scholarly journals Demyelinating Disease following Anti-TNFa Treatment: A Causal or Coincidental Association? Report of Four Cases and Review of the Literature

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
E. Andreadou ◽  
E. Kemanetzoglou ◽  
Ch. Brokalaki ◽  
M. E. Evangelopoulos ◽  
C. Kilidireas ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Adverse Events ◽  
Demyelinating Disease ◽  
Therapeutic Option ◽  
Brain Mri ◽  
Clinical Manifestations ◽  
Clinical Effectiveness ◽  
Oligoclonal Bands ◽  
Cns Demyelination

Tumor necrosis factor antagonists (anti-TNFa) are an established therapeutic option for several autoimmune and inflammatory bowel diseases. Despite their clinical effectiveness, neurological adverse events have been reported and literature data suggest a potential role of anti-TNFa in the induction of demyelination of the CNS. We present four patients treated with anti-TNFa who developed symptoms suggestive of CNS demyelination. The first patient, a 17-year-old male who received etanercept for psoriatic arthritis for eight months, presented with dysesthesias up to T4 level. The second patient, a 30-year-old male treated with adalimumab for three years due to ankylosing spondylitis, presented with right unilateral tinnitus. The third case, a 47-year-old female, received etanercept for four years because of psoriatic arthritis and developed persistent headache and left-sided face and head numbness. Finally, the fourth patient, a 57-years-old female treated with etanercept for six years due to ankylosing spondylitis, presented with difficulty in speech, swallowing, and ptosis of the right corner of the mouth. In all cases, brain MRI showed lesions suggestive of demyelination, while positive oligoclonal bands were detected in the CSF. Anti-TNFa treatments were discontinued and patients showed clinical improvement with pulsed intravenous corticosteroid therapy. CNS demyelination following anti-TNFa treatment represents a relatively rare but potential serious complication. Close follow-up and MRI monitoring of these patients is mandatory to elucidate whether the clinical manifestations represent adverse events occurring during anti-TNFa therapy or a first demyelinating episode.

scholarly journals AB0649 REAL WORLD EFFICACY OF SECUKINUMAB: A SINGLE CENTRE EXPERIENCE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1619-1620
Author(s):  
G. Kasavkar ◽  
T. Blake ◽  
N. Gullick
Keyword(s):  
Clinical Trial ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Adverse Events ◽  
Real World ◽  
Certolizumab Pegol ◽  
Tender Joint Count ◽  
Inadequate Response ◽  
Technology Appraisal ◽  
New Onset

Background:Secukinumab was approved by NICE for patients with active Ankylosing Spondylitis and Psoriatic Arthritis in 2017. Clinical trial data suggests secukinumab is a useful treatment option in both conditions, but often real world experience differs greatly from clinical trial results. In addition, patients with more refractory disease are often excluded from clinical trials.Objectives:To assess the response to secukinumab in patients with seronegative spondyloarthropathy receiving treatment at University Hospital Coventry and WarwickshireMethods:Patients starting secukinumab at UHCW were identified from the Blueteq funding database. Medical notes were reviewed retrospectively to assess response rates using BASDAI responses in Ankylosing spondylitis and PsARC responses in PsA. Patients who had previously had inadequate response to TNF inhibitors (PsA only) and severe psoriasis received 300mg secukinumab monthly; the remainder were prescribed 150mg monthly.Results:146 patients commenced secukinumab between June 2017 and January 2020 and had outcome data recorded. 73 patients (50%) had received previous biologic agents prior to secukinumab exposure. Patients with Ankylosing spondylitis had high BASDAI (6.8±1.4) and spinal pain (7.5±1.4). 48 patients had an initial response to treatment as per outcome measures done before and after Secukinumab inception. Secukinumab was effective in 89 patients (94%), and 87 (91%) continued treatment.In psoriatic arthritis, despite high levels of activity at baseline (mean tender joint count 10±8; swollen joint count 6±3) and 65% prior biologic exposure; high rates of response were seen. The majority of patients have continued treatment. Secukinumab was well tolerated in both patient groups with low rates of discontinuation due to adverse events (8 patients, 5%). Adverse events included recurrent infection (3), rash (1), mouth ulcers (1), vertigo (1), new onset cancer (1) and new onset Crohn’s (1) although rates were low overall. Patients with pre-existing uveitis did not develop exacerbations but low numbers of patients with prior uveitis were treated.PsA (n=51)AS (n=95)Age in years, mean (SD)53 (13)49(12)Male sex, n (%)21 (41)62 (65)Disease duration in years, mean (SD)8 (8)10.9 (9.2)Previous biologic exposure, n (%)30 (65)43 (48)Number of prior biologics, median (range)1 (1-4)1 (1-4)Responder, n (%)37 (72)*89 (93)Discontinuation, n(%)12 (24)8 (8.5)Adverse events62Lack of efficacy64Other02*Response could not be assessed in 3/51 PsA patients due to insufficient clinical data; these patients have been recorded as non respondersConclusion:Secukinumab demonstrates high levels of efficacy even in a cohort of patients with longstanding PSA and AS with high rates of inadequate responses to other biologics.Secukinumab is well tolerated with low rates of discontinuation due to adverse events.References:Certolizumab pegol and secukinumab for treating active psoriatic arthritis after inadequate response to DMARDs Technology appraisal guidance [TA445]Secukinumab for active ankylosing spondylitis after treatment with non-steroidal anti-inflammatory drugs or TNF-alpha inhibitors Technology appraisal guidance [TA407]Disclosure of Interests:None declared

