
The patient was a 28-year-old lady of Southern Chinese origin with a known history of Behcet's disease with oral ulcers and ocular findings for which she was on mycophenolate mofetil and adalimumab. She presented with a headache and bilateral disc swelling associated with an intracranial pressure (ICP) of > 40cmH20. There were no structural lesions or cerebral venous thrombosis (CVT) on imaging. Initial lumbar puncture had raised leucocytes and protein. We discuss diagnostic challenges given persistently elevated ICP despite subsequent non-inflammatory cerebrospinal fluid (CSF) profiles and non-response to acetazolamide. She eventually showed a response to immunosuppressant therapy in the form of pulsed methylprednisolone, cyclophosphamide and subsequently subcutaneous tocilizumab, supporting the diagnosis of NBrIHwCVT. Complete normalization of ICP remains challenging. Her disease course was severe, unusual for her ethnicity.
LITERATURE REVIEW
We identified 34 patients (including ours) from 14 publications. We found that the majority of NBrIHwCVT patients were young (average age of 34 years), with a slight female preponderance. Of the 17 cases in the literature with available data on CSF profile, none had raised leucocytes whilst one patient had elevated protein. Patients were generally treated with steroids and occasionally azathioprine, in line with the suspected autoimmune pathophysiology. Of 22 patients with data on outcome, six (27%) were noted to have recurrence of symptoms generally occurring a few months later.
CONCLUSION
As demonstrated by this case, NBrIHwCVT can present with BD with raised ICP even if there is no prior history of NB, central Asian ethnicity, cerebral venous thrombosis or features of inflammation on the CSF. We demonstrated how novel use of Tocilizumab may have a role in the management of NBrIHwCVT. Based on our literature review, patients were more likely to be young, female, display a non-inflammatory CSF picture, be treated with steroids and harbour a possibility of recurrence.
Topics: Humans; Female; Adult; Intracranial Hypertension; Behcet Syndrome; Antibodies, Monoclonal, Humanized; Immunosuppressive Agents
PubMed: 38877431
DOI: 10.1186/s12883-024-03708-x -
Digestive Diseases and Sciences Jun 2024Patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) commonly experience immunogenic loss of response (LOR) by formation of anti-drug antibodies...
BACKGROUND AND AIMS
Patients with inflammatory bowel disease (IBD) receiving infliximab (IFX) commonly experience immunogenic loss of response (LOR) by formation of anti-drug antibodies (ADAs). An immunomodulator (IMM) used in combination with initial IFX induction is known to reduce ADA development and improve clinical outcomes. We aimed to assess the impact of reactively adding an IMM to patients on IFX monotherapy.
METHODS
We conducted a retrospective cohort study and systematic review with meta-analysis of patients with IBD demonstrating immunologic LOR, with or without clinical LOR, that had an IMM (azathioprine, 6-mercaptopurine, or methotrexate) reactively added (reactive combination therapy; rCT) to combat elevated ADAs and raise IFX level. Data were extracted for pooled effect size estimation using random-effects models, and ADA and IFX trough levels were compared pre- and post-IMM initiation.
RESULTS
We identified 6 patients who received rCT due to rising ADA titers and low IFX levels. Median ADA titer decreased from 506 ng/mL (interquartile range (IQR) [416-750]) to 76.5 ng/mL (IQR [25.8-232]), an 85% decrease (p = 0.031). Median IFX trough increased from 0.4 µg/mL (IQR [0.4-0.48]) to 8.25 µg/mL (IQR [3.7-9.6]), a 20.6-fold increase (p = 0.038). Meta-analysis pooled effect size of 7 studies with 89 patients showed an 87% ADA titer reduction [95% confidence interval (CI) = 72-94%], 6.7-fold increased IFX trough (95% CI = 2.4-18.7), and 76% clinical remission rescue rate (95% CI = 59-93%).
CONCLUSIONS
These results suggest rCT is a valid rescue strategy in patients with immunogenic LOR to IFX to reduce ADA titers, restore therapeutic IFX levels, and recapture clinical remission of IBD.
PubMed: 38877332
DOI: 10.1007/s10620-024-08515-5 -
Journal of the American Academy of... Jun 2024
PubMed: 38876172
DOI: 10.1016/j.jaad.2024.06.008 -
Environmental Science and Pollution... Jun 2024
PubMed: 38866936
DOI: 10.1007/s11356-024-33995-3 -
Value in Health Regional Issues Jun 2024This study investigated the epidemiology, treatment patterns, and resource utilization in patients with alopecia areata (AA) in Taiwan using the National Health...
OBJECTIVES
This study investigated the epidemiology, treatment patterns, and resource utilization in patients with alopecia areata (AA) in Taiwan using the National Health Insurance Research Database. AA severity was determined by treatment use and diagnostic codes in the year after enrollment (including corticosteroids, systemic immunosuppressants, topical immunotherapy, and phototherapy).
