Ankylosing Spondylitis Disease Activity Research Articles

Efficacy and Safety of Tofacitinib in Patients with Psoriatic Arthritis or Ankylosing Spondylitis by Cigarette Smoking Status.

Routine care studies of psoriatic arthritis (PsA) and ankylosing spondylitis (AS) demonstrated attenuated responses to tumor necrosis factor inhibitors in current/past versus never smokers. This post hoc analysis assessed tofacitinib efficacy and safety in patients with PsA or AS by cigarette smoking status at trial screening. Pooled data from phase 3 and long-term extension (safety only) PsA trials and phase2 and 3 AS trials were assessed by current/past versus never smoker status. Analysis included efficacy and safety data for tofacitinib 5 (PsA/AS) and 10(PsA only) mg twicedaily (BID) or placebo, and safety data in AS for tofacitinib 2 and 10 mg BID. Efficacy outcomes included American College of Rheumatology ≥ 50% responses (ACR50) and minimal disease activity (MDA) responses to month (M)6/M3 (tofacitinib/placebo) in PsA; and ≥ 40% improvement in Assessment of SpondyloArthritis international Society responses (ASAS40) and AS Disease Activity Score (ASDAS) < 2.1 responses to week (W)16 in AS. Safety was assessed to M48/W48 (PsA/AS), adjusted for treatment/smoking status/median body mass index (BMI) status/sex/trial/treatment-smoking status interaction. PsA/AS cohorts included 342/178 current/past and 572/194 never smokers. Tofacitinib efficacy was generally greater versus placebo to M3/W6 (PsA/AS), and comparable in current/past and never smokers to M6/W16 (PsA/AS). In patients receiving ≥ 1tofacitinib dose, adjusted treatment-emergent adverse event (TEAE)/serious AE (SAE)/discontinuation due to AE incidence rates (IRs) to M48 in PsA were higher in current/past versus never smokers; adjusted IRs to W48 in AS were higher in current/past versus never smokers for TEAEs, but similar for SAEs/discontinuation due to AEs. In both patients with PsA and AS, tofacitinib efficacy was greater versus placebo, and comparable across smoking categories. Adjusted IRs were higher in current/past versus never smokers for TEAEs, SAEs, discontinuation due to AEs in PsA, and for TEAEs in AS, complementing reports of associations between smoking and comorbidities in spondyloarthritis. Findings support increased surveillance/caution for patients with PsA or AS with smoking history. ClinicalTrials.gov: NCT01877668/NCT01882439/NCT03486457/NCT01976364/NCT01786668/NCT03502616.

18F-FDG positron emission tomography as a marker of disease activity and treatment response in ankylosing spondylitis and psoriatic arthritis

The ability of 18F-FDG positron emission tomography (PET) to track disease activity and treatment response in patients with Ankylosing Spondylitis (AS) or Psoriatic Arthritis (PsA) remains unclear. Here, we assessed whether 18F-FDG uptake is a marker of disease activity and treatment response in AS or PsA, and explored the ability of 18F-FDG to predict treatment response. Patients with AS (n = 16) or PsA (n = 8) who were scheduled to initiate treatment with biologics were recruited. Participants underwent a clinical evaluation and an 18F-FDG scan prior to therapy initiation. Eleven participants underwent a follow-up 18F-FDG scan 3 months post-treatment. Images were quantified using a composite measure that describes the inflammatory status of the patient. Clinically involved joints/entheses had higher 18F-FDG uptake compared to unaffected areas (median difference > 0.6, p < 0.01). Among patients with AS, pre-treatment 18F-FDG uptake was strongly associated with disease activity (r = 0.65, p = 0.006). Longitudinal 18F-FDG scans demonstrated that decreases in uptake at 3 months were associated to clinical response (βΔgSUVmax > 8.5, p < 0.001). We found no significant association between pre-treatment 18F-FDG uptake and subsequent clinical response. 18F-FDG PET shows potential as a marker of disease activity in AS and PsA, allowing for monitorization of biological treatment efficacy in these patients.