scholarly journals EFFICACY AND SAFETY OF ADALIMUMAB IN ANKYLOSING SPONDYLITIS: DATA FROM REAL LIFE

2015 ◽  
Vol 24 (1) ◽  
pp. 44-49
Author(s):  
Claudiu Popescu ◽  
◽  
Cristina Coroama ◽  
Costin Mitulescu ◽  
Denisa Predeteanu ◽  
...  
Keyword(s):  
Ankylosing Spondylitis ◽  
Adverse Events ◽  
Clinical Setting ◽  
Demyelinating Disease ◽  
Real Life ◽  
Time Frame ◽  
University Hospital ◽  
Controlled Trials ◽  
Efficacy And Safety ◽  
Serious Adverse Events

Rationale. Data from controlled trials showed that adalimumab, a humanized anti-TNF monoclonal antibody, is effective and safe in the treatment of ankylosing spondylitis (AS). Objectives. The present study aimed to observe the effi cacy and safety of adalimumab in AS in a real life clinical setting. Methods. The study observed cross-sectionaly and retrospectively the efficacy and safety of adalimumab in all the patients admitted to the Rheumatology Department of “Sfânta Maria” Clinical Hospital between January 2008 and June 2013 who were classified as having AS according to the modified New York criteria. The diagnosis and follow-up of uveitic cases were done in the Ophthalmology Department of the Emergency University Hospital. Results. Within the study time-frame, 79 AS patients met the inclusion criteria: 71 (89.9%) had adalimumab for at least 24 months; 8 (10.1%) switched from adalimumab to another biological, as follows: 3 (3.8%) because of serious adverse events, 3 (3.8%) were primary non-responders and 2 (2.5%) were secondary non-responders. The clinical response was fast: after 3 months of treatment, 59 (83.1%) patients had BASDAI < 4 and 55 (77.5%) patients had BASFI < 4. Regarding safety, the serious adverse effects recorded were: infectious arthritis, pulmonary tuberculosis, pulmonary sarcoidosis. There were no cases of cancer or demyelinating disease during the study frame. Conclusions. Therapy with adalimumab in AS produces a prompt and lasting effect. The efficacy (remission) and safety (adverse events) of adalimumab can be monitored in the real-life clinical setting using BASDAI, BASFI, and routine clinical evaluations. Clinicians may need to expect a slightly higher rate of serious adverse events and rate of treatment discontinuation than those reported by controlled trials.

scholarly journals P191 Secukinumab demonstrates a consistent safety profile in patients with psoriasis, psoriatic arthritis and ankylosing spondylitis over long term: updated pooled safety analyses

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Iain B McInnes ◽  
Xenofon Baraliakos ◽  
Atul Deodhar ◽  
Alice B Gottlieb ◽  
Mark Lebwohl ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Adverse Events ◽  
Safety Data ◽  
Cardiac Events ◽  
Research Support ◽  
Phase 3 ◽  
Research Grants ◽  
Adverse Cardiac Events ◽  
Post Marketing

