Presentation1_Disproportional signal of pericarditis with biological diseasemodifying antirheumatic drugs (bDMARDs) in patients with ankylosing spondylitis: a disproportionality analysis in the FAERS database.PPTX

Objective: This study aimed to investigate the potential association between biological disease-modifying antirheumatic drugs (bDMARDs) and pericarditis and uncover relevant clinical characteristics in ankylosing spondylitis (AS).Methods: Reports of pericarditis recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004–December 2022) were identified through the preferred term “pericarditis.” Demographic and clinical characteristics were described, and disproportionality signals were assessed through the reporting odds ratio (ROR) and information component (IC). A significant signal was detected if the lower bound of IC (IC025) was more than zero.Results: We found 1,874 reports of pericarditis with bDMARDs (11.3% of cases with fatal outcomes). Adalimumab (IC025 3.24), infliximab (IC025 4.90), golimumab (IC025 5.40), certolizumab (IC025 5.43), etanercept (IC025 3.24), secukinumab (IC025 3.97), and ustekinumab (IC025 7.61) exhibit significant disproportionality signals compared to other medications in the FAERS database. After excluding pre-existing diseases and co-treated drugs that may increase the susceptibility of pericarditis, the disproportionality signal associated with infliximab, certolizumab, etanercept, secukinumab, and ustekinumab remained strong. Pericarditis cases associated with all bDMARDs were predominantly recorded in women aged 25–65 years.Conclusion: More reports of pericarditis were detected with AS patients on bDMARDs than with other drugs in the overall database. Further studies are warranted to investigate the underlying mechanisms and identify patient-related susceptibility factors, thus supporting timely diagnosis and safe(r) prescribing of bDMARDs.</p

Table2_Disproportional signal of pericarditis with biological diseasemodifying antirheumatic drugs (bDMARDs) in patients with ankylosing spondylitis: a disproportionality analysis in the FAERS database.XLSX

Objective: This study aimed to investigate the potential association between biological disease-modifying antirheumatic drugs (bDMARDs) and pericarditis and uncover relevant clinical characteristics in ankylosing spondylitis (AS).Methods: Reports of pericarditis recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004–December 2022) were identified through the preferred term “pericarditis.” Demographic and clinical characteristics were described, and disproportionality signals were assessed through the reporting odds ratio (ROR) and information component (IC). A significant signal was detected if the lower bound of IC (IC025) was more than zero.Results: We found 1,874 reports of pericarditis with bDMARDs (11.3% of cases with fatal outcomes). Adalimumab (IC025 3.24), infliximab (IC025 4.90), golimumab (IC025 5.40), certolizumab (IC025 5.43), etanercept (IC025 3.24), secukinumab (IC025 3.97), and ustekinumab (IC025 7.61) exhibit significant disproportionality signals compared to other medications in the FAERS database. After excluding pre-existing diseases and co-treated drugs that may increase the susceptibility of pericarditis, the disproportionality signal associated with infliximab, certolizumab, etanercept, secukinumab, and ustekinumab remained strong. Pericarditis cases associated with all bDMARDs were predominantly recorded in women aged 25–65 years.Conclusion: More reports of pericarditis were detected with AS patients on bDMARDs than with other drugs in the overall database. Further studies are warranted to investigate the underlying mechanisms and identify patient-related susceptibility factors, thus supporting timely diagnosis and safe(r) prescribing of bDMARDs.</p

Table3_Disproportional signal of pericarditis with biological diseasemodifying antirheumatic drugs (bDMARDs) in patients with ankylosing spondylitis: a disproportionality analysis in the FAERS database.XLSX