Egyptian patients with axial spondyloarthritis: The frequency and predictors of renal impairment

Aim of the workTo determine the frequency of and risk factors for renal impairment in patients with axial spondyloarthritis (axSpA). Patients and methodsFifty axSpA patients participated in this study. In accordance with the Kidney Disease Outcomes Quality Initiative (K/DOQI) criteria, patients were split into two groups: group 1comprised renal impairment and group 2 comprised non-renal impairment. The ankylosing spondylitis (AS) disease activity score (ASDAS), Bath AS disease activity index (BASDAI) and estimated glomerular filtration rate were assessed. ResultsThe mean age of patients was 38.9 ± 11.7 years, males were 54 % and the disease duration was 11.36 ± 6.1 years. The mean ASDAS score was 5.58 ± 1.38 and BASDAI was 5.18 ± 1.55. The eGFR was 76.4 ± 36.2 ml/min/1.73 m2 and 28 % had positive human leucocytic antigen (HLA-B27). 80 % were receiving biologic therapy. Nephropathy by ultrasound and renal impairment were detected in 34 % and 52 % of the cases respectively. The cumulative dose of non-steroidal anti-inflammatory drugs (NSAIDs), C-reactive protein, erythrocyte sedimentation rate, low density cholesterol, blood urea nitrogen, creatinine, proteinuria, ASDAS and BASDAI were significantly higher in those with renal impairment(p = 0.0001, p = 0.0001, p = 0.001, p = 0.035, p = 0.0001, p = 0.0001, p = 0.0001, p = 0.001, p = 0.001 respectively) while the eGFR and high density lipoprotein were significantly lower (p = 0.001and p = 0.02). Only the cumulative dose of NSAIDs was a significantly independent variable influencing the development of renal impairment (OR=1.01, CI; 1.001–1.02, p = 0.024) at cut-off level > 1166.3 g. ConclusionsRenal impairment is frequent in axSpA patients with decreased eGFR and high disease activity. The cumulative dose of NSAIDs is a significant predictor of renal impairment.

T2* cartilage mapping in early axial spondyloarthritis: diagnostic accuracy and correlation with clinical characteristics, sacroiliitis MRI scorings, and diffusion metrics.

To determine the performance of T2* cartilage mapping in diagnosing and assessing disease activity in early axial spondyloarthritis (axSpA), and to investigate the interaction of cartilage damage with clinical characteristics, sacroiliitis MRI scorings, and diffusion metrics. This prospective study included 83 axSpA patients and 37 no-axSpA patients. Clinical characteristics, the Assessment of SpondyloArthritis International Society-defined active sacroiliitis on MRI, and T2* SIJs values were recorded. In axSpA, disease activity was evaluated using the ankylosing spondylitis disease activity score-C-reactive protein; active sacroiliitis was evaluated using Spondyloarthritis Research Consortium of Canada, intravoxel incoherent motion, and diffusion kurtosis imaging; chronic sacroiliitis was assessed using composite structural damage score (CSDS) and structural score fat. Mann-Whitney U-test, Kruskal-Wallis test with false discovery rate (FDR), ROC curve, and linear regression were used for statistical analysis. AxSpA patients had significantly higher T2*SIJs values than no-axSpA patients. (22.86 ± 2.42 ms vs 20.36 ± 1.30 ms, p < 0.001). The combination of T2*SIJs values and active sacroiliitis on MRI had the highest AUC for identifying axSpA. T2*SIJs values were significantly different between the inactive and very high, moderate and very high, high and very high, as well as inactive and high disease activity groups (all pFDR < 0.05). Dk (β = 0.48) and CSDS (β = 0.48) were independently associated with T2*SIJs values. T2* values may be a promising biomarker for diagnosing and differentiating disease activity in early axSpA. Both acute and chronic sacroiliitis influence cartilage properties. Sacroiliac joint cartilage abnormalities can be quantified with T2* relaxation time and allow better characterization of early axSpA. T2* mapping may have value in evaluating axSpA. The combination of T2* values and active sacroiliitis on MRI enhances diagnostic performance for axSpA. Abnormalities measured with T2* values correlate with disease activity, acute sacroiliitis, and degree of structural damage.