Abstract Background/Aims  Pooled safety data have been reported with secukinumab in patients with psoriatic arthritis (PsA), ankylosing spondylitis (AS) and psoriasis (PsO). Here we report longterm safety data for secukinumab in patients with PsA, AS or PsO up to 5 years. Methods  The integrated clinical trial safety dataset included data pooled from 28 randomised controlled clinical trials of secukinumab 300, 150 or 75 mg in PsO (11 Phase 3 and 8 Phase 4 trials), PsA (5 Phase 3 trials) and AS (4 Phase 3 trials), along with post-marketing safety surveillance data starting 26 December 2014, with a cut-off date of 25 December 2018. Adverse events were reported as exposure-adjusted incident rates (EAIRs) per 100 patient-years. Analyses included all patients who received ≥1 dose of secukinumab. Results  A total of 12,637 patients (8,819, 2,678 and 1,140 patients with PsO, PsA and AS, with an exposure of 15,063.1, 5,984.6 and 3,527.2 patient-years, respectively) were included. The most frequent adverse event was upper respiratory tract infection and the EAIR per 100 patient-years for inflammatory bowel disease (IBD), malignancies and major adverse cardiac events (MACE) remained low. The EAIR per 100 patient-years for adverse events of special interest are reported in Table 1. The cumulative post-marketing exposure to secukinumab was estimated to be ∼285,811 patient-years across the approved indications. Post-marketing safety data showed cumulative reporting rates of 1.4, 0.3, 0.2 and 0.2 patienttreatment years for serious infections, malignancy, total IBD and MACE, respectively. Conclusion  Secukinumab was well tolerated in this long-term analysis of patients with PsO, PsA and AS across clinical trials and post-marketing surveillance, with a safety profile consistent with previous reports (Deodhar, 2019). P191 Table 1:Selected adverse events of interest with secukinumab across pooled clinical trialsVariablePsOPsAASSEC N = 8,819SEC N = 2,678SEC N = 1,140Exposure (days),mean (SD)623.9 (567.7)816.2 (580.7)1130.1 (583.0)Death, n (%)14 (0.2)11 (0.4)9 (0.8)Selected adverse events of interest, EAIR (95% CI)Serious infectionsa1.4 (1.2-1.6)1.8 (1.5-2.2)1.2 (0.9-1.6)Candida infectionsb2.9 (2.7-3.2)1.5 (1.2-1.9)0.7 (0.5-1.1)IBDc0.01 (0.0-0.05)0.03 (0.0-0.1)0.03 (0.0-0.2)Crohns diseasec0.1 (0.05-0.2)0.1 (0.04-0.2)0.4 (0.24-0.7)Ulcerative colitisc0.1 (0.08-0.2)0.1 (0.04-0.2)0.2 (0.1-0.5)MACEd0.4 (0.3-0.5)0.4 (0.3-0.6)0.7 (0.4-1.0)Uveitisc0.01 (0.0-0.05)0.1 (0.04-0.2)1.2 (0.9-1.7)Malignancye0.9 (0.7-1.0)1.0 (0.77-1.3)0.5 (0.3-0.8)aRates for system organ class;bRates for high level term;cRates for preferred term (PT; IBD for unspecified IBD);dRates for Novartis MedDRA Query term;eRates for standardised MedDRA Query term - ‘malignancies and unspecified tumour’. AS, ankylosing spondylitis; CI, confidence interval; EAIR, exposure-adjusted incidence rate per 100 patient-years; IBD, inflammatory bowel disease; MACE, major adverse cardiac events; MedDRA, Medical Dictionary for Regulatory Activities; N, number of patients in the analysis; PsA, psoriatic arthritis; PsO, psoriasis; PT, preferred term; SD, standard deviation; SEC, secukinumab. Disclosure  I. McInnes: Other; I.M. has received research grants, consultation fees or speaker honoraria from AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Novartis, Pfizer and UCB. X. Baraliakos: Consultancies; X.B. is a consultant for AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen. Member of speakers’ bureau; X.B. is a member of the speakers' bureau for AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen. Grants/research support; X.B. has received grant/research support from AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen. A. Deodhar: Other; A.D. has received honoraria for consulting or speaking for, or has received research grants from AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb (BMS), Eli Lilly, GlaxoSmithKline (GSK), Janssen, Novartis, Pfizer and UCB. A. Gottlieb: Other; A.G. has received research grants, consultation fees or speaker honoraria for lectures from Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB. M. Lebwohl: Consultancies; M.L. is a consultant for Allergan, Almirall, Arcutis, Inc., Avotres Therapeutics, BirchBioMed Inc., Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Foundation for Research and Education in Dermatology, Inozyme Pharma, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Theravance and Verrica. Grants/research support; M.B. receives receives research funds from AbbVie, Amgen, Arcutis, AstraZeneca, Boehringer Ingelheim, Celgene, Clinuvel, Eli Lilly, Incyte, Janssen Research & Development, LLC, Kadmon Corp., LLC, LEO Pharma, Medimmune, Novartis, Ortho Dermatologics, Pfizer, Sciderm, UCB, Inc. and ViDac. S. Schreiber: Consultancies; S.S. has received consultation fees from AbbVie, Arena, BMS, Biogen, Celltrion, Celgene, IMAB, Gilead, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, Provention Bio, Protagonist, and Dr Falk Pharma. K. Marfo: Other; K.M. is an employee of Novartis with Novartis stock. W. Bao: Other; W.B. is an employee of Novartis with Novartis stock. H. Richards: Other; H.B.R. is an employee of Novartis with Novartis stock. L. Pricop: Other; L.P. is an employee of Novartis with Novartis stock. A. Shete: Other; A.S. is an employee of Novartis with Novartis stock. J. Safi: Other; J.S. is an employee of Novartis with Novartis stock. P. Mease: Consultancies; P.M. is a consultant for AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB. Member of speakers’ bureau; P.M. is a member of the speakers' bureau for AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB. Grants/research support; P.M. has received grant/research support from AbbVie, Amgen, BMS, Celgene, Crescendo Bioscience, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB.

