GeneralREVIEW ARTICLE

Glucocorticoid use in rheumatoid arthritis patients and the onset of pneumonia: a systematic review and meta-analysis

Kawther N. Elsouri, BS, MS; Vania Arboleda, BS; Lynn Basbous, BS; Samantha Heiser, BS, MS; Dylon P. Collins, BS; Philip Ragusa, BS; Courney Baxter, BS; Dominick Cabrera, BS, MS; Tanisha Akhand, BS; Evan Stermer, BS, MS; Kiran Sharma, BS; Charmaine Seguro, BS, MS; Patrick Hardigan, PhD; Marc Kesselman, DO; and Michelle Demory Beckler, PhD
Notes and Affiliations
Notes and Affiliations

Received: August 21, 2022

Accepted: November 29, 2022

Published: January 25, 2023

  • Kawther N. Elsouri, BS, MS, 

    Nova Southeastern University Kiran Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

  • Vania Arboleda, BS, 

    Nova Southeastern University Kiran Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

  • Lynn Basbous, BS, 

    American University of Beirut, Beirut, Lebanon

  • Samantha Heiser, BS, MS, 

    William Carey University College of Osteopathic Medicine, Hattiesburg, MS, USA

  • Dylon P. Collins, BS, 

    Nova Southeastern University Kiran Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

  • Philip Ragusa, BS, 

    Nova Southeastern University Kiran Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

  • Courney Baxter, BS, 

    Nova Southeastern University Kiran Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

  • Dominick Cabrera, BS, MS, 

    Nova Southeastern University Kiran Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

  • Tanisha Akhand, BS, 

    Nova Southeastern University Kiran Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

  • Evan Stermer, BS, MS, 

    Nova Southeastern University Kiran Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

  • Kiran Sharma, BS, 

    Nova Southeastern University Kiran Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

  • Charmaine Seguro, BS, MS, 

    Nova Southeastern University Kiran Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

  • Patrick Hardigan, PhD, 

    Nova Southeastern University Kiran Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA

  • Marc Kesselman, DO, 

    Nova Southeastern University Kiran Patel College of Osteopathic Medicine, Fort Lauderdale, FL, USA

  • Michelle Demory Beckler, PhD, 

    Nova Southeastern University Kiran Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA

J Osteopath Med; 123(4): 179-186
Abstract

Context: Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying antirheumatic drugs (DMARDs), have been associated with pulmonary infections. These types of infections (specifically pneumonia) can be detrimental to RA patients. This leads providers to utilize other treatment modalities such as glucocorticoids (GCs). GCs are commonly utilized to treat RA; however, the role of GCs in the onset of pneumonia in RA patients is not fully understood.

Objectives: The goal of this study was to systematically review and statistically analyze pooled data documenting pneumonia as an adverse event in RA patients on DMARDs as a monotherapy vs RA patients on DMARDs and GCs as combination therapy utilizing the Population, Intervention, Comparison, and Outcomes (PICO) framework.

Methods: On August 1, 2021, a search was conducted and completed on six databases: Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, International Pharmaceutical Abstracts (IPA), and ClinicalTrials.gov. A total of 12 researchers were involved with the search and screening of articles (K.E., P.R.; V.A., D.P.C.; C.B., D.C.; T.A., E.S.; S.H., L.B.; K.S., C.S.). Search terms were identified utilizing Medical Subject Headings (MeSH) and Emtree and included “glucocorticoids,” “rheumatoid arthritis,” “pneumonia,” and “respiratory tract infections,” Inclusion criteria included human subjects over the age of 18 with seropositive RA, on a combination of GC (prednisone, methylprednisolone, or prednisolone) with DMARD (methotrexate [MTX], hydroxychloroquine [HCQ], or sulfasalazine [SSZ]) and developed pneumonia of bacterial, viral, or fungal origin. The control groups were on a DMARD monotherapy regimen. Articles were excluded if they were not in English, had less than 20 participants, were case reports or literature reviews, included animal subjects, and did not adhere to the established PICO framework. Five teams of two researchers individually sorted through abstracts of articles based on the inclusion and exclusion criteria. The same teams individually sorted through full-text articles of selected abstracts based on the same criteria. Conflicts between each team were resolved by a separate researcher. Odds ratios were utilized to quantify the effect sizes of combined studies from a random effects model. Chi-square tests and I2 statistics were utilized to analyze heterogeneity.

Results: A total of 3360 articles were identified from all databases, and 416 duplicate articles were removed. Thus, a total of 2944 articles abstracts were screened, of which 2819 articles either did not meet the inclusion criteria or did meet the exclusion criteria. A total of 125 articles were retrieved and assessed for full-text eligibility, of which only three observational articles were included for meta-analysis. Statistical results revealed that patients treated with DMARDs monotherapy are 95% (95% CI: 0.65–0.99) less likely to develop pneumonia compared to patients treated with a DMARD and GCs (p=0.002).

Conclusions: Our data suggest that RA patients have a higher probability of developing pneumonia on combination therapy with GCs, compared to monotherapy with DMARDs. To our knowledge, our findings are the first to systematically review and statistically evaluate the relationship between the use of GCs and show an increased chance of developing pneumonia.

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