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A comprehensive review of rituximab therapy in rheumatoid arthritis patients

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Abstract

Rituximab (RTX) is an approved treatment for rheumatoid arthritis (RA) patients that do not respond adequately to disease-modifying antirheumatic drugs. However, different new concerns, such as efficacy, optimum dose, safety issues, prediction of response to RTX, and pregnancy outcomes have attracted a lot of attention. The PubMed database was systematically reviewed for the last published articles, new findings, and controversial issues regarding RTX therapy in RA using “Rheumatoid arthritis” AND “rituximab” keywords, last updated on June 18, 2019. From 1812 initial recorders, 162 studies met the criteria. Regarding the optimum dose, low-dose RTX therapy (2 × 500 mg) seems as effective as standard dose (2 × 1000 mg), safer, and more cost-effective. The most common reported safety challenges included de novo infections, false negative serologic tests of viral infections, reactivation of chronic infections, interfering with vaccination outcome, and development of de novo psoriasis. Other less reported side effects are infusion reactions, nervous system disorders, and gastrointestinal disorders. Lower exposure to other biologics, presence of some serological markers (e.g., anti-RF, anti-CCP, IL-33, ESR), specific variations in FCGR3A, FCGR2A, TGFβ1, IL6, IRF5, BAFF genes, and also EBV-positivity could be used to predict response to RTX. Although there is no evidence of the teratogenic effect of RTX, it is recommended that women do not expose themselves to RTX at least 6 months before the conception. Only a reversible reduction of B cell-count in the offspring may be the pregnancy-related outcome. Although RTX is an effective therapeutic option for RA, more studies on optimum doses, prevention of RTX-related side effects, prediction of RTX response, and safety during the pregnancy are required.

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Authors and Affiliations

  1. Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Soheil Tavakolpour

  2. Rheumatology and Internal Medicine, Rheumatology Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Soheil Tavakolpour, Samira Alesaeidi & Mojtaba GhasemiAdl

  3. Infectious Diseases and Tropical Medicine Research Center (IDTMRC), department of aerospace and subaquatic medicine, AJA University of Medical Sciences, Tehran, Iran

    Mohammad Darvishi

  4. School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Sahar Darabi-Monadi

  5. Pars Advanced and Minimally Invasive Medical Manners Research Center, Pars Hospital, Iran University of Medical Sciences, Tehran, Iran

    Meisam Akhlaghdoust

  6. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Somayeh Elikaei Behjati

  7. Amir’Alam Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Arash Jafarieh

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  1. Soheil Tavakolpour
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  2. Samira Alesaeidi
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  3. Mohammad Darvishi
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  4. Mojtaba GhasemiAdl
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  5. Sahar Darabi-Monadi
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  6. Meisam Akhlaghdoust
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  8. Arash Jafarieh
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Contributions

Soheil Tavakolpour and Samira Alesaeidi contributed substantially to the study conception and design; Mojtaba Ghasemiadl, Sahar Darabi Monadi, Somayeh Elkaei Behjati, and Meisam Akhlaghdoust contributed to the literature review, acquisition and analysis of data; Soheil Tavakolpour drafted the manuscript; Samira Alesaeidi, Mohammad Darvishi, and Arash Jafarieh contributed to the revision of the manuscript. All authors approved the final version and agree to be accountable for all aspects of the work.

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Correspondence to Soheil Tavakolpour.

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Tavakolpour, S., Alesaeidi, S., Darvishi, M. et al. A comprehensive review of rituximab therapy in rheumatoid arthritis patients. Clin Rheumatol 38, 2977–2994 (2019). https://doi.org/10.1007/s10067-019-04699-8

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