Effects of serum inflammatory factors, health index and disease activity scores on ankylosing spondylitis patients with sleep disorder

BACKGROUND Patients with ankylosing spondylitis (AS) frequently suffer from comorbid sleep disorders, exacerbating the burden of the disease and affecting their quality of life. AIM To investigate the clinical significance of serum inflammatory factors, health index and disease activity scores in patients with AS complicated by sleep disorders. METHODS A total of 106 AS patients with comorbid sleep disorders were included in the study. The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes. The serum levels of inflammatory factors, including C-reactive protein, erythrocyte sedimentation rate, interleukin (IL)-6, tumour necrosis factor-α and IL-1β, were measured. Disease activity scores, such as the Bath AS functional index, Bath AS disease activity index, Bath AS metrology index and AS disease activity score, were assessed. The health index was obtained through the Short Form-36 questionnaire. RESULTS The study found significant associations amongst serum inflammatory factors, health index and disease activity scores in AS patients with comorbid sleep disorders. Positive correlations were found between serum inflammatory factors and disease activity scores, indicating the influence of heightened systemic inflammation on disease severity and functional impairment. Conversely, negative correlations were found between disease activity scores and health index parameters, highlighting the effect of disease activity on various aspects of health-related quality of life. Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes, underscoring their potential utility in risk assessment and prognostication. CONCLUSION The findings demonstrate the intricate interplay amongst disease activity, systemic inflammation and patient-reported health outcomes in AS patients complicated by sleep disorders. The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors, health index and disease activity scores as prognostic markers in this patient population.

Efficacy and Safety of Tofacitinib in Ankylosing Spondylitis by Baseline C-Reactive Protein Level: Post Hoc Analysis of Phase II and Phase III Clinical Trials.

This post hoc analysis assessed the effect of baseline C-reactive protein (CRP) on the efficacy and safety of tofacitinib (TOF) use in ankylosing spondylitis (AS), as well as patient-reported outcomes (PROs). Phase II (ClinicalTrials.gov: NCT01786668) and phase III (ClinicalTrials.gov: NCT03502616) data from patients with active AS were used. Endpoints (weeks 12, 16, and 48), including 20% and 40% improvement in Assessment of SpondyloArthritis international Society (ASAS), AS Disease Activity Score with CRP low disease activity, 50% improvement in Bath AS Disease Activity Index (BASDAI50), and PROs (pain and fatigue), were stratified by baseline CRP (mg/L) as follows: < 5 (normal), ≥ 5 (elevated), < 10, and ≥ 10. Safety outcomes were evaluated between < 5 and ≥ 5 mg/L subgroups. Overall, 372 patients were included (69.6% ≥ 5mg/L; 50.8% ≥ 10 mg/L). At baseline in the < 5mg/L group, more placebo-treated than TOF-treated patients received concomitant nonsteroidal antiinflammatory drugs (NSAIDs) or sulfasalazine (SSZ). Week 12 efficacy and PRO responses were generally higher for TOF vs placebo, regardless of baseline CRP. The treatment effect (placebo-adjusted response) at week 12 was generally numerically higher in ≥ 5 mg/L and ≥ 10 mg/L vs < 5 mg/L and < 10 mg/L groups. Incidence rates for treatment-emergent adverse events (TEAEs) and "all infections" were numerically higher for TOF vs placebo in patients in the < 5 mg/L group, but similar for TOF vs placebo in patients in the ≥ 5 mg/L group. Regardless of baseline CRP, TOF was more efficacious vs placebo at week 12. The placebo-adjusted efficacy and PRO responses were generally numerically higher in patients with CRP ≥ 5 mg/L and ≥ 10 mg/L vs < 5 mg/L and < 10 mg/L. The higher concomitant NSAID/SSZ exposure may have improved efficacy responses in the baseline < 5 mg/L placebo group, and ultimately affected the TOF treatment effect. Safety was consistent with previous studies of TOF use in AS, with numerically higher incidence rates for TEAEs and "all infections" for TOF vs placebo in patients with CRP < 5 mg/L.

