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Rheumatoid Arthritis: Current Status and Future Challenges

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (24 September 2024) | Viewed by 12400

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Special Issue Editor

Dr. Blanca Hernández-Cruz

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Guest Editor

Rheumatology Department, Virgen Macarena University Hospital, Dr Fedriani Avenue No 3, 41009 Seville, Spain
Interests: rheumatology; rheumatic diseases; clinical rheumatology; rheumatoid arthritis

Special Issue Information

Dear Colleagues,

In the last 25 years, we have witnessed changes in the approach to Rheumatoid Arthritis. The main changes have occurred in the knowledge of the pathogenesis, new classification criteria, improved autoantibodies of diagnostic, implementation of the treat-to-target strategy, more and better drugs and ways to use them, and the identification and management of associated comorbidities. Above all, we have seen the teamwork of physicians and health professionals, the pharmaceutical industry, and regulatory agencies. All of this focuses on the patient with shared decisions with them and involving their associations. All these milestones have made it possible to modify the clinical course and prognosis of the disease.

This Special Issue aims to update the clinician about these milestones with some original articles and reviews, and also discuss different hot topics.

It is a pleasure for me, on behalf of the editorial committee of the Journal of Clinical Medicine, to invite you to contribute with state-of-the-art reviews as well as original research. All of them will be considered for inclusion. The scope will be advances in old and new drugs, old and new treatment strategies, treatment of pain and depression, management of RA-related comorbidities, how to include the patient perspective in the daily practice, unmet needs, the remission concept, management of comorbidities, how to improve outcomes in the daily practice, etc.

I hope you are interested in submitting your work in this Special Issue. I look forward to hearing from you.

Dr. Blanca Hernández-Cruz
Guest Editor

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Keywords

rheumatoid arthritis
treat to target
difficult to treat rheumatoid arthritis
unmet needs
patient reported outcomes
pathogenesis
classification criteria
treatment recommendations
outcomes

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Published Papers (9 papers)

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Editorial

Jump to: Research, Review

6 pages, 204 KiB

Open AccessEditorial

The So-Called Pre-Clinical Rheumatoid Arthritis: Doubts, Challenges, and Opportunities

by Raimon Sanmartí, Beatriz Frade-Sosa and Andres Ponce

J. Clin. Med. 2024, 13(21), 6387; https://doi.org/10.3390/jcm13216387 - 25 Oct 2024

Viewed by 325

Abstract

A Clinical Case of Possible Pre-Rheumatoid Arthritis [...] Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Status and Future Challenges)

Research

Jump to: Editorial, Review

12 pages, 855 KiB

Open AccessArticle

Incidence Rates of Infections in Rheumatoid Arthritis Patients Treated with Janus Kinase or Interleukin-6 Inhibitors: Results of a Retrospective, Multicenter Cohort Study

by Shuhei Yoshida, Masayuki Miyata, Eiji Suzuki, Takashi Kanno, Yuya Sumichika, Kenji Saito, Haruki Matsumoto, Jumpei Temmoku, Yuya Fujita, Naoki Matsuoka, Tomoyuki Asano, Shuzo Sato and Kiyoshi Migita

J. Clin. Med. 2024, 13(10), 3000; https://doi.org/10.3390/jcm13103000 - 20 May 2024

Viewed by 1109

Abstract

Objective: This study aimed to compare the incidence rates (IRs) of infections, including herpes zoster (HZ), in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) or interleukin-6 inhibitors (IL-6is). Methods: We retrospectively analyzed 444 RA patients treated using IL-6is (n = 283) or JAKis (n = 161). After adjusting for clinical characteristic imbalances by propensity score matching (PSM), we compared the IRs of infections including HZ between the JAKi and IL-6i groups. Results: Observational period: 1423.93 patient years (PY); median observational period: 2.51 years. After PSM, incidence rate ratios comparing JAKi with IL-6i were 3.45 (95% confidence interval [CI]: 1.48–9.04) for serious infections other than HZ indicating that the JAKi-treated group was more likely to develop serious infection than the IL-6i-treated group. Multivariate Cox regression analyses revealed that the use of prednisolone > 5.0 mg/day, coexisting interstitial lung disease (ILD), and diabetes mellitus (DM) were independent risk factors for serious infections. The crude IR for HZ was significantly higher in the JAKi group, but the difference between groups was not significant (IRR: 2.83, 95% CI: 0.87–10.96) in PSM analysis. Unadjusted and PSM analyses performed in our study showed increased IRs of serious infections in patients with RA treated with JAKis compared with those treated with IL-6is. Conclusions: The presence of ILD or DM and the use of prednisolone were found to be independent risk factors for serious infection in RA patients treated using JAKis. Whereas the IRs for HZ after PSM were not significantly different between the JAKi and IL-6i groups. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Status and Future Challenges)