Objective: This study aimed to investigate the potential association between biological disease-modifying antirheumatic drugs (bDMARDs) and pericarditis and uncover relevant clinical characteristics in ankylosing spondylitis (AS).Methods: Reports of pericarditis recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004–December 2022) were identified through the preferred term “pericarditis.” Demographic and clinical characteristics were described, and disproportionality signals were assessed through the reporting odds ratio (ROR) and information component (IC). A significant signal was detected if the lower bound of IC (IC025) was more than zero.Results: We found 1,874 reports of pericarditis with bDMARDs (11.3% of cases with fatal outcomes). Adalimumab (IC025 3.24), infliximab (IC025 4.90), golimumab (IC025 5.40), certolizumab (IC025 5.43), etanercept (IC025 3.24), secukinumab (IC025 3.97), and ustekinumab (IC025 7.61) exhibit significant disproportionality signals compared to other medications in the FAERS database. After excluding pre-existing diseases and co-treated drugs that may increase the susceptibility of pericarditis, the disproportionality signal associated with infliximab, certolizumab, etanercept, secukinumab, and ustekinumab remained strong. Pericarditis cases associated with all bDMARDs were predominantly recorded in women aged 25–65 years.Conclusion: More reports of pericarditis were detected with AS patients on bDMARDs than with other drugs in the overall database. Further studies are warranted to investigate the underlying mechanisms and identify patient-related susceptibility factors, thus supporting timely diagnosis and safe(r) prescribing of bDMARDs.</p

Table1_Disproportional signal of pericarditis with biological diseasemodifying antirheumatic drugs (bDMARDs) in patients with ankylosing spondylitis: a disproportionality analysis in the FAERS database.XLSX

Objective: This study aimed to investigate the potential association between biological disease-modifying antirheumatic drugs (bDMARDs) and pericarditis and uncover relevant clinical characteristics in ankylosing spondylitis (AS).Methods: Reports of pericarditis recorded in the FDA Adverse Event Reporting System (FAERS) (January 2004–December 2022) were identified through the preferred term “pericarditis.” Demographic and clinical characteristics were described, and disproportionality signals were assessed through the reporting odds ratio (ROR) and information component (IC). A significant signal was detected if the lower bound of IC (IC025) was more than zero.Results: We found 1,874 reports of pericarditis with bDMARDs (11.3% of cases with fatal outcomes). Adalimumab (IC025 3.24), infliximab (IC025 4.90), golimumab (IC025 5.40), certolizumab (IC025 5.43), etanercept (IC025 3.24), secukinumab (IC025 3.97), and ustekinumab (IC025 7.61) exhibit significant disproportionality signals compared to other medications in the FAERS database. After excluding pre-existing diseases and co-treated drugs that may increase the susceptibility of pericarditis, the disproportionality signal associated with infliximab, certolizumab, etanercept, secukinumab, and ustekinumab remained strong. Pericarditis cases associated with all bDMARDs were predominantly recorded in women aged 25–65 years.Conclusion: More reports of pericarditis were detected with AS patients on bDMARDs than with other drugs in the overall database. Further studies are warranted to investigate the underlying mechanisms and identify patient-related susceptibility factors, thus supporting timely diagnosis and safe(r) prescribing of bDMARDs.</p

V<i>ertebrodural Ligaments</i> as shown in the dissected specimens and the P45 sheet plastination.

<p>A: Posterolateral aspect of the superior cervical vertebral canal; B: Median sagittal P45 plastination sheet of the superior cervical vertebral canal; C: Superior aspect of the dura mater and the posterior arch of atlas; D: Posterolateral aspect of the dura mater and the atlantoaxial interspace. On dissecting the posterior arch of the atlas and the lamina of the axis bilaterally and reflecting from one side to another (A), the <i>vertebrodural ligament</i> (VDL) was exposed in the posterior epidural space, which connected the dura matter with the atlas, axis and atlantoaxial space, thus the VDL was subdivided into three parts: the atlantal part, the TBNL’s part and the axial part (A). The median sagittal P45 plastination sheet of the superior cervical vertebral canal also showed that VDL consisted of these three parts (B). These three parts of VDL merged with each other and ran down almost vertically in the posterior epidural space continuing to the dura mater just anterior to the lamina of the axis (A, B). When the posterior arch of the atlas was cut bilaterally and reflected posteriorly, the atlantal part of VDL was shown specially in superior aspect, which was coronally banded in shape (C). When the lamina of the axis was cut bilaterally and then reflected posteroinferiorly, the TBNL’s and axial parts of VDL were shown in a lateral view to protrude from the dura mater in the median sagittal position and extending to the atlantoaxial interspace and the lamina of axis (D). VDL, the <i>vertebrodural ligament</i>. V1, atlantal part. V2, TBNL’s part. V3, axial part. RCPmi, rectus capitis posterior minor; C1, posterior arch of atlas; TBNL, <i>to be named ligament</i>; C2, lamina of vertebral arch of axis; DM, dura mater; Occi, occipital bone; SC, spinal cord.</p

