Received: 24 September 2018 | Accepted: 14 November 2018 DOI: 10.1002/jcp.27860 REVIEW ARTICLE Strategies toward rheumatoid arthritis therapy; the old and the new Mojtaba Abbasi 1 | Mohammad Javad Mousavi 2,3,9 | Sirous Jamalzehi 4 | Reza Alimohammadi 5 | Maryam Hasanzadeh Bezvan 6,10 | Hamed Mohammadi 7,8 | Saeed Aslani 3 1 Department of Veterinary Medicine, Faculty of Veterinary Medicine, Islamic Azad University, Shahr‐e Kord, Iran 2 Department of Immunology and Allergy, Faculty of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran 3 Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran 4 Department of Medical Laboratory Sciences, Iranshahr University of Medical Sciences, Iranshahr, Iran 5 Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 6 Department of Microbiology, Islamic Azad University, Tehran, Iran 7 Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 8 Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran 9 Veterinary Medicine, Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran 10 Department of Microbiology, Shahr‐e‐Qods Branch, Islamic Azad University, Tehran, Iran Correspondence Mohammad Javad Mousavi and Saeed Aslani, Ph.D, Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Poursina St., Tehran 14179‐13119, Iran. Email: sm-mousavi@razi.tums.ac.ir (M.J.M.); s-aslani@razi.tums.ac.ir (S.A.) Abstract Currently, medications used to treat rheumatoid arthritis (RA) are glucocorticoids (GCs) and nonsteroidal anti‐inflammatory drugs (NSAIDs), predominantly used for controlling the pain and inflammation, disease‐modifying antirheumatic drugs (DMARDs), administered as first‐line medication for newly diagnosed RA cases, and biological therapies, used to target and inhibit specific molecules of the immune and inflammatory responses. NSAIDs and other GCs are effective in alleviating the pain, inflammation, and stiffness due to RA. DMARDs that are used for RA therapy are hydroxychloroquine, methotrexate, leflunomide, and sulfasalazine. The biological therapies, on the contrary, are chimeric anti‐CD20 monoclonal antibody, rituximab, inhibitors of tumor necrosis factor‐α (TNF‐α) like etanercept, infliximab, and adalimumab, a recombinant inhibitor of interleukin‐1 (IL‐1), anakinra, and costimula- tion blocker, abatacept. Moreover, newly under evaluation biological therapies include new TNF‐α inhibitors, JAK inhibitors, anti‐interleukin‐6‐receptor monoclonal antibodies (mABs), and antibodies against vital molecules involved in the survival and development of functional B cells. The new strategies to treat RA has improved the course of the disease and most of the patients are successful in remission of the clinical manifestations if the diagnosis of the disease occur early. The probability of remission increase if the diagnosis happens rapidly and treat‐to‐target approach are implemented. In this review article, we have attempted to go through the treatment strategies for RA therapy both the routine ones and those which have been developed over the past few years and currently under investigation. KEYWORDS biological agents, disease‐modifying antirheumatic drugs, glucocorticoids, monoclonal antibody, nonsteroidal anti‐inflammatory drugs, rheumatoid arthritis 1 | INTRODUCTION Rheumatoid arthritis (RA) is known as an inflammatory, chronic disease of joint with autoimmune basis and is mainly characterized by autoantibodies against immunoglobulin G (which is called rheumatoid factor [RF]) and anticitrullinated protein antibodies. In cases of incomplete treatment implementations, RA can result in joint harms and disability. The disease in heterogeneous and various clinical images and pathogenic pathways are seen (Almasi et al., 2016; Anaraki Mohammadi et al., 2018; Mahmoudi, Aslani, Fadaei, & J Cell Physiol. 2018;1-14. wileyonlinelibrary.com/journal/jcp © 2018 Wiley Periodicals, Inc. | 1