scholarly journals Case Report: Anti-NMDAR Encephalitis With Anti-MOG CNS Demyelination After Recurrent CNS Demyelination

2021 ◽  
Vol 12 ◽  
Author(s):  
Bing-Yan Ren ◽  
Yi Guo ◽  
Jing Han ◽  
Qian Wang ◽  
Zai-Wang Li
Keyword(s):  
Case Report ◽  
Brain Mri ◽  
Clinical Manifestations ◽  
Epileptic Seizures ◽  
Autoimmune Disorder ◽  
Pulse Therapy ◽  
Nmdar Encephalitis ◽  
Cns Demyelination ◽  
Magnetic Resonance Imaging Mri ◽  
The Right

Introduction: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, a serious neurological autoimmune disorder caused by autoantibodies with diverse clinical manifestations, may simultaneously onset with antimyelin oligodendrocyte glycoprotein (MOG) demyelination after recurrent central nervous system (CNS) demyelination.Case Report: We present a case of anti-NMDAR encephalitis combining with anti-MOG CNS demyelination following recurrent CNS demyelination. A 38-year-old man admitted to hospital developed epileptic seizures following recurrent episodes of cross-sensory disturbance and dizziness. Magnetic resonance imaging (MRI) showed a demyelinating lesion in the right brainstem initially. Despite a good response to methylprednisolone pulse therapy at the beginning, the patient still had relapses and progression after corticosteroid reduction or withdrawal. Then brain MRI discovered new serpentine lesions involving extensive cerebral cortex on his second relapse. Repeat autoantibodies test indicated cerebrospinal fluid (CSF) NMDAR antibodies coexisted with MOG-Abs simultaneously, suggesting the diagnosis of anti-NMDAR encephalitis with anti-MOG CNS demyelination.Results: After a definite diagnosis, the patient was treated with mycophenolate mofetil (MMF) and corticosteroid. He was discharged after his symptoms ameliorated. No neurological sequels remained, and there were no effects on his activities of daily living after 6 months of immunoregulatory therapy of MMF and corticosteroid.Conclusion: For individuals with recurrent CNS demyelination, especially combining with cortical encephalitis, repeated detection of autoantibodies against AE, and demyelination in CSF/serum can be helpful to enable a definite early diagnosis. For patients who suffer from anti-NMDAR encephalitis combining with anti-MOG CNS demyelination, second-line immunotherapy is recommended when first-line treatment such as steroids, intravenous immunoglobulin G (IVIG) and plasma exchange has been proven ineffective to prevent the relapse of disease.

