Rheumato, Volume 6, Issue 1 (March 2026) – 8 articles

Objectives: The evidence for treating rheumatoid arthritis (RA) with a treat-to-target (T2T) approach was examined for clinical outcomes. Methods: Since August 2010, RA treatment has implemented the T2T strategy, aiming to achieve a simplified disease activity index (SDAI). The SDAI, Health Assessment Questionnaire Disability Index (HAQ), and pain score (PS-VAS) were monitored. The relationships between these clinical outcomes and variables, including changes in medication, were investigated. Results: Over a 15-year follow-up of 764 RA patients, the total duration was divided into two periods for each outcome. In the First period, the average dose of methotrexate (MTX) increased (p < 0.001). At the same time, glucocorticoids use (GCs) decreased (p < 0.001), and biologic and targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs and tsDMARDs) use increased (p < 0.01). Consequently, the mean SDAI score declined (p < 0.001), which was attributed to an increase in MTX dose and a decrease in GCs use, However, HAQ scores increased (p < 0.01), and PS-VAS remain stable. In the Second period, the average MTX dose decreased despite stable SDAI and decreasing HAQ scores and PS-VAS (p < 0.01), which was attributed to an increase in the use of tsDMARDs, particularly baricitinib, upadacitinib, and filgotinib (p < 0.01). Overall, the average age increased (p < 0.001), while SDAI scores dropped (p < 0.001), and HAQ scores and PS-VAS decreased (p < 0.01). Conclusions: Clinical outcomes stayed stable with changes in medication use under the T2T approach. Full article

Background/Objectives: The short-term effect of Janus kinase inhibitors (JAKis) on renal function in patients with rheumatoid arthritis (RA) was examined in a hypothesis-generating, exploratory study. Methods: RA patients treated with JAK inhibitors and, as a control group, those receiving golimumab and continuing treatment for one or more years were enrolled. They were monitored every 3 months for disease activity using the Simplified Disease Activity Index (SDAI), functional capacity using the Health Assessment Questionnaire Disability Index (HAQ), and renal function using the estimated glomerular filtration rate (eGFR) calculated from creatinine (Cr) and cystatin C (CysC). Patients were categorized by medication, and average values were computed. Two groups for each drug were then compared statistically. Results: A total of 144 patients were analyzed: 24 on tofacitinib, 43 on baricitinib, 21 on upadacitinib, 21 on filgotinib, and 35 on golimumab. Background factors did not differ significantly among groups. Improvements in CDAI and HAQ at any time point also showed no significant differences. eGFR based on Cr showed a significant decline in the baricitinib and filgotinib groups at one year after starting JAKi treatment compared with the other JAKi groups; however, there was no significant difference when using CysC. Conclusions: These results indicate that there is no significant difference in renal function decline among the JAKi drugs over a short period, despite differences in their metabolic pathways and renal excretion patterns. Full article

Background: Autoinflammatory bone disorders are rare, non-infectious inflammatory conditions that primarily involve the skeleton, most commonly presenting as chronic nonbacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO). Less frequently, they occur in the context of Mendelian syndromes such as Majeed syndrome, deficiency of the interleukin-1 receptor antagonist (DIRA), and pyogenic arthritis; pyoderma gangrenosum; and acne (PAPA) syndrome. Given the role of IL-1-driven innate immune dysregulation across these bone disorders, and the growing, though heterogeneous, clinical experience with IL-1 blockade, this review maps and critically appraises the available evidence on canakinumab in autoinflammatory bone disorders. Methods: We systematically searched PubMed and the Cochrane Library (English, inception–July 2025) and screened ClinicalTrials.gov. Eligible reports included any case reports/series describing canakinumab use in autoinflammatory bone disorders (CNO/CRMO, Majeed, DIRA, PAPA). Results: Six publications met the inclusion criteria (one case series, five case reports; 10 patients). Complete responses were reported in all three patients with Majeed syndrome and in two patients with sporadic CRMO associated with systemic features. Partial responses occurred in two additional sporadic CRMO cases, while no meaningful response was documented in DIRA. No interventional trials of canakinumab were identified on ClinicalTrials.gov for CNO/CRMO, Majeed, DIRA, or PAPA. Conclusions: Although the role of IL-1 in the pathogenesis of autoinflammatory bone disease provides a rationale for IL-1 blockade, evidence for canakinumab remains limited and heterogeneous, precluding definitive conclusions. Indicators of benefits appear most consistently in Majeed syndrome and in selected CRMO phenotypes. Full article

