Marcia Alwina Friedman

Objective: To compare the efficacy of abatacept to placebo for the treatment of relapsing, nonsevere granulomatosis with polyangiitis (GPA). Methods: In this multicenter trial, eligible patients with relapsing, nonsevere GPA were randomized to receive abatacept 125 mg subcutaneously once a week or placebo, both together with prednisone 30 mg/day (or equivalent), tapered and discontinued at week 12. Patients already taking methotrexate, azathioprine, mycophenolate, or leflunomide continued this medication at a stable dose. Patients achieving remission remained on their randomized assignment until relapse, early termination, or the common close date 12 months after enrollment of the last patient. Those who had a nonsevere relapse, had nonsevere worsening, or were not in remission by month 6 had the option to receive open‐label abatacept. The primary end point was the rate of treatment failure, defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0 or 1 by six months. Results: Sixty‐five patients were randomized; 34 received abatacept and 31 received placebo. No statistical difference in the treatment failure rate was found between those who received abatacept and those who received placebo ( P = 0.853). Treatment with abatacept did not demonstrate any statistical difference from placebo in key secondary end points, including time to full remission (BVAS/WG = 0), duration of glucocorticoid‐free remission, relapse severity, prevention of damage, and patient‐reported quality‐of‐life outcomes. There was no difference in the frequency or severity of adverse events between treatment arms, including infection. Conclusion: In patients with relapsing, nonsevere GPA, abatacept did not reduce the risk of relapse, severe worsening, or failure to achieve remission.

Key Points: Skin IL-9, calprotectin, and KIR gene expression may be predictive of subsequent kidney involvement in patients with IgAV. Histologically similar patients with IgAN, IgAV, and IgA-IRGN can be distinguished by their immune transcriptomes. Kidney biopsies from patients with IgA-IRGN are enriched for transcripts involved in granulocyte chemotaxis. Background: IgA vasculitis (IgAV), IgA nephropathy (IgAN), and IgA-dominant infection-related glomerulonephritis (IgA-IRGN) have shared histopathologic features, but differences in clinical management and prognosis. The most serious IgAV organ involvement is in the kidneys (IgAV nephritis). In this study, we hypothesized that targeted immune transcript profiling could aid in (1) predicting the development of IgAV nephritis in patients with cutaneous IgAV and (2) differentiating IgAN, IgAV, and IgA-IRGN. Methods: RNA was extracted from 24 formalin-fixed paraffin-embedded tissue specimens (16 kidney, 8 skin) from 21 patients with IgAV nephritis (n=7), IgAN (n=5), and IgA-IRGN (n=4), and IgAV skin biopsies from patients with (n=3) and without (n=5) IgAV nephritis. Differential gene expression and gene set enrichment analysis were performed on a total of 594 transcripts (Nanostring immunology panel) profiled using the nCounter system. Results: Skin biopsies in patients with IgAV who develop kidney involvement exhibit reduced S100A8/S100A9, IL9, and killer cell immunoglobulin-like receptor expression. The kidney tissue immune transcriptomes of IgAN, IgAV, and IgA-IRGN are largely overlapping. IgA-IRGN kidney biopsies are, however, uniquely enriched for transcripts involved in granulocyte chemotaxis. Conclusion: This study identifies immune transcript signatures that may predict IgAV nephritis in skin biopsies and distinguish IgA-IRGN from IgAN and IgAV in kidney biopsies.

This report describes a highly unusual and refractory case of proteinase-3–positive antineutrophil cytoplasmic autoantibody–associated vasculitis, which was associated with marked eosinophilia and only achieved remission after interleukin-5 blockade was added to maximal induction therapy. The patient was a healthy 18-year-old woman who presented with scleritis, otitis, constitutional symptoms, skin and mucosal lesions, and diffuse alveolar haemorrhage and found to have refractory eosinophilia of unclear aetiology. The case did not meet classification criteria for a diagnosis of granulomatosis with polyangiitis or eosinophilic granulomatosis with polyangiitis. Despite induction therapy with glucocorticoids, cyclophosphamide, and rituximab, she did not achieve remission or normalisation of eosinophilia until the addition of mepolizumab, which corresponded to the suppression of peripheral blood eosinophils and clinical remission. This case highlights the limitations of classification criteria and success of interleukin-5 in a multimodal treatment of severe vasculitis with eosinophilia.

Patients with rheumatic diseases are at increased risk of infectious complications; vaccinations are a critical component of their care. Disease-modifying antirheumatic drugs may reduce the immunogenicity of common vaccines. We will review here available data regarding the effect of these medications on influenza, pneumococcal, herpes zoster, SARS-CoV-2, hepatitis B, human papilloma virus and yellow fever vaccines. Rituximab has the most substantial impact on vaccine immunogenicity, which is most profound when vaccinations are given at shorter intervals after rituximab dosing. Methotrexate has less substantial effect but appears to adversely impact most vaccine immunogenicity. Abatacept likely decrease vaccine immunogenicity, although these studies are limited by the lack of adequate control groups. Janus kinase and tumour necrosis factor inhibitors decrease absolute antibody titres for many vaccines, but do not seem to significantly impact the proportions of patients achieving seroprotection. Other biologics (interleukin-6R (IL-6R), IL-12/IL-23 and IL-17 inhibitors) have little observed impact on vaccine immunogenicity. Data regarding the effect of these medications on the SARS-CoV-2 vaccine immunogenicity are just now emerging, and early glimpses appear similar to our experience with other vaccines. In this review, we summarise the most recent data regarding vaccine response and efficacy in this setting, particularly in light of current vaccination recommendations for immunocompromised patients.