EFFICACY AND SAFETY OF TOFACITINIB IN PATIENTS WITH PSORIATIC ARTHRITIS IN REAL CLINICAL PRACTICE

2020 ◽  
Vol 58 (3) ◽  
pp. 268-275
Author(s):  
E. Yu. Loginova ◽  
Yu. L. Korsakova ◽  
E. E. Gubar ◽  
P. L. Karpova ◽  
T. V. Korotaeva
Keyword(s):  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Clinical Manifestations ◽  
Activity Score ◽  
Tender Joint Count ◽  
Efficacy And Safety ◽  
Low Disease Activity ◽  
Number Of Patients

Objective: to evaluate the clinical efficacy and safety of the targeted synthetic disease-modifying anti-rheumatic drug (DMARD) tofacitinib (TOFA; Yakvinus®) in patients with active psoriatic arthritis (PsA) at 12 and 24 weeks after starting treatment. To define the place of TOFA in the therapy of PsA patients. Subjects and methods. Examinations were made in 41 patients (17 men and 24 women) with active PsA and an insufficient response to previous treatment with synthetic DMARDs and/or biological agents (BA). Before starting therapy, the median disease activity for psoriatic arthritis (DAPSA) and disease activity score (DAS28) were 44.2 [37.8; 55.3] and 5.5 [4.7; 6.1], respectively. TOFA tablets were prescribed at a dose of 5 mg twice daily for 24 weeks with possible dose escalation to 10 mg twice daily after 12 weeks. At the beginning of the investigation, at 12 and 24 weeks, the investigators assessed disease activity and TOFA therapy efficiency of according to DAPSA, DAS28 and minimal disease activity (MDA) criteria: tender joint count ≤1, swollen joint count ≤1, a psoriasis area severity index (PASI) ≤1 or body surface area (BSA) ≤3%, pain intensity ≤15 mm, patient global assessment ≤20 mm, Health Assessment Questionnaire (HAQ) ≤0.5, and enthesitis ≤1. They also determined the number of patients who had achieved remission (DAPSA ≤4, DAS28 score <2.6), low disease activity (DAPSA 5-14, ≤2.6, DAS28 <3.2) or MDA (5 out of the 7 criteria) during TOFA therapy at 24-week follow-up. The safety of therapy was evaluated by analyzing the drug-induced adverse events (AE): the frequency, severity and time of their occurrence were studied. Results and discussion. At 24 weeks after initiation of TOFA therapy, there was a significant decrease of median DAPSA and DAS28 values as compared to baseline, to 11 [4.3; 17.3] and 2.6 [1.7; 3.4] respectively. The median Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) also significantly decreased from 6 [4.2; 7] and 3.8 [2.8; 4.4] to 1.4 [0.6; 3.2] and 1.5 [1; 2.1] respectively. The median BSA was significantly reduced from 3 [1; 5] to 0.5 [0.1; 2]. At 24 weeks after initiation of TOFA therapy, DAPSA and DAS28 low disease activity/remission were achieved by 38.5/23.1% and 17.9/53.9% of patients, respectively. Fifteen (38.5%) patients achieved MDA. 38 (92.7%) of the 41 patients completed a full TOFA therapy cycle. Two patients dropped out of the investigation due to ineffective therapy and one due to AE (diarrhea occurring up to 10 times daily, headache, elevated blood pressure, and lacrimation). At 24 weeks, 14 (34.2%) patients reported to have AE. The most common AE noted in 7 (17.1%) patients were infections: acute respiratory viral infection (n=3), fever (n=2), and folliculitis (n=2). In addition, two patients had diarrhea and two had headache. Conclusion. TOFA is an effective drug for the treatment of PsA patients with moderate or high inflammatory activity, has a significant effect on all clinical manifestations of PsA and has a satisfactory safety profile.

scholarly journals Radiologically isolated syndrome in children

2017 ◽  
Vol 4 (6) ◽  
pp. e395 ◽  
Author(s):  
Naila Makhani ◽  
Christine Lebrun ◽  
Aksel Siva ◽  
David Brassat ◽  
Clarisse Carra Dallière ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Demyelinating Disease ◽  
Clinical Symptoms ◽  
Clinical Event ◽  
Oligoclonal Bands ◽  
Spinal Cord Lesions ◽  
Historical Cohort ◽  
Radiologically Isolated Syndrome ◽  
Increased Risk ◽  
Cns Demyelination

