Predictive factors related to the progression of periodontal disease in patients with early rheumatoid arthritis: A cohort study

Background: Rheumatoid arthritis (RA) and periodontal disease are inter-related conditions. However, factors predictive of periodontal disease progression in patients with early rheumatoid arthritis (eRA) are lacking. The aim of this study was to identify factors associated with the progression of clinical attachment loss (CAL) in interproximal dental sites of eRA patients. Methods: Twenty-eight eRA patients were evaluated for the progression of CAL at 280 interproximal dental sites at 1 year of follow-up. Markers of RA activity (rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein), a marker of bone resorption (Dickkopf-related protein 1), Disease Activity Score 28 and Simple Disease Activity Index were included as potential systemic predictive factors. Plaque index, gingival index, pocket depth, clinical attachment level and Dickkopf-related protein 1 in crevicular fluid at baseline were included as potential local predictive factors. Data were analysed in a hierarchical structure using generalised linear mixed models for progression at each site (> 2 mm) during follow-up. Results: C-reactive protein level was the most important predictive systemic factor for the progression of CAL. The mean CAL and a high degree of gingival inflammation in interproximal sites at baseline were important predictive local factors (p < 0.0001). Patients who received combined treatment with disease-modifying antirheumatic drugs and corticosteroids exhibited less CAL (p < 0.0001). The predictive value of the generalised linear mixed model for progression was 85%. Conclusions: Systemic factors, including RA disease activity and baseline periodontal condition, were associated with periodontal progression. Pharmacological treatment may affect periodontal progression in patients with early RA

P050 Oral inflammatory changes associated with inflammatory bowel disease in spondyloarthritis associated with early endoscopic findings

BACKGROUND: Spondyloarthritis (SpA) is a heterogeneous group of chronic autoinflammatory disorders that can present extra-articular gastrointestinal manifestations. Among them is mainly inflammatory bowel disease (IBD). Although IBD mainly affects the intestinal tract, it can include early manifestations evident in the oral cavity. No comparative data on these oral manifestations in patients with SpA were found in the literature. OBJECTIVE: To identify oral clinical manifestations due to changes in the oral mucosa associated with IBD in patients with SpA without a diagnosis of IBD and associate them with endoscopic and histological findings. METHODS: 80 patients with SpA and 52 healthy controls were evaluated. They were assessed intra- and extra-orally, following the modified World Health Organization guideline. In addition, by clinical parameters of rheumatological, gastrointestinal and laboratory activity. Ileocolonoscopy was performed with digital chromoendoscopy with magnification and histological analysis. Comparative analyzes were performed by Chi square tests, Fisher's exact tests, confirmed by univariate regression and discriminant analysis of multiple correspondences. Institutional ethics committee approval cod-2017-023. RESULTS: The patients with SpA had 56% male gender, mean age of 42.8 years (SD ± 10.4) and a BMI in the range of 23.9 - 28.4. The healthy controls, 54% of the male gender with an average age of 41 years (SD ± 13.6) and a body mass index-BMI in the range of 22.9 - 27.6. The patients reported smoking only in 6.2%, however as a smoking history in 31% and passive smokers (15%), the majority employed (41%), married (56%) and professionals (49%). Of the healthy controls, they smoked (15%), with a history of smoking (31%), passive smokers (21%), the majority employed (77%), with their own home (67%), and professionals (54%). The patients with SpA reported a greater presence of some signs and symptoms of gastrointestinal origin 69%, while in the controls it was 7.7% (p = 0.001). Forty one of them were referred to colonoscopy with magnification being in 17.1 % changes in the mucosa of the rectum and in the same frequency changes in the mucosa of the sigmoid colon. Regarding the ileum, changes in the mucosa were evidenced in 41.5% of the cases. The presence of oral lesions was evident and predominated in them (63%) compared to controls p = 0.050. The main oral lesions associated with IBD were gingivitis (55%) (p = 0.001), followed by aphthous stomatitis (3.8%), angular cheilitis (2.6%) and perioral erythema with scaling (1.3%). 100% of the patients who presented alteration of the colonic mucosa presented oral lesions associated with IBD (p = 0039), which was also significantly associated with the presence of gingivitis/aphthous stomatitis (p = 0.029). CONCLUSION: Patients with SpA without a diagnosis of IBD have more oral signs and symptoms compared to healthy controls. Gingivitis is important given its association with early endoscopic and histological findings. Manifestations in the oral cavity can precede intestinal manifestations, therefore the clinical assessment by the oral pathologist in conjunction with gastroenterology and rheumatology allows a timely referral to gastroenterology and an endoscopic and histological evaluation, impacting the quality of life of patients

