Immunosuppressive therapy and humoral response to third mRNA COVID-19 vaccination with a six-month interval in rheumatic disease patients.

OBJECTIVES: To evaluate the long-term impact of immunosuppressive therapeutic agents on antibody response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with autoimmune rheumatic diseases (AIRD) in order to propose a strategy for annual vaccination. METHODS: This prospective multicentre cohort study evaluated the humoral response to second and third BNT162b2 and/or mRNA-1273 vaccines in 382 Japanese AIRD patients classified into 12 different medication groups and in 326 healthy controls (HCs). The third vaccination was administered six months after the second vaccination. Antibody titres were measured using the Elecsys Anti-SARS-CoV-2 S assay. RESULTS: The seroconversion rate and antibody titres were lower in AIRD patients than in HCs 3-6 weeks after the second vaccination and 3-6 weeks after the third vaccination. Seroconversion rates were <90% after the third vaccination in patients receiving mycophenolate mofetil and rituximab. Antibody levels after the third vaccination were significantly lower in the groups prescribed TNF inhibitor with or without methotrexate, abatacept and rituximab or cyclophosphamide than those of HCs in a multivariate analysis adjusting for age, sex, and glucocorticoid dosage. The third vaccination induced an adequate humoral response in patients treated with sulfasalazine, bucillamine, methotrexate monotherapy, iguratimod, interleukin-6 inhibitors or calcineurin inhibitors including tacrolimus. CONCLUSIONS: Repeated vaccinations in many immunosuppressed patients produced antibody responses similar to those observed in HCs. In contrast, annual vaccination in patients receiving TNF inhibitors, abatacept, mycophenolate mofetil and rituximab may require caution.

Antibody response to SARS-CoV-2 mRNA vaccines in patients with rheumatic diseases in Japan: Interim analysis of a multicentre cohort study.

OBJECTIVES: To evaluate the impact of medication on antibody response to severe acute respiratory syndrome coronavirus-2 mRNA vaccines in Japanese patients with rheumatic diseases. METHODS: This prospective multicentre cohort study evaluated the humoral response in 12 different medication groups. Antibody levels before the first vaccination and 3-6 weeks after the second vaccination were measured using the Elecsys Anti-SARS-CoV-2 S assay. Statistical analysis included comparing antibody titres among the different medication groups using the Kruskal-Wallis test followed by the Bonferroni-Dunn test and multiple linear regression analysis. RESULTS: 295 patients were analysed. The seroconversion rate was 92.2% and the median antibody titre was 255 U/ml (interquartile range, 34.1-685) after the second mRNA vaccination. Antibody levels were significantly lower in the groups treated with Tumour necrosis factor inhibitor with methotrexate, abatacept, mycophenolate mofetil (MMF), MMF or mizoribine combined with calcineurin inhibitor, and rituximab or cyclophosphamide compared with those treated with sulfasalazine and/or bucillamine or calcineurin inhibitor (p < 0.01). The correlation between antibody titre and treatment was significant after adjusting for age, gender, and glucocorticoid dose (p < 0.01). CONCLUSIONS: Additional early vaccination is required in patients treated with Tumour necrosis factor inhibitor and methotrexate, abatacept, MMF, MMF or mizoribine combined with calcineurin inhibitor and rituximab or cyclophosphamide.

A case in which baricitinib was effective for both rheumatoid arthritis and essential thrombocythemia.

We experienced a case of rheumatoid arthritis and JAK2V617F mutation-positive essential thrombocythemia treated with baricitinib. The patient was a 72-year-old male. He was diagnosed with rheumatoid arthritis at a local clinic in April 2018. Methotrexate (MTX) was started and the dose was increased to 16 mg/week. In October of the same year, anaemia was observed and MTX was reduced, but anaemia progressed. Blood tests showed pancytopenia, and he was referred to Rheumatology on suspicion of drug-induced pancytopenia. Pancytopenia improved with discontinuation of MTX and administration of folic acid. His platelet count was markedly increased to 1,400,000/µl at one point, decreased to 400,000/µl, and then gradually increased to 700,000-1,000,000/µl. Despite taking an antiplatelet drug, he developed cerebral infarction in June 2019. The JAK2V617F mutation was noted, and he was diagnosed with essential thrombocythemia. Hydroxycarbamide was started, but the effect was insufficient. Baricitinib, a JAK1/2 inhibitor indicated for rheumatoid arthritis, was started in August with the expectation that it would also be effective for essential thrombocythemia. The platelet count decreased to ∼400,000-600,000 cells/µl, and a decrease in the C-reactive protein level and the improvement of arthritis were noted. We report this case because it is considered to be a valuable case, suggesting that baricitinib may be effective for essential thrombocythemia.

A Case of Rapidly Progressing Hepatocellular Carcinoma after Administration of JAK Inhibitors to Treat Rheumatoid Arthritis.

We report a case of rapidly progressing hepatocellular carcinoma after administration of Janus kinase (JAK) inhibitors to treat rheumatoid arthritis. A 76-year-old man was referred to our Department for pain in multiple joints and was diagnosed with rheumatoid arthritis. Blood tests revealed elevated hepatobiliary enzymes, but various tests revealed no signs suggestive of malignancy. He took baricitinib for 2 months followed by tofacitinib for 4 months. After that, he was diagnosed with hepatocellular carcinoma based on imaging findings and elevated tumor markers. This case showed the possibility of a causal relationship between JAK inhibitors and malignancy.

Clozapine-induced antineutrophil cytoplasmic antibody-associated vasculitis: a case report.

Clozapine is the most effective antipsychotic medication for refractory schizophrenia, but it has many possible serious side effects, including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the rare case reports available have not presented sufficient characteristic features of drug-induced AAV. Herein, we report a case of a 48-year-old Japanese woman with schizophrenia who presented with fever, arthralgia, myalgia and skin rash after 2 years of clozapine treatment. Her C-reactive protein (CRP) level increased, myeloperoxidase ANCA was positive and skin biopsy revealed leukocytoclastic vasculitis. Initially, steroid administration achieved remission, but her symptoms and high CRP levels relapsed every time the steroid dosage was tapered down. Upon discontinuation of clozapine, her symptoms and elevated CRP level immediately improved and the steroid was successfully tapered and discontinued. This outcome suggested that clozapine was the main cause of AAV.