Recommendations for the management of secondary hypogammaglobulinaemia due to B cell targeted therapies in autoimmune rheumatic diseases

Abstract

Objectives The association of B cell targeted therapies with development of hypogammaglobulinaemia and infection is increasingly recognized. Our aim was to develop consensus recommendations for immunoglobulin replacement therapy for management of hypogammaglobulinaemia following B cell targeted therapies in autoimmune rheumatic diseases. Methods A modified Delphi exercise involved a 17-member Taskforce committee, consisting of immunologists, rheumatologists, nephrologists, haematologists, a gastroenterologist, an immunology specialist nurse and a patient representative. The first round identified the most pertinent topics to address in the recommendations. A search string was agreed upon for the identification of publications in PubMed focusing on these areas, for a systematic literature review. Original data was presented from this review to the Taskforce committee. Recommendations from the British Society for Rheumatology, the UK Department of Health, EULAR, the ACR, and the American Academy of Allergy, Asthma, and Immunology were also reviewed. The evidence was discussed in a face-to-face meeting to formulate recommendation statements. The levels of evidence and statements were graded according to Scottish Intercollegiate Guidelines Network methodology. Results Three overarching principles, eight recommendation statements and a research agenda were formulated. The Taskforce committee voted on these statements, achieving 82–100% agreement for each recommendation. The strength of the recommendations was restricted by the low quality of the available evidence, with no randomized controlled trial data. The recommendations cover risk factors, monitoring, referral for hypogammaglobulinaemia; indications, dosage and discontinuation of immunoglobulin replacement therapy. Conclusion These are the first recommendations specifically formulated for B cell targeted therapies related to hypogammaglobulinaemia in autoimmune rheumatic diseases. The recommendations are to aid health-care professionals with clinical decision making for patients with hypogammaglobulinaemia.

Re: ‘ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies’ by Mikulska et al.

“…In appropriate cases, we recommend detailed clinical assessment of hypogammaglobulinemic patients to consider whether a trial of IGRT is warranted. Consideration of IGRT is mentioned in the ESGICH consensus document section on anti-CD19 agents, and our evidence indicates that this consideration should be applied to anti-CD20 agents [1,2].…”

“…from infection (odds ratio ¼ 21.1; 95% confidence interval, 1.1e404.1). In rheumatoid arthritis, patients with IgG <6g/L were at higher risk of severe infections (26.1% vs. 6.3%, p 0.033) [2].…”

“…We stress the importance of early vaccination for appropriate organisms in AIRD patients because for 1 to 6 months after anti-CD20 treatment, there is impairment of antibody responses to vaccinations with important respiratory pathogens (e.g. influenza, Streptococcus pneumoniae and Haemophilus influenzae), as mentioned within the consensus document [1,2].…”

“…However, in the article, particularly with respect to anti-CD20 agents, we think that the contribution of hypogammaglobulinaemia to infection risk may have been underestimated [1]. We have recently published recommendations for the management of secondary hypogammaglobulinaemia due to B-celletargeted therapies (BCTT) in autoimmune rheumatic diseases (AIRD) [2]. In addition to the infective risks, the development of hypogammaglobulinaemia complicates the future use of an effective therapy in AIRD.…”

“…Our taskforce committee recommended baseline and then regular monitoring of immunoglobulin levels once every 6 to 12 months [2]. In appropriate cases, we recommend detailed clinical assessment of hypogammaglobulinemic patients to consider whether a trial of IGRT is warranted.…”