Lakhasly

Review Anti-rheumatoid drugs advancements: New insights into the molecular treatment of rheumatoid arthritis Reda Ben Mrid, Najat Bouchmaa, Hassan Ainani, Rachid El Fatimy, Gabriel Malka, Loubna Mazini * Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco ARTICLE INFO Keywords: Rheumatoid arthritis Conventional drugs RNA therapy Phosphate-based treatments Cannabinoid-based drugs ABSTRACT Rheumatoid arthritis (RA) is one of more than 100 types of arthritis.Under normal conditions, the synovial mem- brane is almost acellular, consisting of a thin layer of cells composed mainly of macrophage and fibroblast-derived cells [2], while it displays an inflammatory phenotype and becomes more hypertrophic in patients with RA [3].These consist of the activation and infiltration into the synovial tissue of different immune cells, mainly macrophages, T cells and dendritic cells (DCs), in addition to B cells, neutrophils and mast cells, which are all involved in the production of different chemical mediators and (interleukins) ILs, making the tissue inflammatory [4].Indeed, non-steroidal anti-inflammatory drugs (NSAIDS) and corticosteroids are a widely used category of molecules reported to be very efficient for alleviating pain and stiffness in RA pa- tients, without moderating the disease progression.Contents lists available at ScienceDirect Biomedicine & Pharmacotherapy journal homepage: www.elsevier.com/locate/biopha https://doi.org/10.1016/j.biopha.2022.113126 Received 4 April 2022; Received in revised form 13 May 2022; Accepted 13 May 2Non-steroidal anti- inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs) remain the most known treatments used against RA. However, not all patients respond well to these drugs and therefore, new solutions are of immense need to improve the disease outcomes.Even worse, if RA is poorly controlled, other pathological manifestations may be developed, including peri- carditis/pleuritis, keratitis, small vessel vasculitis, and pulmonary granulomas [2].The disease- modifying antirheumatic drugs (DMARDs), are another class of mole- cules used for the management of inflammation including conventional synthetic DMARDs, targeted synthetic DMARDs (tsDMARDs), and bio- logical DMARDs (bDMARDs).However, efforts are nowadays devoted in order to develop new DMARDs with low

• Corresponding author.1.

Review
Anti-rheumatoid drugs advancements: New insights into the molecular
treatment of rheumatoid arthritis
Reda Ben Mrid, Najat Bouchmaa, Hassan Ainani, Rachid El Fatimy, Gabriel Malka,
Loubna Mazini *
Institute of Biological Sciences (ISSB-P), Mohammed VI Polytechnic University (UM6P), 43150 Ben-Guerir, Morocco
ARTICLE INFO
Keywords:
Rheumatoid arthritis
Conventional drugs
RNA therapy
Phosphate-based treatments
Cannabinoid-based drugs
ABSTRACT
Rheumatoid arthritis (RA) is one of more than 100 types of arthritis. This chronic autoimmune disorder affects
the lining of synovial joints in about 0.5% of people and may induce severe joints deformity and disability. RA
impacts health life of people from all sexes and ages with more prevalence in elderly and women people. Sig-
nificant improvement has been noted in the last two decades revealing the mechanisms of the development of
RA, the improvement of the early diagnosis and the development of new treatment options. Non-steroidal anti-
inflammatory drugs (NSAIDs), corticosteroids, and disease-modifying antirheumatic drugs (DMARDs) remain the
most known treatments used against RA. However, not all patients respond well to these drugs and therefore,
new solutions are of immense need to improve the disease outcomes. In the present review, we discuss and
highlight the recent findings concerning the different classes of RA therapies including the conventional and
modern drug therapies, as well as the recent emerging options including the phyto-cannabinoid and cell- and
RNA-based therapies. A better understanding of their mechanisms and pathways might help find a specific target
against inflammation, cartilage damage, and reduce side effects in arthritis.

1. Introduction
   For any disease, the development of an efficient treatment strategy
   requires a well understanding of its etiology and its molecular mecha-
   nism. For rheumatoid arthritis (RA), the real causes and mechanisms
   leading to the establishment and the development of the disease are not
   well understood [1]. However, it is recognized that this pathology is
   featured by a chronic autoimmune disorder that impacts particularly the
   lining of synovial joints. Under normal conditions, the synovial mem-
   brane is almost acellular, consisting of a thin layer of cells composed
   mainly of macrophage and fibroblast-derived cells [2], while it displays
   an inflammatory phenotype and becomes more hypertrophic in patients
   with RA [3]. These consist of the activation and infiltration into the
   synovial tissue of different immune cells, mainly macrophages, T cells
   and dendritic cells (DCs), in addition to B cells, neutrophils and mast
   cells, which are all involved in the production of different chemical
   mediators and (interleukins) ILs, making the tissue inflammatory [4].
   Early diagnosis might be crucial for averting or slowing the pro-
   gression of joint damage. Once RA pathology is confirmed, rapid med-
   ical care is required to either reduce the disease activity or even reach
   full remission. Otherwise, patients may develop joint damages and
   disability. Recently, it has been reported that around 40% of RA patients
   who are not well treated are unable to work within 10 years of the onset
   of the disease [5,6]. Even worse, if RA is poorly controlled, other
   pathological manifestations may be developed, including peri-
   carditis/pleuritis, keratitis, small vessel vasculitis, and pulmonary
   granulomas [2].
   At the other side, different approaches have been developed to
   alleviate the impacts or treat RA. Most of them are anti-inflammatory
   related treatments. Indeed, non-steroidal anti-inflammatory drugs
   (NSAIDS) and corticosteroids are a widely used category of molecules
   reported to be very efficient for alleviating pain and stiffness in RA pa-
   tients, without moderating the disease progression. The disease-
   modifying antirheumatic drugs (DMARDs), are another class of mole-
   cules used for the management of inflammation including conventional
   synthetic DMARDs, targeted synthetic DMARDs (tsDMARDs), and bio-
   logical DMARDs (bDMARDs). These molecules have proven their
   effectiveness on alleviating the disease severity and thus present the
   advantage of averting or delaying the joint deformity [7]. However,
   efforts are nowadays devoted in order to develop new DMARDs with low

• Corresponding author.
  E-mail address: [email protected] (L. Mazini).
  Contents lists available at ScienceDirect
  Biomedicine & Pharmacotherapy
  journal homepage: www.elsevier.com/locate/biopha
  https://doi.org/10.1016/j.biopha.2022.113126
  Received 4 April 2022; Received in revised form 13 May 2022; Accepted 13 May 2