Time to improvement of pain, morning stiffness, fatigue, and disease activity in patients with ankylosing spondylitis treated with tofacitinib: a post hoc analysis

BackgroundTofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Time to improvement in core domains of AS was estimated in tofacitinib-treated patients with AS.MethodsThis post hoc analysis used phase 3 trial data from patients with AS receiving tofacitinib 5 mg twice daily or placebo to week (W)16; all patients received open-label tofacitinib W16–48. Outcomes: nocturnal pain; total back pain; fatigue, spinal pain, peripheral joint pain/swelling, enthesitis, and morning stiffness (Bath AS Disease Activity Index [BASDAI] questions 1–6); BASDAI total score; AS Disease Activity Score (ASDAS). Median time to improvement events was estimated using non-parametric Kaplan-Meier models. Improvement events were defined as initial (first post-baseline observation) and continued (sustained for 2 consecutive visits) ≥ 30% and ≥ 50% improvement in back/nocturnal pain or BASDAI questions/total scores, or ASDAS improvement ≥ 1.1 and ≥ 2.0 points.Results269 patients (tofacitinib: n = 133; placebo-to-tofacitinib: n = 136) were assessed. Median time to improvement was shorter, and more patients experienced improvements with tofacitinib vs. placebo-to-tofacitinib; differences observed from W2 (first post-baseline assessment). Median time to initial (continued) ≥ 30% pain improvement was 4 (4–8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib (8 [8] weeks post-switch). Median time to initial (continued) ≥ 50% improvement of pain, peripheral joint pain/swelling and enthesitis, morning stiffness, BASDAI total score, and fatigue was 8–24 (12–40) weeks with tofacitinib vs. 24–32 weeks (32 weeks–not estimable [NE]) with placebo-to-tofacitinib. Median time to initial (continued) ASDAS improvement ≥ 1.1 points was 4 (8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib, and NE for improvement ≥ 2.0 points with either treatment.ConclusionsImprovements in AS core domains occurred more rapidly with tofacitinib vs. placebo-to-tofacitinib. Half of tofacitinib-treated patients with AS will likely experience improvements ≥ 30% in pain and ≥ 1.1 points in ASDAS during month (M)1, ≥ 50% improvement in nocturnal pain and enthesitis by M2, and in morning stiffness by M3. Results show that initiating tofacitinib as soon as possible is associated with quicker improvements in AS core domains vs. delaying treatment.Trial registrationClinicalTrials.gov, NCT03502616, 11 April 2018.

Clinical value of the Patient Global Assessment with Ankylosing Spondylitis: A cross-sectional study.

To analyze the factors associated with the overall patient condition and explore the clinical value of the Patient Global Assessment (PGA) index for assessing the disease state in patients with Ankylosing Spondylitis (AS). This cross-sectional study used a standardized questionnaire to record the basic information of patients with AS. The collected data included the Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP), ASDAS-erythrocyte sedimentation rate (ESR), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), PGA, and other clinical indicators. Statistical analysis was performed using SPSS 25.0 software, and the scale was assessed for retest reliability and structural validity. The Kruskal-Wallis H test and Spearman or Pearson correlation analysis were used to analyze the factors influencing PGA scores. The receiver operator characteristic (ROC) curve was used to identify the cutoff value of the PGA for predicting disease activity in AS. The patient age, disease duration, family history, and history of ocular inflammation significantly differed between PGA groups (P < .05). The median PGA was significantly lower in patients with disease remission than in those with disease activity (P < .01). The various clinical indexes significantly differed between PGA groups (P < .01). The PGA was significantly correlated with various clinical indicators (P < .01). The area under the ROC curve (AUC) for disease activity based on the ASDAS-CRP was 0.743 (P < .01) with a PGA cutoff value of 1.38; the AUC for disease activity based on the BASDAI was 0.715 (P < .01) with a PGA cutoff value of 1.63. The PGA was significantly correlated with patient-reported outcomes, disease activity, function, and psychological status, and may indicate the level of inflammation in patients with AS. A PGA of around 1.5 indicates disease activity.