Trial of upadacitinib and adalimumab for psoriatic arthritis

Background: The Janus kinase inhibitor upadacitinib is a potential treatment for psoriatic arthritis. The efficacy and safety of upadacitinib as compared with adalimumab, a tumor necrosis factor α inhibitor, in patients who have an inadequate response to nonbiologic disease-modifying antirheumatic drugs are unclear. Methods: In a 24-week, phase 3 trial, we randomly assigned patients in a 1:1:1:1 ratio to receive oral upadacitinib at a dose of 15 mg or 30 mg once daily, placebo, or subcutaneous adalimumab (40 mg every other week). The primary end point was an American College of Rheumatology 20 (ACR20) response (≥20% decrease in the number of tender and swollen joints and ≥20% improvement in at least three of five other domains) at week 12 with upadacitinib as compared with placebo. Secondary end points included comparisons of upadacitinib with adalimumab. Results: A total of 1704 patients received an active drug or placebo. The percentage of patients who had an ACR20 response at week 12 was 70.6% with 15-mg upadacitinib, 78.5% with 30-mg upadacitinib, 36.2% with placebo (P&lt;0.001 for both upadacitinib doses vs. placebo), and 65.0% with adalimumab. The difference between groups for 15-mg upadacitinib as compared with adalimumab was 5.6 percentage points (95% confidence interval [CI], −0.6 to 11.8) and for 30-mg upadacitinib as compared with adalimumab was 13.5 percentage points (95% CI, 7.5 to 19.4). Both upadacitinib doses were noninferior to adalimumab for the ACR20 response at week 12; the 30-mg dose but not the 15-mg dose was superior to adalimumab. The incidence of adverse events through week 24 was 66.9% with 15-mg upadacitinib, 72.3% with 30-mg upadacitinib, 59.6% with placebo, and 64.8% with adalimumab. There were serious infections in 1.2%, 2.6%, 0.9%, and 0.7% of the patients, respectively. Hepatic disorders occurred in 9.1% of patients in the 15-mg upadacitinib group and 12.3% in the 30-mg upadacitinib group, but grade 3 increases in aminotransferase levels occurred in 2% of patients or fewer in all groups. Conclusions: The percentage of patients with psoriatic arthritis who had an ACR20 response at week 12 was significantly higher with 15-mg or 30-mg upadacitinib than with placebo. The 30-mg dose but not the 15-mg dose was superior to adalimumab. Adverse events were more frequent with upadacitinib than with placebo. (Funded by AbbVie; SELECT-PsA 1 ClinicalTrials.gov number, NCT03104400.)

Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis:Sixteen-Week Results From a Phase III Randomized, Double-Blind, Placebo-Controlled Trial in Patients With Prior Inadequate Response to or Intolerance of Tumor Necrosis Factor Inhibitors

Objective: To investigate the efficacy and safety of ixekizumab in patients with active radiographic axial spondyloarthritis (SpA) and prior inadequate response to or intolerance of 1 or 2 tumor necrosis factor inhibitors (TNFi). Methods: In this phase III randomized, double-blind, placebo-controlled trial, adult patients with an inadequate response to or intolerance of 1 or 2 TNFi and an established diagnosis of axial SpA (according to the Assessment of SpondyloArthritis international Society [ASAS] criteria for radiographic axial SpA, with radiographic sacroiliitis defined according to the modified New York criteria and ≥1 feature of SpA) were recruited and randomized 1:1:1 to receive placebo or 80-mg subcutaneous ixekizumab every 2 weeks (IXEQ2W) or 4 weeks (IXEQ4W), with an 80-mg or 160-mg starting dose. The primary end point was 40% improvement in disease activity according to the ASAS criteria (ASAS40) at week 16. Secondary outcomes and safety were also assessed. Results: A total of 316 patients were randomized to receive placebo (n = 104), IXEQ2W (n = 98), or IXEQ4W (n = 114). At week 16, significantly higher proportions of IXEQ2W patients (n = 30 [30.6%]; P = 0.003) or IXEQ4W patients (n = 29 [25.4%]; P = 0.017) had achieved an ASAS40 response versus the placebo group (n = 13 [12.5%]), with statistically significant differences reported as early as week 1 with ixekizumab treatment. Statistically significant improvements in disease activity, function, quality of life, and spinal magnetic resonance imaging–evident inflammation were observed after 16 weeks of ixekizumab treatment versus placebo. Treatment-emergent adverse events (AEs) with ixekizumab treatment were more frequent than with placebo. Serious AEs were similar across treatment arms. One death was reported (IXEQ2W group). Conclusion: Ixekizumab treatment for 16 weeks in patients with active radiographic axial SpA and previous inadequate response to or intolerance of 1 or 2 TNFi yields rapid and significant improvements in the signs and symptoms of radiographic axial SpA versus placebo

