Giant cell arteritis associated with PD-1 inhibition

A 50-year-old woman was referred to rheumatology for new onset polyarthralgia and headache. She had a history of metastatic lung adenocarcinoma and was started on treatment with the programmed death 1 receptor (PD-1) antagonist pembrolizumab 2 months prior. Examination revealed left temporal artery tenderness and hand synovitis. Investigations revealed enlarged temporal artery on ultrasound imaging. On steroid treatment, she had resolution of symptoms, but due to significant steroid side effects required methotrexate and her PD-1 antagonist therapy was continued in consultation with her oncologist. Her malignant disease has remained stable, and she has improved functional status.

499. Rapid and Sustained Decline in CXCL-10 (IP-10) Annotates Clinical Outcomes Following TNF-α Antagonist Therapy in Hospitalized Patients with Severe and Critical COVID-19 Respiratory Failure

Background TNFα and IFN-γ may synergize to induce cytokine-driven lethal hyperinflammation and immune exhaustion in COVID-19 illness. Methods To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥ 50 compared to baseline and sustained for 48 hours. Secondary endpoints included 28-day mortality, dynamic cytokine profiles (Human Cytokine 48-Plex Discovery Assay), secondary infections, duration of supplemental oxygen support and hospitalization. Consort diagram Hospitalized patients with SARS-COV2 infection and pneumonia that were referred to the infliximab-abda study team for evaluation. Results Patients were predominantly in critical respiratory failure (15/18, 83%), male (14/18, 78%), above 60 years (median 63 yrs, range 31-80), race-ethnic minorities (13/18, 72%), lymphopenic (13/18, 72%), steroid-treated (17/18, 94%), with a median ferritin of 1953ng/ml. Sixteen patients (89%) met the primary endpoint within a median of 4 days, 15/18 (83%) recovered from respiratory failure, and 14/18 (78%) were discharged in a median of 8 days and were alive at 28-day follow-up. Deaths among three patients ≥ 65 years age with pre-existing lung disease or multiple comorbidities were attributed to secondary lung infections. Mean plasma IP-10 levels declined sharply from 9183 pg/ml to 483 pg/ml at Day 3 and 146 pg/ml at Day 14/discharge. Significant declines in IFN-γ, TNFα, IL-27, IL-6 (baseline above 10pg/ml), CRP and ferritin were specifically observed at Day 3 whereas other cytokines were unaffected. Among 13 lymphopenic patients, six (46%) had resolution of lymphopenia by day 3, and 11 by day 14. CXCR3-ligand (IP-10 and CXCL-9) declines were strongly correlated among patients with lymphopenia reversal (Day 3, Pearson r: 0.98, p-value: 0.0006). Demographics and clinical characteristics Demographics, comorbidities, clinical features, inflammatory markers, and outcomes of 18 patients with COVID-19 respiratory failure treated with infliximab-abda between April and December 2020. Changes in oxygen support status following infliximab-abda treatment Colored bars indicate the maximal level of oxygen support for each individual following treatment with infliximab-abda. The status of the patient at last follow-up (discharged, alive or dead) is indicated. ECMO: extracorporeal membrane oxygenation Control of inflammatory markers and cytokines following infliximab therapy Values from individuals are connected with solid lines, with deceased individuals indicated in red. Statistics: n=18, paired ratio t-test compared to baseline; *: P<0.05, **: P<0.01, ***: P<0.001, ****: P<0.0001, n.s.: not significant. Conclusion Consistent with a central role of TNFα, the clinical and cytokine data indicate that infliximab-abda may rapidly abrogate pathological inflammatory signaling to facilitate clinical recovery in severe and critical COVID-19. Randomized studies are formally evaluating infliximab therapy in this context. Funding: National Center for Advancing Translational Sciences Disclosures All Authors: No reported disclosures

Placental polyp with arteriovenous malformation treated with a gonadotoropin-releasing hormone antagonist

A 35-year-old woman (gravida 1, para 0) underwent termination of pregnancy (ToP) at 12 weeks of gestation. One month after ToP, she experienced significant vaginal bleeding and the mass with blood flow was identified on imaging. The presence of a placental polyp with arteriovenous malformation (AVM) was suspected on transvaginal sonography and MRI. Since the bleeding had ceased when she visited our hospital, we decided to treat the placental polyp with AVM with gonadotropin-releasing hormone (GnRH) antagonist therapy instead of surgery. Two months after GnRH antagonist treatment, the mass and blood flow in the uterus disappeared. Menstruation resumed 1 month after the completion of treatment. In our case, we were able to successfully treat placental polyps with AVM using GnRH antagonist therapy.