Effect of integrated Ayurvedic approach for management of ankylosing spondylitis: A case report

Abstract Ankylosing spondylitis (AS) is a seronegative spondyloarthropathy that mainly affects the spine and further involves various sacroiliac joints and articular structures. Human leukocyte antigen-B27 and tumor necrosis factor are said to be contributing factors. In this context, the etiology of the disease might be unknown or unclear. To date, conventional medicine has not provided a satisfactory treatment for this condition, but integrated Ayurveda regimens, such as oral medications, Panchakarma therapies, Yoga, and diet, could be beneficial for these manifestations and aimed at enhancing an individual’s quality of life. Ayurveda regimen, such as oral medications, Panchakarma therapies, Yoga, and diet, could benefit in this symptomatic presentation. A 27-year-old female presented with complaints of progressive neck pain and sacroiliac pain along with stiffness of the spine and hip for 6 years, associated with restricted movement of the spine. The condition was diagnosed as AS and treated for 6 months with Ayurveda treatment, Yoga, and diet. This therapeutic protocol was directed toward alleviating symptoms, reducing severe disability, and improving quality of life. The patient’s condition was assessed for symptoms of Asthimajjagata Vata, Ankylosing Spondylitis Quality of Life Scale score, and AS Disease Activity Score showed substantial improvement. After a 1-year follow-up in September 2022, C-reactive protein and erythrocyte sedimentation rate levels were within the normal range, and no subjective or objective symptoms were observed. This case study shows that cases of AS can be successfully managed with Ayurveda treatment.

ROLE OF URIC ACID IN CLINICAL MANIFESTATIONS OF ANKYLOSING SPONDYLITIS

Prevalence of ankylosing spondylitis (AS) is about 0.2–0.8% and increasing during last decades in Russia. Coronary Heart Disease (CHD) plays an important role in mortality in patients with rheumatic diseases. AS mainly affects able-bodied age persons thus having a significant social and economic impact. There plenty of biomarkers of AS, including those for early diagnosis. Purpose. To study the level of uric acid (UA) in patients with AS and its role in development of AS. Materials and methods. A total of 72 medical charts of patients hospitalized at Smolensk Regional Rheumatological Center were evaluated, among them 73.6% were men and 26.4% – women. AS was diagnosed according to classification criteria. Lab tests were done in a central lab using standard methodology. All data collected for each patient was entered into an Excel spreadsheet and analyzed. Results. Average patients age was 49.6±12.4 years. BMI was 28.1±5.4 kg/m2. Arterial Hypertension (AH) and CHD was diagnosed in 44.4% of patients. Glomerular Filtration Rate (GFR) was 95.1±21.9 mL/min. UA concentration were equal to 301.3±94.3 mmol/L, total cholesterol (TC) – 5.0±1.0 mmol/L, CRP – 60.5±35.1 IU/L. A direct correlation between CRP and BMI was revealed (p&lt;0.005). UA concentration in patients with AS and CHD was 347.3±73.9 mmol/L, while in patients with AS without CHD it was significantly lower: 261.8±77.4 mmol/L (p&lt;0,001). UA concentration in patients with AS and HLA-B27(+) was 345.1±90.8 mmol/L, in patients with AS and HLA-B27(-) – 259.1±75.1 mmol/L (p&lt;0,001). BASDAI in patients with AS was equal to 5.7±2.1. UA concentration in patients with mild to moderate AS was 255.4±77.7 mmol/L; severe AS – 343.4±75.3 mmol/L (p&lt;0.001). Correlations between TC level and BASDAI (p&lt;0.05) as well as between UA level and BASDAI (p&lt;0.05) were revealed. Conclusion. In patients with AS increased level of UA supports inflammation activity, forces subjective symptoms of the disease (pain), correlates with disease activity and BASDAI. Hyperuricemia increases risk of CHD, worsens prognosis of AS. UA may be considered as a biomarker of disease activity and prognosis of AS, atherosclerosis and cardiovascular diseases

Pan-immune inflammation value as a biomarker in ankylosing spondilitis and associated with disease activity