This is a prospective, open-label, proof-of-concept study of tofacitinib, a Janus kinase inhibitor, as a steroid-sparing therapy in corticosteroid-dependent pulmonary sarcoidosis. Five patients with corticosteroid-dependent pulmonary sarcoidosis were treated with tofacitinib 5 mg twice daily. The primary endpoint was a ≥ 50% reduction in corticosteroids at week 16 with no worsening in pulmonary function or respiratory symptoms. 60% of patients (3/5) met the primary endpoint. One patient was lost to follow up prior to steroid taper, and another was withdrawn due to worsening of known neurosarcoidosis. The three patients who met the primary endpoint each tapered to ≤ 5 mg/day prednisone, respiratory symptoms improved, and spirometry remained stable. In this proof-of-concept study, the addition of a JAK-inhibitor allowed 60% of patients with pulmonary sarcoidosis to successfully taper corticosteroids. JAK-inhibitors are a promising therapy for pulmonary sarcoidosis, which require further investigation in randomized trials. Trial Registration clinicaltrials.gov NCT03793439; registered Jan 4, 2019.

Observational data suggest there may be an association between rituximab and severe COVID-19 outcomes.1–3 Anti-CD20 therapies impair humoral response, theoretically increasing the risk of prolonged SARS-CoV-2 infection and shedding, as well as subsequent reinfection. Here, we report a patient with granulomatosis with polyangiitis (GPA) being treated with rituximab who appears to have developed recurrent SARS-CoV-2 infections in the setting of high-risk employment and on recovery ultimately had no detectable SARS-CoV-2 IgG antibodies. This case highlights a potential risk of rituximab in patients with rheumatic disease, which will become especially relevant as rituximab may impair the immunogenicity of SARS-CoV-2 vaccines.

This is a prospective, open-label, proof-of-concept study of tofacitinib, a Janus kinase inhibitor, as a steroid sparing therapy in corticosteroid-dependent pulmonary sarcoidosis. 5 patients with corticosteroid-dependent pulmonary sarcoidosis were treated with tofacitinib 5 mg twice daily. The primary endpoint was a ≥50% reduction in corticosteroids at week 16 with no worsening in pulmonary function or respiratory symptoms. 60% of patients (3/5) met the primary endpoint. One patient was lost to follow up prior to steroid taper, and another was withdrawn due to worsening of known neurosarcoidosis. The three patients who met the primary endpoint each tapered to ≤5 mg/day prednisone, respiratory symptoms improved, and spirometry remained stable. In this proof-of-concept study, the addition of a JAK-inhibitor allowed 60% of patients with pulmonary sarcoidosis to successfully taper corticosteroids. JAK-inhibitors are a promising therapy for pulmonary sarcoidosis, which require further investigation in randomized trials.Trial Registration: clinicaltrials.gov NCT03793439; registered Jan 4, 2019

Aim: Idiopathic granulomatous mastitis (IGM) is an enigmatic inflammatory breast disorder. IGM responds to immunomodulatory treatment and may be associated with systemic manifestations such as arthritis and erythema nodosum. These patients are increasingly referred to rheumatologists for management, but IGM is rarely discussed in the rheumatology literature. The objective of this report is to familiarize rheumatologists with the treatment and systemic manifestations of IGM. We report here a case series of IGM at our institution, and a literature review of IGM treated with methotrexate (MTX).Method: Patients with IGM at our institution were identified and described using a retrospective chart review. A literature review of PubMed and Google Scholar identified studies of IGM patients treated with MTX.Results: We identified 28 IGM patients at our institution. Inflammatory arthritis/arthralgia were present in four patients (14%), and five patients (18%) had erythema nodosum. Patients treated with MTX had the highest rates of relapse‐free remission; relapse‐free remission occurred in four of the five (80%) MTX‐treated patients, compared with 5 of 12 (42%) patients treated with steroids alone, and two or three (66%) patients treated with steroids and surgery. In the literature review, 116 patients treated with MTX were identified, and the rate of relapse‐free remission ranged from 58% to 100%. Arthritis/arthralgia and erythema nodosum were more common at our institution than reported in the literature.Conclusion: Methotrexate is a promising treatment for IGM. Arthritis/arthralgias and erythema nodosum may be under‐recognized when IGM patients are managed outside rheumatology. Prospective studies are needed to characterize clinical features and optimum treatment of IGM.