{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:14:12Z","timestamp":1791828852972,"version":"4.3.4"},"reference-count":106,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The management of rheumatoid arthritis (RA) has advanced significantly with the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs). Despite these therapeutic strides, RA prognosis remains profoundly affected by comorbid conditions, particularly cardiovascular and metabolic complications, which increase both morbidity and mortality. The role of bDMARDs in modulating comorbidities remains underexplored, with limited evidence on their effects across various non-RA conditions, such as respiratory, diabetic, and hematologic disorders. This systematic review aimed to evaluate the impact of bDMARDs on the progression and outcomes of comorbidities in RA patients, providing insights to guide personalized treatment approaches. Methods: This systematic review was registered in PROSPERO (CRD42022345903) and followed the PRISMA guidelines. Original research articles from PubMed and Scopus, published up to 18 July 2024, were included. Studies assessing the impact of bDMARDs on comorbidities in RA patients met the eligibility criteria. Results: A total of thirteen studies met the inclusion criteria. They were published from inception until July 2024. The studied comorbidities included pulmonary conditions (asthma, chronic obstructive pulmonary disease, and interstitial lung disease) (n = 2); diabetes (n = 3); anemia (n = 3); and malignancies (n = 3). The bDMARDs studied were tumor necrosis factor inhibitors (TNFis) (n = 9); Rituximab (n = 5); Tocilizumab (n = 5); Abatacept (n = 5); and Anakinra (n = 2). The most reported effects of bDMARDs on comorbidities were the following: (i) an exacerbation of pulmonary comorbidities for Abatacept and TNFis; (ii) patients switched to or initiated on Abatacept as their first targeted disease-modifying antirheumatic drug (tDMARD) showed directionally lower rates and costs of T2DM-related complications compared with patients switching to or initiating other tDMARDs; (iii) there was no difference between Abatacept and TNFis or Rituximab\/Tocilizumab regarding diabetes treatment switching or intensification; (iv) Anakinra significantly reduced the HbA1c%; (v) decreased serum hepcidin levels and improvement in anemia were observed in patients treated with TNFis or Tocilizumab; and (vi) no decrease in overall survival time or the significant incident malignancy rate was noted in RA patients. Conclusions: Overall, bDMARDs appear safe for use in RA patients with comorbidities and may even provide specific benefits for conditions such as anemia and diabetes. These findings suggest that clinicians could consider tailoring biologic therapy based on each patient\u2019s comorbidity profile, potentially enhancing both RA management and comorbidity outcomes. For instance, selecting biologics such as Anakinra or Tocilizumab might be advantageous for RA patients with concurrent diabetes or anemia, given their observed metabolic and hematologic benefits. This personalized approach could improve the quality of life and reduce healthcare costs by addressing RA and associated comorbidities more effectively.<\/jats:p>","DOI":"10.3390\/jcm14134547","type":"journal-article","created":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T03:33:25Z","timestamp":1750995205000},"page":"4547","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impact of Biologic Drugs on Comorbidity Outcomes in Rheumatoid Arthritis: A Systematic Review"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9185-1710","authenticated-orcid":false,"given":"Soumaya","family":"Boussaid","sequence":"first","affiliation":[{"name":"Rheumatology Department, Rabta Hospital, Tunis 1007, Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Research Unit LR 05 SP 01, La Rabta Hospital, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7297-0837","authenticated-orcid":false,"given":"Rim","family":"Dhahri","sequence":"additional","affiliation":[{"name":"Faculty of Medicine of Tunis, University Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Rheumatology Department, Military Hospital of Tunis, Tunis 1006, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7955-8653","authenticated-orcid":false,"given":"Safa","family":"Rahmouni","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Rabta Hospital, Tunis 1007, Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Research Unit LR 05 SP 01, La Rabta Hospital, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1133-5511","authenticated-orcid":false,"given":"Halil \u0130brahim","family":"Ceylan","sequence":"additional","affiliation":[{"name":"Department of Physical Education of Sports Teaching, Faculty of Sports Sciences, Atat\u00fcrk University, 25240 Erzurum, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa","family":"Hassayoun","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Rabta Hospital, Tunis 1007, Tunisia"},{"name":"Research Unit LR 05 SP 01, La Rabta Hospital, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1698-517X","authenticated-orcid":false,"given":"Maissa","family":"Abbes","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Rabta Hospital, Tunis 1007, Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Research Unit LR 05 SP 01, La Rabta Hospital, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khaoula","family":"Zouaoui","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Rabta Hospital, Tunis 1007, Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Research Unit LR 05 SP 01, La Rabta Hospital, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8091-1856","authenticated-orcid":false,"given":"Ismail","family":"Dergaa","sequence":"additional","affiliation":[{"name":"Higher Institute of Sports and Physical Education of Ksar Said, University of Manouba, Manouba 2010, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Rekik","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Rabta Hospital, Tunis 1007, Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Research Unit LR 05 SP 01, La Rabta Hospital, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Boussaid","sequence":"additional","affiliation":[{"name":"English Department, College of arts and humanities of Sousse, University of Sousse, Sousse 4002, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imen","family":"Gharsallah","sequence":"additional","affiliation":[{"name":"Faculty of Medicine of Tunis, University Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Rheumatology Department, Military Hospital of Tunis, Tunis 1006, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4615-6687","authenticated-orcid":false,"given":"Raul Ioan","family":"Muntean","sequence":"additional","affiliation":[{"name":"Department of Physical Education and Sport, Faculty of Law and Social Sciences, University \u201c1 Decembrie 1918\u201d of Alba Iulia, 510009 Alba Iulia, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hela","family":"Sahli","sequence":"additional","affiliation":[{"name":"Rheumatology Department, Rabta Hospital, Tunis 1007, Tunisia"},{"name":"Faculty of Medicine of Tunis, University Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Research Unit LR 05 SP 01, La Rabta Hospital, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2147\/JMDH.S393061","article-title":"Assessment Tools for Pulmonary Involvement in Patients with Ankylosing Spondylitis: Is Diaphragmatic Ultrasonography Correlated to Spirometry?","volume":"16","author":"Dhahri","year":"2023","journal-title":"J. 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