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15 pages, 2097 KiB

Open AccessFeature PaperArticle

The Real-World Effectiveness, Persistence, Adherence, and Safety of Janus Kinase Inhibitor Baricitinib in Rheumatoid Arthritis: A Long-Term Study

by Alberto Calvo-Garcia, Esther Ramírez Herráiz, Irene María Llorente Cubas, Blanca Varas De Dios, Juana Benedí González, Alberto Morell Baladrón and Rosario García-Vicuña

J. Clin. Med. 2024, 13(9), 2517; https://doi.org/10.3390/jcm13092517 - 25 Apr 2024

Cited by 1 | Viewed by 1368

Abstract

Background/Aim: Baricitinib (BAR) is the first oral selective Janus kinase inhibitor approved in Europe for rheumatoid arthritis (RA). Real-world data are still needed to clarify its long-term benefits/risk profile. This study aimed to evaluate the effectiveness, persistence, adherence, and safety of BAR in a real-world setting. Methods: An ambispective study was conducted between October 2017 and December 2021 in RA patients starting BAR. The effectiveness was evaluated, assessing changes from the baseline of the Disease Activity Score using 28-joint counts-C reactive protein (DAS28CRP), and the achievement of low disease activity/remission. Drug persistence was evaluated using Kaplan–Meier analysis. Adherence was estimated using the medication possession ratio (MPR) and the 5-item Compliance Questionnaire for Rheumatology. Safety was assessed determining global incidence proportion and adverse event adjusted incidence rates. Results: In total, 61/64 recruited patients were finally analyzed, 83.6% were female, 78.7% were seropositive, the mean age was 58.1 (15.4) years, and the disease duration was 13.9 (8.3) years. A total of 32.8% of patients were naïve to biologics and 16.4% received BAR as monotherapy. The median exposure to BAR was 12.4 (6.6–31.2) months (range 3.1–51.4). A significant change in DAS28CRP was observed after treatment (difference −1.2, p = 0.000). 70.5% and 60.7% of patients achieved low disease activity or remission, respectively, and 50.8% (31/61) remained on BAR throughout the follow-up, with a median persistence of 31.2 (9.3–53.1) months. The average MPR was 0.96 (0.08) and all patients exhibited “good adherence” according to the questionnaire. In total, 21.3% of patients discontinued baricitinib due to toxicity. Conclusions: In our real-world practice, BAR demonstrated effectiveness, large persistence, high adherence to treatment, and an acceptable safety profile. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Status and Future Challenges)

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9 pages, 779 KiB

Open AccessArticle

Are There Sex-Related Differences in the Effectiveness of Janus Kinase Inhibitors in Rheumatoid Arthritis Patients?

by Cristina Martinez-Molina, Anna Feliu, Hye S. Park, Ana Juanes, Cesar Diaz-Torne, Silvia Vidal and Hèctor Corominas

J. Clin. Med. 2024, 13(8), 2355; https://doi.org/10.3390/jcm13082355 - 18 Apr 2024

Cited by 1 | Viewed by 1624

Abstract

Background: There is evidence suggesting the existence of sex differences in the effectiveness of specific drug classes for rheumatoid arthritis (RA). Our study stands as the first to elucidate sex-related differences in the effectiveness of Janus kinase (JAK) inhibitors. Methods: The study involved 150 RA patients treated with tofacitinib, baricitinib, upadacitinib, or filgotinib between September 2017 and October 2023. Sex differences in achieving remission and low disease activity (LDA) were identified through logistic regression analyses. Sex disparities in treatment effectiveness survival were evaluated through the Kaplan–Meier estimate, employing the log-rank test for comparison. The Cox model was applied to analyze the variable sex as a potential factor that could influence the maintenance of the JAK inhibitor treatment effectiveness. Results: Concerning the achievement of remission and LDA, no differences were observed between sexes in terms of the 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). With respect to the DAS28-erythrocyte sedimentation rate (ESR), female patients, compared to males, possessed 70% lower odds of achieving remission (p = 0.018) and 66% lower odds of achieving LDA (p = 0.023). No differences were observed in treatment effectiveness survival between sexes (p = 0.703). Sex was not found to influence the survival of JAK inhibitor treatment effectiveness (p = 0.704). Conclusions: Being a female or male patient does not entail differences in the effectiveness of the JAK inhibitor treatment. Our findings encourage the consideration of a global pool of composite indices (DAS28-ESR/CRP, CDAI, SDAI) to measure RA disease activity, thus individualizing the target value as advocated by the treat-to-target strategy. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Status and Future Challenges)