Objective:To describe clinical and radiologic outcomes of children with incidental findings on neuroimaging suggestive of CNS demyelination (termed “radiologically isolated syndrome” or RIS).Methods:Clinical and radiologic data were obtained from a historical cohort of children with no symptoms of demyelinating disease who had MRI scans that met the 2010 MRI criteria for dissemination in space for MS.Results:We identified 38 children (27 girls and 11 boys) with RIS now being prospectively followed at 16 sites in 6 countries. The mean follow-up time was 4.8 ± 5.3 years. The most common reason for initial neuroimaging was headache (20/38, 53%). A first clinical event consistent with CNS demyelination occurred in 16/38 children (42%; 95% confidence interval [CI]: 27%–60%) in a median of 2.0 years (interquartile range [IQR] 1.0–4.3 years). Radiologic evolution developed in 23/38 children (61%; 95% CI: 44%–76%) in a median of 1.1 years (IQR 0.5–1.9 years). The presence of ≥2 unique oligoclonal bands in CSF (hazard ratio [HR] 10.9, 95% CI: 1.4–86.2, p = 0.02) and spinal cord lesions on MRI (HR 7.8, 95% CI: 1.4–43.6, p = 0.02) were associated with an increased risk of a first clinical event after adjustment for age and sex.Conclusions:We describe the clinical characteristics and outcomes of children with incidental MRI findings highly suggestive of CNS demyelination. Children with RIS had a substantial risk of subsequent clinical symptoms and/or radiologic evolution. The presence of oligoclonal bands in CSF and spinal cord lesions on MRI were associated with an increased risk of a first clinical event.

scholarly journals Understanding the Pathogenesis of Spondyloarthritis

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1461
Author(s):  
Aigul Sharip ◽  
Jeannette Kunz
Keyword(s):  
Inflammatory Bowel Disease ◽  
Endoplasmic Reticulum ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Inflammatory Diseases ◽  
Clinical Manifestations ◽  
Unfolded Protein ◽  
Exact Etiology ◽  
Inflammatory Bowel ◽  
Protein Response

Spondyloarthritis comprises a group of inflammatory diseases of the joints and spine, with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B*27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B*27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B*27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.

scholarly journals Myelin Oligodendrocyte Glycoprotein Antibody Associated Cerebral Cortical Encephalitis: Case Reports and Review of Literature

2022 ◽  
Vol 15 ◽  
Author(s):  
Hang Shu ◽  
Manqiu Ding ◽  
Pei Shang ◽  
Jia Song ◽  
Yue Lang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Demyelinating Disease ◽  
Age Of Onset ◽  
Clinical Phenotype ◽  
Brain Mri ◽  
Clinical Manifestations ◽  
Myelin Oligodendrocyte Glycoprotein ◽  
Lessons Learned ◽  
Population Characteristics ◽  
High Dose

Myelin oligodendrocyte glycoprotein antibody-associated disease is an immune-mediated demyelinating disease of the central nervous system that is present in both adults and children. The most common clinical manifestations are optic neuritis, myelitis, acute disseminated encephalomyelitis, and brainstem syndrome. Cerebral cortical encephalitis (CCE) is a rare clinical phenotype of myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), which usually begins with seizures, headaches, and fever, and may be misdiagnosed as viral encephalitis in the early stages. Herein, we report two typical MOG antibody (MOG-Ab)-positive patients presenting with CCE, both of whom presented with headache, fever, seizures, and who recovered completely after immunotherapy. In addition, we performed a systematic review of the present literature from the perspectives of population characteristics, clinical symptoms, MRI abnormalities, treatments, and prognosis. Among the patients reported in 25 articles, 33 met our inclusion criteria, with the age of onset ranging from 4 to 52 years. Most of the patients had seizures, headache, fever, and unilateral cortical lesions on brain MRI. For acute CCE, 30 patients were treated with high-dose intravenous methylprednisolone, and the symptoms of most patients were completely relieved after immunotherapy. This study reported our experience and lessons learned in the diagnosis and treatment of MOG-Ab-positive CCE and provides a systematic review of the literature to analyse this rare clinical phenotype.

scholarly journals Undifferentiated seronegative spondyloarthritis with inflammatory bowel disease and a family history of psoriasis. Sicca syndrome

2013 ◽  
pp. 189-191
Author(s):  
Norma Marigliano ◽  
Domenico Galasso
Keyword(s):  
Inflammatory Bowel Disease ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Bowel Disease ◽  
Acute Inflammation ◽  
Clinical Manifestations ◽  
Hla B27 ◽  
History Of ◽  
Seronegative Spondyloarthritis ◽  
Inflammatory Bowel

