Full Papers
Pneumocystis jirovecii pneumonia prophylaxis in rare systemic autoimmune rheumatic diseases: a systematic review of randomised controlled trials within the European Reference Network on Connective Tissue and Musculoskeletal Diseases
M. Vandycke1, Y. Piette2, S. Aguilera3, C. Cardamone4, D. Carvalho5, L. Gatti6, D. Marinello7, E. Marrani8, M. Mosca9, R. Talarico10, M. Cutolo11, V. Smith12
- Department of Rheumatology, Ghent University Hospital, Ghent; and Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium.
- Department of Rheumatology, Ghent University Hospital, Ghent; Department of Internal Medicine, Ghent University Hospital, Ghent; Department of Rheumatology, AZ Sint-Jan Brugge AV, Bruges, Belgium; and European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET).
- European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET); and Spanish Association for Antiphospholipid Syndrome (SAF España), Elche, Spain.
- European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET); and Clinical Immunology and Rheumatology Unit, Department of Internal Medicine, University Hospital San Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy.
- European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET); Rheumatology Department, Hospital Dr. Nélio Mendonça, SESARAM EPERAM, Madeira; and Rheumatology Department, Unidade Local de Saúde de Santa Maria, Lisboa, Portugal.
- European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET); and Rheumatology Unit, Meyer Children's Hospital IRCCS, Florence, Italy.
- European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET); and Rheumatology Unit, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Italy.
- European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET); and Rheumatology Unit, Meyer Children's Hospital IRCCS, Florence, Italy.
- European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET); and Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.
- European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET); and Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.
- European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET); and Laboratory of Experimental Rheumatology and Academic Division of Clinical Rheumatology, Department of Internal Medicine and Medical Specialties (Di.M.I.), IRCCS Ospedale Policlinico San Martino, University of Genova, Italy.
- Department of Rheumatology, Ghent University Hospital, Ghent; Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium; European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ERN ReCONNET); and Molecular Immunology and Inflammation Unit, VIB Inflammation Research Center (IRC), Ghent, Belgium. vanessa.smith@ugent.be
CER20074
Full Papers
PMID: 43006904 [PubMed]
Received: 25/04/2026
Accepted : 03/09/2026
In Press: 10/11/2026
Abstract
OBJECTIVES:
To systematically evaluate the efficacy and safety of Pneumocystis jirovecii pneumonia (PJP) prophylaxis in patients with non-rheumatoid arthritis systemic autoimmune rheumatic diseases (non-RA SARD) and to identify high-risk subgroups benefiting from primary prophylaxis.
METHODS:
This systematic review followed PRISMA 2020 guidelines. A comprehensive search of MEDLINE, Embase, Cochrane Central, and Scopus was conducted. We exclusively included randomised controlled trials (RCTs) with ≥6 months of follow-up comparing chemoprophylaxis against placebo or no intervention in non-RA SARD populations.
RESULTS:
From 1,974 screened records, one RCT met the inclusion criteria. This open-label trial investigated trimethoprimsulfamethoxazole versus no intervention in patients with systemic lupus erythematosus receiving low-level immunosuppression. No PJP cases were recorded; however, the trial was terminated prematurely due to adverse drug reactions (14.3%). The risk of bias was considered high, and the certainty of evidence (GRADE) was rated as very low.
CONCLUSIONS:
This systematic review reveals a profound lack of high-level evidence for PJP prophylaxis in non-RA SARDs, identifying only a single, underpowered RCT with a high risk of bias. Future research should transition from a universal management approach to a risk-stratified model that prioritises high-risk periods characterised by induction therapy or high-dose glucocorticoid use (≥20–30 mg/day) and underlying risk factors such as pre-existing interstitial lung disease. In the absence of definitive trial data, leveraging the multidisciplinary expertise of the European Reference Networks is essential to harmonise care and develop expert-led clinical guidelines that optimise patient safety across Europe.