METHODS
The cross-sectional analysis was conducted to estimate the incidence and prevalence of AA from 2016 to 2020. For the longitudinal analysis, 2 cohorts were identified: mild/moderate and severe. The cohorts were matched based on age, gender, and comorbidities. Patients were enrolled upon their first claim with an AA diagnosis during the index period of 2017-2018.
RESULTS
The number of patients with AA increased from 3221 in 2016 to 3855 in 2020. The longitudinal analysis identified 1808 mild/moderate patients and 452 severe patients. Mild/moderate patients used higher levels of topical corticosteroids (82.41%) than severe patients (73.45%). Conversely, severe patients used more topical nonsteroids (41.81%) and systemic therapies (51.77%) than mild/moderate patients (0.44% and 16.15%, respectively). Oral glucocorticoids use was higher in severe patients (47.57%) relative to mild/moderate patients (14.88%), whereas the use of injectable forms was similar. The most used systemic immunosuppressants were methotrexate, cyclosporin, and azathioprine. Topical immunotherapy utilization decreased with subsequent treatment lines for severe patients. Treatment persistence at 6 months was low for all treatments. Severe patients had higher annual AA-related outpatient visits than the mild/moderate cohort.
CONCLUSIONS
These findings highlight the need for additional innovations and therapies to address the clinical and economic burden of AA.
PubMed: 38865765
DOI: 10.1016/j.vhri.2024.101007 -
Hepatology (Baltimore, Md.) Jun 2024While avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to...
BACKGROUND AIMS
While avoidance of long-term corticosteroids is a common objective in the management of autoimmune hepatitis (AIH), prolonged immunosuppression is usually required to prevent disease progression. This study investigates the patient and provider factors associated with treatment patterns in U.S. patients with AIH.
APPROACH RESULTS
A retrospective cohort of adults with incident and prevalent AIH was identified from Optum's de-identified Clinformatics® Data Mart Database. All patients were followed for at least 2 years, with exposures assessed during the first year and treatment patterns during the second. Patient and provider factors associated with corticosteroid-sparing monotherapy and cumulative prednisone use were identified using multivariable logistic and linear regression, respectively.The cohort was 81.2% female, 66.3% White, 11.3% Black, 11.2% Hispanic and with median age 61 years. Among 2,203 patients with ≥1 AIH prescription fill, 83.1% received a single regimen for >6 months of the observation year, which included 52.2% azathioprine monotherapy, 16.9% azathioprine/prednisone and 13.3% prednisone monotherapy. Budesonide use was uncommon (2.1% combination, 1.9% monotherapy). Hispanic ethnicity (aOR 0.56; p=0.006), cirrhosis (aOR 0.73; p=0.019), osteoporosis (aOR 0.54; p=0.001) and top quintile of provider AIH experience (aOR 0.66; p=0.005) were independently associated with lower use of corticosteroid-sparing monotherapy. Cumulative prednisone use was greater with diabetes (+441 mg/year; p=0.004), osteoporosis (+749 mg/year; p<0.001) and highly experienced providers (+556 mg/year; p<0.001).
CONCLUSIONS
Long-term prednisone therapy remains common, and unexpectedly higher among patients with comorbidities potentially aggravated by corticosteroids. The greater use of corticosteroid-based therapy with highly experienced providers may reflect more treatment-refractory disease.
PubMed: 38865589
DOI: 10.1097/HEP.0000000000000961 -
The Cochrane Database of Systematic... Jun 2024IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis. It is a heterogeneous disease with different presentations and high morbidity. Thirty per... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis. It is a heterogeneous disease with different presentations and high morbidity. Thirty per cent of adults and 20% of children (followed into adulthood) will have a 50% decline in kidney function or develop kidney failure after 10 years.
OBJECTIVES
To determine the benefits and harms of immunosuppressive therapy for the treatment of IgAN in children.
SEARCH METHODS
We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 03 October 2023 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) investigating the treatment of IgAN in children with immunosuppressive therapies compared to placebo, no treatment, supportive care, standard therapy (Japanese protocol), other immunosuppressive therapies or non-immunosuppressive therapies.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed the risk of bias. Random effects meta-analyses were used to summarise estimates of treatment effects. Treatment effects were expressed as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes, and the mean difference (MD) and 95% CI for continuous outcomes. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs and the ROBIN-I tool for NRSIs. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE).