Background/Objectives: Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain, fatigue, sleep disturbances, and psychological symptoms. Aquatic exercise offers the benefits of physical activity with reduced mechanical stress. This meta-analysis evaluated the effectiveness of AE on pain, functional physical status, and health-related quality of life. Methods: A PRISMA-guided systematic review and meta-analysis (PROSPERO CRD42025115158) included randomized and non-randomized trials up to October 2025 from MEDLINE (PubMed), Cochrane Library, PEDro, CINAHL Complete, SPORTDiscus, and Academic Search Ultimate. Eligible participants were adults diagnosed with FMS undergoing AE programs, alone or combined with other modalities. Standardized mean differences (SMD) with 95% confidence intervals were pooled using random- or fixed-effects models. Methodological quality, risk of bias, and certainty of evidence were evaluated using the PEDro scale, the RoB 2.0 tool, and the GRADE approach. Results: 27 trials (n = 1785; >95% women; mean age 44–62 years) were included. AE significantly improved pain (SMD = −0.92; 95% CI: −1.03 to −0.80; p < 0.00001), physical function (SMD = −0.74; 95% CI: −0.84 to −0.63; p < 0.00001), and HRQoL (SMD = 0.57; 95% CI: 0.42 to 0.72; p < 0.00001). Effects were consistent across time frames, though overall heterogeneity was considerable (Tau² = 4.93; I² = 97%). The mean PEDro score was 5.2/10, and RoB 2.0 indicated moderate methodological limitations mainly due to a lack of blinding. Evidence certainty was low for the main outcomes and moderate for adverse events. Conclusions: Aquatic exercise is an effective and safe complementary therapy for patients with FMS, alleviating pain while enhancing function and quality of life. However, methodological variability and small sample sizes warrant further high-quality trials to confirm these findings and explore underlying mechanisms. Full article

Background: Immunomodulatory therapies, including biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) have reshaped the treatment of autoimmune diseases. They alter host defenses, but the current landscape of associated infectious risk is not fully defined. Objective: A scoping review of recent literature was conducted to characterize infectious complications associated with modern immunomodulatory biologic agents, summarize current pathogen patterns, and highlight recommendations for prevention and early recognition in clinical practice. Methods: Following PRISMA-ScR guidelines, a systematic search was performed on Scopus, Science Direct, and PubMed for studies published since 2023. Inclusion criteria focused on adult human subjects, exposure to immunomodulatory therapy, and reported infectious outcomes. Studies focusing exclusively on antineoplastic agents without established use in autoimmune diseases were excluded. After screening 1046 unique records, 16 studies were included in the final review. Findings: High-dose glucocorticoids remain a primary driver of serious infections across autoimmune diseases. Newer agents present mechanism-specific risk profiles. JAK inhibitors are associated with herpes zoster, while TNF-α inhibitors are linked to opportunistic bacterial infections and reactivation of granulomatous infections. B-cell depletion with rituximab correlates with hypogammaglobulinemia and its associated infections, whereas belimumab may offer a lower infection risk in non-renal SLE. Recent post hoc analyses (2023–2025) quantify the elevated risk of herpes zoster with JAK inhibitors compared to TNF inhibitors, particularly in older populations. Conclusions: The infectious risk associated with biologic and targeted DMARDs varies by mechanism. While glucocorticoids remain a primary driver of serious infections, newer data highlights specific vulnerabilities with JAK inhibitors (herpes zoster) and B-cell depletion (hypogammaglobulinemia) that require targeted risk stratification. This review shows the urgent need for individualized risk stratification, targeted prophylaxis (e.g., for Pneumocystis or zoster), and pre-therapy screening to balance therapeutic efficacy with patient safety. Full article

