Review

Authors: Andrei-Flavius Radu, Simona Gabriela Bungau

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease of unknown etiology, primarily affecting the joints, then extra-articular manifestations can occur. Due to its complexity, which is based on an incompletely elucidated pathophysiological mechanism, good RA management requires a multidisciplinary approach. The clinical status of RA patients has improved in recent years due to medical advances in diagnosis and treatment, that have made it possible to reduce disease activity and prevent systemic complications. The most promising results were obtained by developing disease-modifying anti-rheumatic drugs (DMARDs), the class to which conventional synthetic, biologic, and targeted synthetic drugs belong. Furthermore, ongoing drug development has led to obtaining molecules with improved efficacy and safety profiles, but further research is needed until RA turns into a curable pathology. In the present work, we offer a comprehensive perspective on the management of RA, by centralizing the existing data provided by significant literature, emphasizing the importance of an early and accurate diagnosis associated with optimal personalized treatment in order to achieve better outcomes for RA patients. In addition, this study suggests future research perspectives in the treatment of RA that could lead to higher efficacy and safety profiles and lower financial costs.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Models, Biological; Protein Kinase Inhibitors

PubMed: 34831081
DOI: 10.3390/cells10112857

Review

Authors: B N Cronstein

Because of methotrexate's well-documented efficacy in the treatment of rheumatoid arthritis, it is important that we understand the mechanism of action of this drug. There are two biochemical mechanisms by which methotrexate may modulate inflammation: (1) promotion of adenosine release and (2) inhibition of transmethylation reactions. Evidence is reviewed that favors the notion that the endogenous anti-inflammatory autocoid adenosine mediates the anti-inflammatory effects of methotrexate. This insight should aid in the design of new agents for the treatment of rheumatoid arthritis and other inflammatory diseases.

Topics: Adenosine; Animals; Anti-Inflammatory Agents; Antirheumatic Agents; Arthritis, Rheumatoid; Enzyme Inhibitors; Folic Acid Antagonists; Humans; Methotrexate; Methylation

PubMed: 9361153
DOI: 10.1016/s0889-857x(05)70358-6

Review

Authors: Zixuan Zhao, Zhenglai Hua, Xinyi Luo...

Methotrexate (MTX) has been used for the treatment of rheumatoid arthritis (RA) for about forty years and to date MTX remains the part of global standard of treatment for RA. The efficacy of MTX in RA is the result of multiple mechanisms of action. In order to summarize the possible pharmacological mechanisms of MTX in the treatment of RA, this review will elaborate on folate antagonism, promotion of adenosine accumulation, regulation of inflammatory signaling pathways, bone protection and maintenance of immune system function.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Methotrexate

PubMed: 35658215
DOI: 10.1016/j.biopha.2022.113074

Review

Authors: Pan Shen, Weiji Lin, Xuan Deng...

Autoimmune diseases are a worldwide health problem with growing rates of morbidity, and are characterized by breakdown and dysregulation of the immune system. Although their etiology and pathogenesis remain unclear, the application of dietary supplements is gradually increasing in patients with autoimmune diseases, mainly due to their positive effects, relatively safety, and low cost. Quercetin is a natural flavonoid that is widely present in fruits, herbs, and vegetables. It has been shown to have a wide range of beneficial effects and biological activities, including anti-inflammation, anti-oxidation, and neuroprotection. In several recent studies quercetin has reportedly attenuated rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and systemic lupus erythematosus in humans or animal models. This review summarizes the evidence for the pharmacological application of quercetin for autoimmune diseases, which supports the view that quercetin may be useful for their prevention and treatment.

Topics: Animals; Anti-Inflammatory Agents; Antirheumatic Agents; Autoimmune Diseases; Humans; Quercetin

PubMed: 34248976
DOI: 10.3389/fimmu.2021.689044

Meta-Analysis Review

Authors: Silvia Minozzi, Stefanos Bonovas, Theodore Lytras...

Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection). We searched Medline, Embase, and the Cochrane Library up to May 2014 to identify eligible studies in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis that evaluated anti-TNF drugs compared with placebo or no treatment. Expert opinion: Our study encompassed data from 71 randomized controlled trials involving 22,760 participants (range of follow-up: 1-36 months) and seven open label extension studies with 2,236 participants (range of follow-up: 6-48 months). Quantitative synthesis of the available data found statistically significant increases in the occurrence of any infections (20%), serious infections (40%), and tuberculosis (250%) associated with anti-TNF drug use, while the data for opportunistic infections were scarce. The quality of synthesized evidence was judged as moderate. Further evidence from registries and long-term epidemiological studies are needed to better define the relationship between anti-TNF agents and infection complications.

Topics: Adult; Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Humans; Infections; Randomized Controlled Trials as Topic; Spondylitis, Ankylosing; Tumor Necrosis Factor-alpha

PubMed: 27924643
DOI: 10.1080/14740338.2016.1240783

Review

Authors: Hideto Kameda, Shigeto Kobayashi, Naoto Tamura...

Non-radiographic axial spondyloarthritis (nr-axSpA) is a subgroup of axial spondyloarthritis (axSpA) without fulfilling the modified New York criteria of sacroiliac joint radiographs for ankylosing spondylitis (AS). AS and nr-axSpA share various demographic and clinical features and disease burden, although sex and objective inflammatory findings such as elevated serum C-reactive protein level are slightly different between AS and nr-axSpA. Recently, diagnostic guidance for nr-axSpA in Japan was proposed for epidemiological studies of a population with a low prevalence of HLA-B27 positivity and the use of molecular targeted agents suitable for the unique medical care system in Japan. A biological agent targeting interleukin-17 was approved for nr-axSpA by the Pharmaceutical and Medical Devices Agency (PMDA) in August 2020. Some other biological agents will be also available for Japanese patients with nr-axSpA in the near future.

Topics: Antirheumatic Agents; Biomarkers; Clinical Trials as Topic; Humans; Spondylarthritis

PubMed: 32996809
DOI: 10.1080/14397595.2020.1830512

Authors: Linda Rüegg, Andrea Pluma, Sabrina Hamroun...

OBJECTIVES

To update the existing European Alliance of Associations for Rheumatology (EULAR) points to consider (PtC) for use of antirheumatic drugs in reproduction, pregnancy, and lactation, including additional drugs and adverse outcomes as well as paternal drug safety.

METHODS

According to the EULAR standardised operating procedures, an international task force (TF) defined the questions for a systematic literature review, followed by formulation of the updated statements. A predefined voting process was applied to each overarching principle and statement. Level of evidence and strength of recommendation were assigned, and participants finally provided their level of agreement for each item.

RESULTS

The TF proposes 5 overarching principles and 12 recommendations for the use of antirheumatic drugs before and during pregnancy, through lactation, and in male patients. The current evidence indicates that synthetic disease-modifying antirheumatic drugs (DMARDs) compatible with pregnancy include antimalarials, azathioprine, colchicine, cyclosporine, sulfasalazine, and tacrolimus. Regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, a more restrictive approach to their use during pregnancy is recommended. Based on an individualised risk-benefit assessment, all tumour necrosis factor inhibitor (TNFi) biologic DMARDs (bDMARDs) can be used throughout pregnancy, and non-TNFi bDMARDs may be used if needed. In relation to lactation, compatible drugs include antimalarials, azathioprine, colchicine, cyclosporine, glucocorticoids, intravenous immunoglobulin (IVIG), NSAIDs, sulfasalazine, and tacrolimus. All bDMARDs are considered compatible with breastfeeding. Concerning the use of drugs in men, compatible options include antimalarials, azathioprine, colchicine, cyclosporine, IVIG, leflunomide, methotrexate, mycophenolate, NSAIDs, glucocorticoids, sildenafil, sulfasalazine, tacrolimus, and bDMARDs.

CONCLUSIONS

The updated recommendations provide consensus guidance and will help to improve the quality of care of patients during the phases of reproduction, pregnancy, and lactation.

Topics: Female; Humans; Male; Pregnancy; Antirheumatic Agents; Breast Feeding; Lactation; Pregnancy Complications; Reproduction; Rheumatic Diseases; Systematic Reviews as Topic

PubMed: 40287311
DOI: 10.1016/j.ard.2025.02.023

Review

Authors: Qin-Yi Su, Jing Luo, Yan Zhang...