VDL has five types according to its different components.

<p>The <i>vertebrodural ligament</i> is located in the posterior epidural space at the level from atlas to axis (A). It is inserted into the dura mater providing the dura matter with additional thickness (A). On rotating the neck, the <i>vertebrodural ligament</i> draws the posterior part of the dura mater, slightly, to the lateral side. According to its various components, VDL was observed as comprising of five specific types. Type I was the balance type. This was the strongest type, which was thick in each of the three parts (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0103451#pone-0103451-g002" target="_blank">Figure 2</a> A, B). Type II was the secondary balance type with the V3 weaker or absent (B). Type III was the atlas dominant type. In this type, V1 was thicker while V2 and V3 were weaker (C). Type IV was the TBNL dominant type, in which V2 was stronger than the others (D, E). Type V was the weakest type with few connective fibers extending from the posterior wall of the spinal canal to the cervical dura mater. In this kind of specimen, the atlantoaxial interspace was closed by the atlantoaxial membrane (or yellow ligament), and therefore the TBNL could not extend from the interspace into the epidural space as a result of weakness of the VDL (F). ↑, <i>vertebrodural ligament</i>. ▴, the thick area of dura matter. DM, dura mater. SC, spinal cord. C2, axis. V1, atlantal part. V2, TBNL’s part. V3, axial part. TBNL, <i>to be named ligament</i>. EDS, epidural space. ↑↑, weakness of the VDL. ▴▴, the atlantoaxial membrane (or yellow ligament).</p

The <i>to be named ligaments</i> were shown in the dissected specimens and the P45 plastination sheets.

<p>A, C: Lateroposterior aspect of the nuchal ligament; B, D: Median sagittal section of the head-neck in a P45 plastination sheet. <i>To Be Named Ligament</i> (TBNL) within the nuchal ligament was formed by arcuate fibers (A, B). The arcuate fibers arose from the lower part of the posterior border of NL below the level of the spinal process of vertebra C3 (A, B), continuing anterosuperiorly crossing over the spinous process of axis and continuing into the atlantoaxial interspace (B). Its path continues traversing through the interspace and attaching to the posterior aspect of the cervical dura mater (B). The rectus capitis posterior minor (RCPmi) emitted a bundle of muscular fibers (↓) which were attached to TBNL (A). Another kind of TBNL within the nuchal ligament was formed by radiated fibers (C, D). The radiated fibers originated from the posterior border of the upper part of nuchal ligament opposite to the spinal processes of vertebrae C2 and C3. At this point the radiated fibers ran anteriorly to traverse through the atlantoaxial interspace and finally attached to the posterior aspect of the cervical dura mater (D). Additionally, the RCPmi emitted a bundle of muscular fibers (↓↓), which merged into TBNL before it enterd the atlantoaxial interspace (D). TBNL, <i>To Be Named Ligament</i>. NL, nuchal ligament. AF, arcuate fibers of TBNL. RF, radial fibers of TBNL. C1∼C7, first to seventh cervical vertebra; Occi, occipital bone; RCPma, rectus capitis posterior major; SC, splenus capitis.</p