Accurate identification of medicines used in adverse event reports is crucial for effective postmarketing safety surveillance. The US Food and Drug Administration's (FDA) four-letter suffix naming convention was designed to facilitate accurate biological product identification, but the extent to which these suffixes have been incorporated into biosimilar reporting remains unclear. We conducted a cross-sectional analysis of US adverse event reports for all 72 FDA-approved biosimilar products in the FDA Adverse Event Monitoring System (AEMS) received through August 31, 2025, evaluating the proportion of reports containing a four-letter suffix, proprietary name, or other manufacturer identifiers. Of 24,711 reports analyzed, 12.7% (n = 3126) contained a biosimilar suffix, whereas 98.2% (n = 24,264) contained a proprietary name and 82% reported the manufacturer name. Suffixes served as the sole product identifier in only 1.7% (n = 413). These suffix-only reports were distinct: more frequently submitted directly to FDA (86.2% vs. 15.0%), by healthcare professionals (73.3% vs. 59.0%), commonly originated from Veterans Affairs Medical Centers and specialty pharmacies and involved more serious outcomes (47.7% vs. 27.9%), suggesting certain organizational preferences favoring nonproprietary name reporting. The product distribution also differed, with adalimumab-aacf most common in suffix-only reports (18.9%) vs. infliximab-dyyb overall (21.1%). Manufacturer information was present in 42.6% of suffix-only reports. These results suggest FDA's nonproprietary naming convention has achieved limited implementation for biosimilars in AEMS reporting practices, and other information present in AEMS reports may be sufficient for accurately identifying biosimilar products.

Severe allergic reactions can occur when biotherapeutics containing the carbohydrate antigen galactose-α-1,3-galactose (α-Gal) are administered. The detection of α-Gal-containing N-glycans is a challenging task due to the presence of non-α-Gal-containing isomers. This study evaluates the ability of different analytical approaches to detect an α-Gal glycan in the presence of a non-α-Gal isomer. Cetuximab is known to contain N-glycans bearing the α-Gal epitope and was chosen for the study. N-glycans released from Cetuximab were analyzed using the HILIC-MS/MS system. HILIC-MS/MS successfully separated and identified α-Gal species when the Galactose number exceeded the antenna number. However, this system could not identify α-Gal species when the Galactose number equals the antenna number. A High-Resolution Ion Mobility Spectrometer (IMS) was also evaluated and found to resolve isomeric α-gal/non-α-gal isomeric glycans. The study demonstrates the utility of the IMS-MS system by detecting immunogenic glycans in the presence of their non-α-Gal isomers. To our knowledge, this is the first time this specific immunogenic pair of glycan isomers has been resolved in a biotherapeutic, which was enabled by a high-resolution IMS separation.

Post-translational modifications (PTMs), such as glycation, can be introduced during the manufacturing and storage of therapeutic proteins, including monoclonal antibodies (mAbs). Glycation modification may alter the safety and efficacy of therapeutic drugs, thus necessitating their accurate quantification. Relative quantitation is typically performed by comparing the peak area of the glycated peptide with that of its unmodified counterparts. The accuracy of this method depends on the unmodified and modified peptides having similar ionization efficiencies, as well as on the selection of the native peptide used for quantitation. We propose using non-glycated, heavy-isotope-labeled proteins to quantify glycation. The heavy isotope-labeled proteins can provide both the relative and absolute level of glycation by comparing the peak area of the unmodified tryptic peptides to that of the heavy isotope-labeled variants. To develop this approach, glycation was intentionally induced in an immunoglobulin (IgG) to have detectable glycation. A heavy isotope-labeled variant of the IgG (containing 13C and 15N lysine and arginine residues) was added to serve as an internal standard. Further, this mixture was subjected to trypsin digestion, and a bottom-up approach using Hydrophilic Interaction Liquid Chromatography (HILIC)-MS was performed. The light/heavy ratio of tryptic peptides with and without a glycation site in the forced glycation sample was monitored. Any decrease in the light/heavy ratio of peptides containing a glycation site relative to the expected ratio was attributed to the production of glycated variants. Glycation quantitation in IgGs such as Adalimumab (IgG1) and Natalizumab (IgG4) was performed. We expect this approach will apply to other PTMs.

Switching from reference biologics to biosimilars usually occurs for non-medical reasons, such as cost-driven formulary changes. However, despite biosimilars having the same efficacy and similar safety profiles as their reference products, some patients discontinue treatment and 'switchback' to the reference product.

Hidradenitis suppurativa is increasingly recognized as a systemic inflammatory disease with an established overlap with spondyloarthritis. Axial spondyloarthritis is usually suspected when patients report inflammatory back pain, which remains the entry feature of the ASAS axial spondyloarthritis classification criteria. We report a 31-year-old man with Hurley stage II hidradenitis suppurativa who presented with Achilles enthesitis supported by point-of-care ultrasound but denied any current or previous back pain lasting 3 months or longer, including inflammatory back pain and alternating buttock pain, prolonged morning stiffness, peripheral arthritis, dactylitis, uveitis, psoriasis, and gastrointestinal symptoms. During workup for asymptomatic microscopic hematuria, computed tomography of the pelvis incidentally showed bilateral sacroiliac joint abnormalities that prompted dedicated imaging. Magnetic resonance imaging of the sacroiliac joints showed findings meeting the consensus definition of active sacroiliitis, with bilateral subchondral bone marrow edema and early structural changes. The patient was human leukocyte antigen B27 positive, had elevated inflammatory markers, and had a first-degree family history of ankylosing spondylitis. Although the ASAS axial spondyloarthritis classification criteria were not fulfilled because the required history of back pain lasting 3 months or longer was absent, the patient fulfilled the ASAS peripheral spondyloarthritis classification criteria based on current Achilles enthesitis together with HLA-B27 positivity and sacroiliitis on imaging. Converging clinical, imaging, immunogenetic, and familial features supported a clinical diagnosis of spondyloarthritis associated with hidradenitis suppurativa. Adalimumab was started using the licensed hidradenitis suppurativa regimen. At 6 months, calcaneal tenderness and skin lesions had improved, inflammatory markers had normalized, and follow-up imaging showed substantial reduction in bone marrow edema. This case suggests that axial inflammation in hidradenitis suppurativa may be under-recognized when assessment relies exclusively on patient-reported back pain. Sacroiliac MRI should not be used routinely in all patients with hidradenitis suppurativa and enthesitis-like symptoms but may be considered after rheumatologic assessment when multiple clinical, laboratory, familial, or incidental imaging features collectively raise suspicion of spondyloarthritis.

Ulcerative colitis (UC) is a chronic inflammatory disease that primarily affects the colon. Tumor necrosis factor-α inhibitors (like adalimumab) are effective agents for UC. However, loss of response may occur. Proactive therapeutic drug monitoring involves measuring drug levels at regular intervals in patients in remission to maintain therapeutic concentrations and potentially prevent loss of response.