这是一系列来自患者的零星文章中的最后一篇，他们的经历为医生提供了生动教程。关于"你的患者在想什么"系列的更多信息，请联系患者编辑Rosamund Snow (rsnow@bmj.com)。

Antiphospholipid syndrome

Reduced humoral response to mRNA SARS-CoV-2 BNT162b2 vaccine in kidney transplant recipients without prior exposure to the virus.

Monoclonal antibodies that target CD20 expressing B cells represent an important new treatment option for patients with multiple sclerosis (MS). B-cell-depleting therapy is highly effective against relapsing forms of the disease and is also the first treatment approach proven to protect against disability worsening in primary progressive MS. Moreover, evolving clinical experience with B-cell therapy, combined with a more sophisticated understanding of humoral immunity in preclinical models and in patients with MS, has led to major progress in deciphering the immune pathogenesis of MS. Here, we review the nuanced roles of B cells in MS autoimmunity, the clinical data supporting use of ocrelizumab and other anti-CD20 therapies in the treatment of MS, as well as safety and practical considerations for prescribing. Last, we summarize remaining unanswered questions regarding the proper role of anti-CD20 therapy in MS, its limitations, and the future landscape of B-cell-based approaches to treatment. Ann Neurol 2018;83:13-26.

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B-cell Therapy for Multiple Sclerosis: Entering an era.

https://iris.unige.it/bitstream/11567/893681/2/9Mikulska%20M_Mikulska.pdf

ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: An infectious diseases perspective (agents targeting lymphoid cells surface antigens [I]: CD19, CD20 and CD52)

Objective To determine whether a 2-week methotrexate (MTX) discontinuation after vaccination improves the efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis (RA). Methods In this prospective randomised parallel-group multicentre study, patients with RA on stable dose of MTX were randomly assigned at a ratio of 1:1 to continue MTX or to hold MTX for 2 weeks after 2016–2017 quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B-Yamagata and B-Victoria. The primary outcome was frequency of satisfactory vaccine response, defined as greater than or equal to fourfold increase of haemagglutination inhibition (HI) antibody titre at 4 weeks after vaccination against ≥2 of four vaccine strains. Secondary endpoints included seroprotection (ie, HI titre ≥1:40) rate, fold change in antibody titres. Results The modified intention-to-treat population included 156 patients in the MTX-continue group and 160 patients in the MTX-hold group. More patients in MTX-hold group achieved satisfactory vaccine response than the MTX-continue group (75.5% vs 54.5%, p Conclusions A temporary MTX discontinuation for 2 weeks after vaccination improves the immunogenicity of seasonal influenza vaccination in patients with RA without increasing RA disease activity. Trial registration NCT02897011.

https://ard.bmj.com/content/annrheumdis/77/6/898.full.pdf

Impact of temporary methotrexate discontinuation for 2 weeks on immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis: A randomised clinical trial

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.

https://ard.bmj.com/content/annrheumdis/80/10/1255.full.pdf

Impact of disease-modifying antirheumatic drugs on vaccine immunogenicity in patients with inflammatory rheumatic and musculoskeletal diseases.

Patients with rheumatoid arthritis are highly vulnerable to infections because of abnormalities in their immune system, and because of immunosuppressive effects of their medications. Vaccinations in this population are complicated by disease-modifying antirheumatic drugs, which also modulate or suppress the immune system and potentially decrease the immunogenicity and efficacy of the vaccines. We review the available data regarding the impact of rheumatoid arthritis therapy on the immunogenicity of various common vaccines. We also review rheumatoid arthritis-specific vaccination recommendations, live vaccine safety concerns, and current gaps in our understanding of these issues."

Vaccines and Disease-Modifying Antirheumatic Drugs: Practical Implications for the Rheumatologist.

Do tumor necrosis factor inhibitors increase cancer risk in patients with chronic immune-mediated inflammatory disorders?

Patients with rheumatoid arthritis (RA) suffer an increased burden of infectious disease-related morbidity and mortality and have twice the risk of acquiring a severe infection compared to the general population. This increased risk is not only a result of the autoimmune disease but is also attributed to the immunosuppressive therapies that are commonly used in this patient population. Given the increase in infection-related risks in RA, there is great interest in mitigating such risk. A number of vaccines are available to the rheumatologist, with a handful that are of importance for RA patients in the United States. The goal of this paper is to highlight the most recent literature on the key vaccines and the specific considerations for the rheumatologist and their RA patients, with a particular focus on influenza, pneumococcal, and herpes zoster vaccines. It is important for rheumatologist to understand and be aware of which vaccines are live and what potential contraindications exist for giving vaccines to RA patients.

Vaccinations for rheumatoid arthritis.

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.

/pdf/tofacitinib-as-a-steroid-sparing-therapy-in-pulmonary-55hrgmr783.pdf

Marcia A Friedman

Papers

Impact of disease-modifying antirheumatic drugs on vaccine immunogenicity in patients with inflammatory rheumatic and musculoskeletal diseases.

Vaccines and Disease-Modifying Antirheumatic Drugs: Practical Implications for the Rheumatologist.

Do tumor necrosis factor inhibitors increase cancer risk in patients with chronic immune-mediated inflammatory disorders?

Vaccinations for rheumatoid arthritis.

Tofacitinib as a Steroid-Sparing Therapy in Pulmonary Sarcoidosis, an Open-Label Prospective Proof-of-Concept Study.