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17 pages, 2771 KiB

Open AccessArticle

Risk Factors Associated with Adverse Events Leading to Methotrexate Withdrawal in Elderly Rheumatoid Arthritis Patients: A Retrospective Cohort Study

by Felipe Alexis Avalos-Salgado, Laura Gonzalez-Lopez, Sergio Gonzalez-Vazquez, Juan Manuel Ponce-Guarneros, Aline Priscilla Santiago-Garcia, Edna Lizeth Amaya-Cabrera, Reynaldo Arellano-Cervantes, J. Ahuixotl Gutiérrez-Aceves, Miriam Fabiola Alcaraz-Lopez, Cesar Arturo Nava-Valdivia, Fabiola Gonzalez-Ponce, Norma Alejandra Rodriguez-Jimenez, Miguel Angel Macias-Islas, Edgar Ricardo Valdivia-Tangarife, Ana Miriam Saldaña-Cruz, Ernesto German Cardona-Muñoz and Jorge Ivan Gamez-Nava

J. Clin. Med. 2024, 13(7), 1863; https://doi.org/10.3390/jcm13071863 - 24 Mar 2024

Viewed by 1223

Abstract

Background: Rheumatoid arthritis (RA) in elderly population represents a challenge for physicians in terms of therapeutic management. Methotrexate (MTX) is the first-line treatment among conventional synthetic-disease-modifying anti-rheumatic drugs (cs-DMARDs); however, it is often associated with adverse events (AEs). Therefore, the objective of this study was to identify the incidence and risk factors of MTX discontinuation due to AEs in elderly patients with RA in a long-term retrospective cohort study. Methods: Clinical sheets from elderly RA patients taking MTX from an outpatient rheumatology consult in a university centre were reviewed. To assess MTX persistence, we used Kaplan–Meir curves and Cox regression models to identify the risk of withdrawing MTX due to adverse events. Results: In total, 198 elderly RA patients who reported using MTX were included. Of them, the rates of definitive suspension of MTX due to AEs were 23.0% at 5 years, 35.6% at 10 years and 51.7% at 15 years. The main organs and system involved were gastrointestinal (15.7%) and mucocutaneous (3.0%). Factors associated with withdrawing MTX due to AEs were MTX dose ≥ 15 mg/wk (adjusted HR: 2.46, 95% CI: 1.22–4.96, p = 0.012); instead, the folic acid supplementation was protective for withdrawal (adjusted HR: 0.28, 95% CI: 0.16–0.49, p < 0.001). Conclusions: Higher doses of MTX increase the risk of withdrawals in elderly RA, while folic acid supplementation reduces the risk. Therefore, physicians working in therapeutic management for elderly patients using MTX must focus on using lower MTX doses together with the concomitant prescription of folic acid. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Status and Future Challenges)

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17 pages, 1011 KiB

Open AccessArticle

Ultrasound-Guided Injections of HYADD4 for Knee Osteoarthritis Improves Pain and Functional Outcomes at 3, 6, and 12 Months without Changes in Measured Synovial Fluid, Serum Collagen Biomarkers, or Most Synovial Fluid Biomarker Proteins at 3 Months

by Richard T. Meehan, Mary T. Gill, Eric D. Hoffman, Claire M. Coeshott, Manuel D. Galvan, Molly L. Wolf, Isabelle A. Amigues, Liudmila M. Kastsianok, Elizabeth A. Regan, James L. Crooks, Gregory J. Czuczman and Vijaya Knight

J. Clin. Med. 2023, 12(17), 5541; https://doi.org/10.3390/jcm12175541 - 25 Aug 2023

Cited by 2 | Viewed by 1488

Abstract

Background: Prior studies have demonstrated improved efficacy when intra-articular (IA) therapeutics are injected using ultrasound (US) guidance. The aim of this study was to determine if clinical improvement in pain and function after IA hyaluronic acid injections using US is associated with changes in SF volumes and biomarker proteins at 3 months. Methods: 49 subjects with symptomatic knee OA, BMI < 40, and KL radiographic grade II or III participated. Subjects with adequate aspirated synovial fluid (SF) volumes received two US-guided IA-HA injections of HYADD4 (24 mg/3 mL) 7 days apart. Clinical evaluations at 3, 6, and 12 months included WOMAC, VAS, PCS scores, 6 MWD, and US-measured SF depth. SF and blood were collected at 3 months and analyzed for four serum OA biomarkers and fifteen SF proteins. Results: Statistical differences were observed at 3, 6, and 12 months compared to baseline values, with improvements at 12 months for WOMAC scores (50%), VAS (54%), and PCS scores (24%). MMP10 levels were lower at 3 months without changes in SF volumes, serum levels of C2C, COMP, HA, CPII, or SF levels of IL-1 ra, IL-4, 6, 7, 8, 15, 18, ILGFBP-1, 3, and MMP 1, 2, 3, 8, 9. Baseline clinical features or SF biomarker protein levels did not predict responsiveness at 3 months. Conclusions: Clinical improvements were observed at 12 months using US needle guidance for IA HA, whereas only one SF protein biomarker protein was different at 3 months. Larger studies are needed to identify which SF biomarkers will predict which individual OA patients will receive the greatest benefit from IA therapeutics. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Status and Future Challenges)