Immunoadjuvant Therapy and Noninvasive Ventilation for Acute Respiratory Failure in Lung Tuberculosis: A Case Study

Acute respiratory failure caused by pulmonary tuberculosis is a rare event but with a high mortality even while receiving mechanical ventilatory support. We report the case of a young man with severe pulmonary tuberculosis refractory to conventional therapy who successfully overcame the critical period of his condition using noninvasive ventilation and immunoadjuvant therapy that included three doses of etanercept 25 mg subcutaneously. We conclude that the use of etanercept along with antituberculosis treatment appears to be safe and effective in patients with pulmonary tuberculosis presenting with acute respiratory failure

Factors Associated to Clinical and Radiographic Disease Progression in Patients with Early RA and First-degree Relatives: A 1-year Follow-up

In rheumatoid arthritis (RA), autoimmunity towards citrullinated peptides driven the hypothesis, in which periodontal disease (PD) is strongly related to the pathogenesis. Given the genetic association, first degree relatives (FDR) of RA-patients are considered a high-risk population to develop RA. The objective is to assess the evolution of clinical disease activity and radiographic progression associated with PD in early RA (eRA) and FDR at one-year follow-u

Efficacy and safety of tregalizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase IIb, randomised, placebo-controlled trial

To evaluate the efficacy, biological activity and safety of tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). 321 patients were randomised (1:1:1:1) to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in addition to MTX treatment. Responders at week 12 continued the same treatment, and non-responders at week 12 were escalated to the next higher tregalizumab dose level or re-randomised from placebo to active treatment. After 24 weeks, patients could continue treatment with tregalizumab for 24 weeks (extension phase). The primary endpoint was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Safety and biological activity were monitored through week 48. At week 12, ACR20 response rates were not statistically significantly different between placebo and any of the tregalizumab doses. Tregalizumab injections were well tolerated; most adverse events were mild to moderate and comparable among treatment and placebo groups. Biological activity was shown by dose-dependent CD4 downmodulation. Treatment with tregalizumab did not show significant clinical efficacy in patients with active RA compared with placebo but resulted in the expected biological effect on CD4 modulation. Tregalizumab was generally well tolerated, and no new safety findings were identified. NCT01999192; Result

<i>PADI4</i> Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico

Citrullination is catalyzed by the peptidyl arginine deiminase 4 (PAD4) enzyme, encoded by the PADI4 gene. Increased PAD4 activity promotes the onset and progression of rheumatoid arthritis (RA). This study aimed to evaluate the association of PADI4 haplotypes with RA risk, mRNA expression, and the PAD4 activity in patients with RA from Mexico. Methodology: 100 RA patients and 100 control subjects (CS) were included. Genotyping was performed by PCR-RFLP method, PADI4 mRNA expression was quantified by real-time PCR, the contribution of PADI4 alleles (PADI4_89 G>A, PADI4_90 T>C, and PADI4_92 G>C) to mRNA expression by the ASTQ method, and PAD4 activity by HPLC. Also, the anti-CCP and anti-PADI4 antibodies were quantified by ELISA. Results: The three PADI4 polymorphisms were associated with RA susceptibility (OR = 1.72, p = 0.005; OR = 1.62; p = 0.014; OR = 1.69; p = 0.009; respectively). The 89G, 90T, and 92G alleles have a higher relative contribution to PADI4 mRNA expression from RA patients than 89A, 90C, and 92C alleles in RA patients. Moreover, the GTG/GTG haplotype was associated with RA susceptibility (OR = 2.86; p = 0.024). The GTG haplotype was associated with higher PADI4 mRNA expression (p = 0.04) and higher PAD4 enzymatic activity (p = 0.007) in RA patients. Conclusions: The evaluated polymorphisms contribute to PADI4 mRNA expression and the enzymatic activity of PAD4 in leukocytes. Therefore, the GTG haplotype is a genetic risk factor for RA in western Mexico, and is associated with increased PADI4 mRNA expression and higher PAD4 activity in these patients