BACKGROUND

Difficult-to-treat Rheumatoid arthritis (D2T RA) is primarily characterised by failure of at least two different mechanism of action biologic/targeted synthetic disease-modifying antirheumatic drug (DMARDs) with evidence of active/progressive disease. While a variety of drugs have been used in previous studies to treat D2T RA, there has been no systematic summary of these drugs. This study conducted a systematic review of randomized controlled trials aimed at analyzing the efficacy and safety of individual therapeutic agents for the treatment of D2T RA and recommending the optimal therapeutic dose.

METHODS

The English databases were searched for studies on the treatment of D2T RA published between the date of the database's establishment and March, 2024. This study uses R 3.1.2 for data analysis, and the rjags package runs JAGS 3.4.0.20. The study fitted a stochastic effects Bayesian network meta-analysis for each outcome measure.

RESULT

A total of 42 studies were included in this study. Compared with placebo, the improvement of Disease Activity Score of 28 Joints (DAS28) score is ranked from high to low as tocilizumab, baricitinib and opinercept. The improvement of American College of Rheumatology 50 response (ACR50) score in patients with drug use was ranked from good to poor as follows: olokizumab, tocilizumab, adalimumab, baricitinib, and upadacitinib, and 8 mg/4w tocilizumab demonstrated the best efficacy. Notably, rituximab is generally the safest drug. Janus kinase (JAK) inhibitors and T cell costimulation modulators are effective in D2T RA refractory to biologic DMARDs, while JAK inhibitors and interleukin-6 (IL-6) inhibitors show effectiveness in D2T RA refractory to csDMARDs.

CONCLUSION

Tocilizumab and rituximab have better efficacy and safety in the treatment of D2T RA, and the 8 mg/4w dose of tocilizumab may be the first choice for achieving disease remission.

Topics: Humans; Antirheumatic Agents; Arthritis, Rheumatoid; Randomized Controlled Trials as Topic; Treatment Outcome

PubMed: 39198829
DOI: 10.1186/s12967-024-05569-x

Review

Authors: Tue Wenzel Kragstrup, Kristine Jagd Ottosen, Line Uhrenholt...

This review presents a simplified model to understand better how disease-modifying anti-inflammatory drugs (DMAIDs) work in immune-mediated inflammatory diseases (IMIDs) with a focus on rheumatology, dermatology, and gastroenterology. In this model, IMIDs are listed on a spectrum from autoinflammatory to autoimmune characterised by the involvement of either mostly the innate or the adaptive immune system. DMAIDs specifically target these immune components and have shown efficacy in distinct IMIDs. DMAID classes include TNF blockers, IL-1 blockers, IL-6 receptor blockers, IL-17 blockers, IL-23 blockers, and janus kinase inhibitors.

Topics: Humans; Autoimmune Diseases; Anti-Inflammatory Agents; Antirheumatic Agents; Inflammation

PubMed: 39221881
DOI: 10.61409/V12230795

Review

Authors: D Aletaha, A Kerschbaumer

Therapy reduction in rheumatoid arthritis (RA) is still a challenge for physicians as well as for patients. Effective therapy with subsequent achievement of low disease activity or even remission is achievable for numerous patients using currently available treatment options. Therapy discontinuation has therefore become a hot topic and the risk of exacerbation of well-controlled RA must be weighed against the medical and economic benefits of reducing or even discontinuing therapy. This article gives a review of data regarding tapering of therapy in RA, focusing on conventional disease-modifying antirheumatic drug (DMARD) monotherapy, reduction of conventional therapy under continuing therapy with biologics and discontinuation of biologics. Important influencing factors for a safe and successful tapering procedure appear to be disease activity, disease duration and the tapering process itself (i.e. gradual dose reduction vs. abrupt discontinuation). Additionally, the so-called nocebo effect should also be taken into consideration for interpretation of drug tapering studies.

Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Monitoring; Evidence-Based Medicine; Humans; Immunosuppressive Agents; Treatment Outcome

PubMed: 28058499
DOI: 10.1007/s00393-016-0251-7