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Review

Jump to: Editorial, Research

10 pages, 269 KiB

Open AccessReview

Moving forward in Rheumatoid Arthritis-Associated Interstitial Lung Disease Screening

by Javier Narváez

J. Clin. Med. 2024, 13(18), 5385; https://doi.org/10.3390/jcm13185385 - 11 Sep 2024

Viewed by 684

Abstract

Patients with rheumatoid arthritis (RA) are at increased risk of developing interstitial lung disease compared to the general population, a complication that is associated with significant morbidity and high mortality. Given its frequency and severity, ILD should always be considered during both the initial assessment and follow-up of RA patients. However, there is currently no consensus on which RA patients should be screened for ILD. In recent years, several scientific societies have developed specific screening proposals. According to the recommendations of the Spanish, American, and Austrian rheumatology societies, it is not necessary to screen all individuals with RA, and it should be tailored to each patient based on clinical risk factors. In contrast, the Portuguese Societies of Rheumatology and Pulmonology advocate for systematic screening of all RA patients. Risk factors for the development of ILD in RA patients are well identified, and several screening tools for RA-ILD based on these risk factors have been developed. However, all of these tools still require further validation. To address this issue, the ANCHOR-RA study, a multinational cross-sectional initiative, has been launched to develop a multivariable model for predicting RA-ILD, which could provide valuable guidance for screening practices in clinical settings. In addition to certain biochemical and genetic predictive markers, lung ultrasound appears to be a useful screening tool. When combined with clinical evaluation and risk factor assessment, it can help identify which patients require a thoracic HRCT evaluation, which remains the gold standard for confirming an ILD diagnosis. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Status and Future Challenges)

16 pages, 308 KiB

Open AccessReview

Tailoring Rheumatoid Arthritis Treatment through a Sex and Gender Lens

by Loreto Carmona, Elena Aurrecoechea and María Jesús García de Yébenes

J. Clin. Med. 2024, 13(1), 55; https://doi.org/10.3390/jcm13010055 - 21 Dec 2023

Cited by 4 | Viewed by 1747

Abstract

Rheumatoid arthritis (RA) occurs more frequently in women than in men, and the studies that have addressed clinical and prognostic differences between the sexes are scarce and have contradictory results and methodological problems. The present work aims to evaluate sex- and gender-related differences in the clinical expression and prognosis of RA as well as on the impact on psychosocial variables, coping behavior, and healthcare use and access. By identifying between sex differences and gender-related outcomes in RA, it may be possible to design tailored therapeutic strategies that consider the differences and unmet needs. Being that sex, together with age, is the most relevant biomarker and health determinant, a so-called personalized medicine approach to RA must include clear guidance on what to do in case of differences. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Status and Future Challenges)

12 pages, 524 KiB

Open AccessReview

Initial Treatment with Biological Therapy in Rheumatoid Arthritis

by Jesús Tornero Molina, Blanca Hernández-Cruz and Héctor Corominas

J. Clin. Med. 2024, 13(1), 48; https://doi.org/10.3390/jcm13010048 - 21 Dec 2023

Cited by 2 | Viewed by 1985

Abstract

Background: We aimed to analyse the effectiveness, efficiency, and safety of initial treatment with biological therapies in rheumatoid arthritis (RA). Methods: Qualitative study. A group of RA experts was selected. A scoping review in Medline was conducted to analyse the evidence of initial RA treatment with biological therapies. Randomised clinical trials were selected. Two reviewers analysed the articles and compiled the data, whose quality was assessed using the Jadad scale. The experts discussed the review’s findings and generated a series of general principles: Results: Seventeen studies were included. Most of the included patients were middle-aged women with early RA (1–7 months) and multiple poor prognostic factors. Initial treatment with TNF-alpha inhibitors combined with methotrexate (MTX) and an IL6R inhibitor (either in mono or combination therapy) is effective (activity, function, radiographic damage, quality of life), safe, and superior to MTX monotherapy in the short and medium term. In the long term, patients who received initial treatment with biologicals presented better results than those whose initial therapy was with MTX. Conclusions: Initial treatment of RA with biological therapies is effective, efficient, and safe in the short, medium, and long term, particularly for patients with poor prognostic factors. Full article

(This article belongs to the Special Issue Rheumatoid Arthritis: Current Status and Future Challenges)

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