Pain catastrophizing (PC) and hopelessness are increasingly recognized as central determinants of pain severity, disability, and treatment response in individuals with rheumatic and immune-mediated diseases. Traditionally conceptualized as secondary emotional reactions to pain, these cognitive-affective constructs instead represent active mechanisms that shape symptom perception, behavioral responses, and long-term outcomes. In this review, we synthesize evidence across neurobiological, psychological, and clinical domains to elucidate the pathways linking PC and hopelessness to maladaptive coping, kinesiophobia, and functional decline. Early life stress, trauma, and maladaptive cognitive schemas emerge as upstream vulnerability factors that prime heightened emotional reactivity and reduced prefrontal regulatory control, facilitating amplified pain signaling and fear-based avoidance behaviors. Avoidance and inactivity foster physical deconditioning, fatigue, and higher perceived disability, creating a vicious circle that sustains distress and poor quality of life. Moreover, inactivity-related metabolic dysfunction and weight gain may contribute to low-grade inflammation, particularly in conditions such as psoriatic arthritis, thereby intersecting with biological disease pathways. Importantly, these psychological processes identify a distinct patient subgroup for whom further escalation of immunosuppressive therapy provides limited benefit. Instead, integrated psychological approaches—including cognitive behavioral therapy, acceptance and commitment therapy, and coping-skills training—demonstrate meaningful effects on catastrophizing, agency, and functional recovery. We emphasize the need for routine screening to detect patients with maladaptive cognitive–emotional profiles and propose a stratified care model prioritizing targeted psychological interventions alongside standard rheumatologic therapy. Future research should refine phenotyping strategies, clarify neuroimmune links, and develop scalable intervention models to break the avoidance cycle and improve patient-centered outcomes. Full article

Background/Objectives: The aim of this study was to assess the relationship between the decline in rheumatoid arthritis (RA) disease activity—induced by periodontal treatment—and changes in the microbiology of subgingival plaque and serum antibody levels against the periodontal bacterium Porphyromonas gingivalis. Methods: Twenty-two RA patients with periodontitis underwent non-surgical periodontal treatment and assessment for the disease activity score of 28 joints (DAS28); antibody response to P. gingivalis virulence factors arginine (Rgp) and lysin (Kgp) gingipain; peptidyl arginine deiminase (PAD)2/4-activity; and the presence of P. gingivalis, Tannerella forsythia, and Prevotella intermedia in subgingival plaque through the evaluation of colony-forming units (CFUs) at baseline, two months, and six months post-treatment. Results: Periodontal treatment significantly reduced P. gingivalis CFUs at two and six months, and T. forsythia and P. intermedia CFUs at two months. Anti-RgpB IgG levels decreased at two months (p = 0.020). Higher baseline anti-RgpB IgG levels (r = −0.44, p = 0.039) and P. gingivalis CFU (r = −0.47, p = 0.028) correlated with greater reductions in DAS28. Greater reductions in P. gingivalis CFU were also associated with greater declines in DAS28 (r = 0.426, p = 0.048 and r = 0.467, p = 0.028, at two and six months, respectively). Anti-Kgp IgG and PAD2/PAD4 activity were not significantly affected by periodontal treatment. Conclusions: The impact of periodontal treatment on RA disease activity is more pronounced in patients with higher baseline P. gingivalis load and antibody response to RgpB. Better microbiological responses to periodontal treatment are associated with greater improvements in rheumatological symptoms. Further research is needed to confirm these findings and fully elucidate the underlying mechanisms. Full article

Background/Objectives: Associations between renal function, as measured by the estimated glomerular filtration rate (eGFR) or its decline (dGFR), and clinical parameters in patients with rheumatoid arthritis (RA) were evaluated using a retrospective case–control series dataset. Methods: Patients with RA who followed up for one or more consecutive years were recruited for the study. For calculating the eGFR, cystatin C (CysC) was adopted. The moment when CysC was measured was set as the baseline. The association between the eGFR and baseline clinical parameters, including disease activity in RA as measured by the simplified disease activity index (SDAI), was statistically evaluated. The association between the mean annual decline in the eGFR from the baseline and clinical parameters was also statistically assessed. Results: A total of 513 patients were enrolled; with a mean age of 70.9; a mean follow-up length of 52.5 months; a mean BMI of 22.9; a 68.7 eGFR; and a mean annual dGFR of 2.74. Significant parameters that correlated with the eGFR were age; rheumatoid factor titer; C-reactive protein; the presence of hypertension; chronic heart failure; chronic obstructive pulmonary disease; type 2 diabetes mellitus; methotrexate administration; and polypharmacy at baseline. An annual dGFR was correlated with the follow-up length, and the mean SDAI score multiplied by the yearly length of the follow-up was significantly correlated. Conclusions: Many factors confound the determination of the eGFR in RA patients. The disease activity score and length of time are the key factors for declining eGFRs. Full article