Background: Seronegative spondyloarthritis is characterized by the presence of subcutaneous nodules, asymmetrical peripheral arthritis, sacroileitis with or without spondylitis, and rheumatoid-factor negativity. Other common clinical manifestations include oral ulcers, conjunctivitis, and cutaneous lesions such as psoriasis. Familial aggregation has also been described. According to the 1986 classification, corresponding clinical entities include ankylosing spondylitis, psoriatic arthritis, Reiter’s syndrome, arthritis associated with inflammatory bowel disease (IBD), and undifferentiated spondyloarthritis. The disease is also frequently associated with the HLA B27 antigen. From the clinical point of view, there are often incomplete forms of spondyloarthritis, such as reactive arthritis triggered by asymptomatic infections, psoriatic arthritis without psoriasis itself, initial phases of specific forms of spondyloarthritis or the phase of ankylosing spondylitis characterized by sacroiliac lesions, and all forms that remain undifferentiated for long periods of time. Moreover, there are close relations between arthropathy and IBDs, such as Crohn’s disease, ulcerative colitis, and Whipple’s syndrome. Recently, microscopic inflammatory bowel lesions and psoriatic arthritis have been described. Case report: A 30-year-old man (HLA B27-negative) who had been vaccinated against TBC and HBV presented with a 6-year history of recurrent episodes of predominantly left-sided sciatica. The pain was worse at night and during rest. He was suffering from bilateral sacroileitis without spondylitis. Three to five times a day, usually after eating, he passed watery feces containing mucous and small amounts of bright red blood. Colonoscopy revealed pancolitis with histological evidence of chronic inflammation interspersed with areas of acute inflammation, edema, hyperemia, and glandular distortion. One year later, the clinical manifestations and histological findings were essentially unchanged: glandular distortions, chronic and acute inflammation of the lamina propria and crypt microabscesses. There were no granulomas and no evidence of uveitis. The inflammatory index was positive; FR, ENA, ANA titers were negative. He began therapy with adalimumab (loading dose 80 mg followed by 40 mg every 15 days) and mesalazine (2.4 g per os), and the clinical manifestations of the disease improved significantly.

Secukinumab Immunogenicity over 52 Weeks in Patients with Psoriatic Arthritis and Ankylosing Spondylitis

2019 ◽  
Vol 47 (4) ◽  
pp. 539-547 ◽  
Author(s):  
Atul Deodhar ◽  
Dafna D. Gladman ◽  
Iain B. McInnes ◽  
Sebastian Spindeldreher ◽  
Ruvie Martin ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Psoriatic Arthritis ◽  
Ankylosing Spondylitis ◽  
Adverse Events ◽  
Dose Frequency ◽  
Link Type ◽  
Antidrug Antibodies ◽  
Neutralizing Potential

Objective.Secukinumab, a fully human antiinterleukin 17A monoclonal antibody, is efficacious for the treatment of psoriatic arthritis (PsA) and ankylosing spondylitis (AS). This study examined the immunogenicity of secukinumab in patients with PsA and AS exposed to secukinumab for up to 52 weeks.Methods.Antibody bridging assays were used to assess the immunogenicity of secukinumab in patients with PsA [FUTURE 1–3 studies, and AS (MEASURE 1–4 studies)]. Evaluations were at baseline and at weeks 16 (AS only), 24, and 52. Treatment-emergent antidrug antibodies (TE-ADA) were defined as a positive ADA signal in ≥ 1 posttreatment sample in patients negative at baseline. Positive samples were analyzed for drug-neutralizing potential, and effect of TE-ADA on secukinumab pharmacokinetics, immunogenicity-related adverse events (AE), and efficacy through Week 52 were assessed.Results.Of 1414 treated PsA and 1164 treated AS patients with samples available for immunogenicity evaluation, 5 (0.35%) and 8 (0.69%), respectively, developed TE-ADA. All but 1 PsA patient were biologic-naive; two of the 5 PsA and one of the 8 AS patients received concomitant methotrexate, and two of the 8 AS patients received concomitant sulfasalazine. Associations between TE-ADA and secukinumab dose, frequency, or administration mode were not observed. Other than one PsA patient, all TE-ADA were non-neutralizing. No TE-ADA were associated with any AE. All TE-ADA were associated with normal secukinumab pharmacokinetics and none were associated with loss of secukinumab efficacy.Conclusion.Secukinumab treatment was associated with a low (< 1%) incidence of immunogenicity in patients with PsA or AS. (clinicaltrials.gov: NCT01392326; NCT01752634; NCT01989468; NCT01358175; NCT01649375; NCT02008916; NCT02159053)

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