MAIN RESULTS
This review included 13 studies with 686 participants. Ten RCTs included 334 children and 191 adults, and three NRSIs included 151 participants, all children. Most participants had mild kidney disease. The risk of bias was unclear for most of the domains relating to allocation concealment, blinding of participants, personnel, and outcome assessment. In children with IgAN, it is uncertain if corticosteroid (steroid) therapy, compared to placebo reduces proteinuria (1 study, 64 children and young adults: RR 0.47, 95% CI 0.13 to 1.72; low certainty evidence) or the decline in estimated glomerular filtration rate (eGFR) (1 study, 64 children and young adults: RR 0.47, 95% CI 0.09 to 2.39; low certainty evidence). It is uncertain if steroids reduce proteinuria compared to supportive care (2 studies, 61 children: RR 0.04, 95% CI -0.83 to 0.72; low certainty evidence). Adverse events associated with steroid therapy were not assessed due to heterogeneity in steroid protocols, including dose and duration, and lack of systematic assessment for adverse events in the included studies. Azathioprine, mycophenolate mofetil, mizoribine, or cyclophosphamide alone or in combination with steroid therapy had uncertain effects on improving proteinuria or preventing eGFR decline in children with IgAN. Fish oil, vitamin E and tonsillectomy had uncertain effects on improving proteinuria or preventing eGFR decline. Effects of other immunosuppressive therapies, secondary outcomes and adverse events were not assessed due to insufficient data.
AUTHORS' CONCLUSIONS
There is a lack of high-quality evidence to guide the management of IgAN in children. There is no evidence to indicate that steroids, other immunosuppressive therapies, or tonsillectomy, when added to optimal supportive care, prevent a decline in eGFR or proteinuria in children with IgAN. Available studies were few, with small numbers, low-quality evidence, high or uncertain risk of bias, did not systematically assess harms associated with treatment, or report net benefits or harms. Severe cases and atypical presentations of IgAN were not included in the reviewed studies, and our findings cannot be generalised to these situations.
Topics: Adolescent; Child; Humans; Bias; Disease Progression; Glomerular Filtration Rate; Glomerulonephritis, IGA; Immunosuppressive Agents; Mycophenolic Acid; Placebos; Proteinuria; Randomized Controlled Trials as Topic; Young Adult
PubMed: 38864363
DOI: 10.1002/14651858.CD015060.pub2 -
Alimentary Pharmacology & Therapeutics Jul 2024Rapidity of effect of advanced therapies for patients with Crohn's disease (CD) can be an essential decision parameter; however, comparative evaluation is lacking. We... (Meta-Analysis)
Meta-Analysis Comparative Study Review
INTRODUCTION
Rapidity of effect of advanced therapies for patients with Crohn's disease (CD) can be an essential decision parameter; however, comparative evaluation is lacking. We aimed to compare early response for advanced CD therapies in a network meta-analysis (NMA).
METHODS
We searched systematically MEDLINE, Embase, and CENTRAL up to 19 February 2024, for randomised controlled trials. The co-primary outcomes were induction of clinical remission (Crohn's Disease Activity Index (CDAI) ≤150) and clinical response (≥100-point reduction in CDAI) within the first 6 weeks of treatment. We incorporated any assessment within this time point in a Bayesian random-effects NMA following PRISMA-NMA guidance (PROSPERO ID: CRD42022368509).
RESULTS
Twenty-five studies, comprising 7414 patients, were included. Infliximab combined with azathioprine or monotherapy ranked highest for induction of clinical remission within 6 weeks and was significantly superior to certolizumab, ustekinumab, guselkumab, vedolizumab, and upadacitinib. However, superiority over risankizumab 600 mg and adalimumab 160/80 mg was non-significant. Accordingly, infliximab in combination with azathioprine and guselkumab 600 mg ranked highest in the corresponding analysis of clinical response with no statistical significance demonstrated. Among bio-exposed patients, none of whom received infliximab, upadacitinib, and risankizumab induced the highest clinical responses. On the other hand, vedolizumab, certolizumab, and ustekinumab ranked lowest across the analyses.
CONCLUSIONS
We found infliximab to be ranked highest and superior to all other agents but risankizumab and adalimumab, demonstrating the highest probability of early induction of remission. Upadacitinib and risankizumab induced the highest clinical responses in bio-exposed patients. However, infliximab was not investigated in this population.
Topics: Humans; Crohn Disease; Network Meta-Analysis; Biological Products; Treatment Outcome; Randomized Controlled Trials as Topic; Drug Therapy, Combination; Infliximab; Gastrointestinal Agents; Remission Induction; Severity of Illness Index
PubMed: 38863153
DOI: 10.1111/apt.18110 -
Cureus May 2024Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune disorder characterized by recurrent episodes of demyelination affecting the...
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare autoimmune disorder characterized by recurrent episodes of demyelination affecting the central nervous system. The following case report showcases a thorough analysis of a 21-year-old female patient presenting with MOGAD, outlining her clinical presentation, diagnostic workup, treatment protocol, and long-term management outcomes. Through a multidisciplinary approach, we aim to augment the understanding of this complex neurological entity and steer optimal therapeutic interventions.
PubMed: 38854354
DOI: 10.7759/cureus.59840