Aims: Ankylosing spondylitis(AS) is the most common and characteristic form of Spondyloarthritis. The pan-immune inflammation value(PIV) is a marker obtained from complete blood count parameters, which has been used as an inflammatory and immune marker. In this study, we aimed to investigate the relationship between inflammation and disease activity in patients with AS and PIV. Methods: In this prospective controlled study a total of 208 participants were included, consisting of 104 AS patients and 104 healthy controls. Complete blood count values, including neutrophils, monocytes, lymphocytes, platelets, and also C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), were measured in all participants. In AS group disease activity was assessed with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The AS group was divided into two subgroups based on BASDAI score: low disease activity(BASDAI score &amp;lt;4) and high disease activity(BASDAI score ≥4).The pan-immune inflammation value of patients and the control group was calculated as neutrophil count × monocyte count × platelet count/lymphocyte count. Comparative analysis was performed between the two groups, and these values were also compared based on the BASDAI. Results: The AS group exhibited statistically higher values of CRP, monocytes, and PIV compared to the control group (p&amp;lt;0.001 for all). Patients with BASDAI≥4 had a statistically lower disease duration (p&amp;lt;0.001) and lymphocyte count (p:0.012) compared to those with BASDAI&amp;lt;4. Patients with BASDAI ≥ 4 had statistically higher values of CRP, ESR, neutrophils, platelets, and PIV compared to those with BASDAI&amp;lt;4 (p&amp;lt;0.001, p&amp;lt;0.001, p&amp;lt;0.001, p:0.008, p&amp;lt;0.001 respectively). Strong positive correlation was found between PIV and BASDAI (rho=0.790; p&amp;lt;0.001), moderate positive correlation with PIV and CRP (rho=0.467; p&amp;lt;0.001) and also positive correlation was found between PIV and ESR (rho=0.326; p&amp;lt;0.001). The specificity and sensitivity of PIV using a cutoff value of &amp;gt;309,2 were 80.0% and 86.0% respectively, for the active group. Conclusion: Since the parameters comprising PIV are obtained from a complete blood count, it provides an advantage for its use as a simple and cost-effective marker in ankylosing spondylitis patients. In our study, we demonstrated that PIV is sensitive and specific in differentiating disease activity in patients with ankylosing spondylitis from healthy individuals and associated with disease activity.

Decreased expression of NAT10 in peripheral blood mononuclear cells from new-onset ankylosing spondylitis and its clinical significance

BackgroundNAT10 is the firstly recognized RNA acetyltransferase that participates in multiple cellular biological processes and human disease. However, the role of N-acetyltransferase 10 (NAT10) in ankylosing spondylitis (AS) is still poorly elaborated.MethodsFifty-six patients with New-Onset AS, 52 healthy controls (HC), 20 patients with rheumatoid arthritis (RA) and 16 patients with systemic lupus erythematosus (SLE) were recruited from The First Afliated Hospital of Nanchang University, and their clinical characteristics were recorded. The expression level of NAT10 in peripheral blood mononuclear cell (PBMC) was examined using reverse transcription-quantitative PCR analysis. The correlations between the expression level of NAT10 in the New-Onset AS patients and disease activity of AS were examined, and receiver operating characteristic (ROC) curves were built to evaluate predictive value in AS. Univariate analysis and multivariate regression analysis were used to analyze the risk factors and construct predictive model.ResultsThe mRNA expressions of NAT10 in PBMC from new-onset AS patients were significantly low and there were negative correlation between mRNA NAT10 and ASDAS-CRP, BASDIA in new-onset AS patients. ROC analysis suggested that mRNA NAT10 has value in distinguishing new-onset AS patients from HC, RA and SLE. Furthermore, a novel predictive model based on mRNA NAT10 and neutrophil percentages (N%) was constructed for distinguishing new-onset AS patients from HC (AUC = 0.880, sensitivity = 84.62%, specificity = 76.92%) and the predictive model correlated with the activity of new-onset AS. Furthermore, the predictive model could distinguish new-onset AS patients from RA and SLE (AUC = 0.661, sensitivity = 90.38%, specificity = 47.22%). Moreover, the potential predictive value of the combination of predictive model-HLA-B27 for AS vs. HC with a sensitivity of 92.86% (39/42), a specificity of 100.00% (52/52) and an accuracy of 96.81% (91/94) was superior to that of HLA-B27, which in turn had a sensitivity of 84.44% (38/45), a specificity of 100.00% (52/52) and an accuracy of 92.78% (90/97).ConclusionThe present study suggested that the decreased mRNA NAT10 may play a role in AS pathogenesis and predictive model based on mRNA NAT10 and N% act as bioindicator for forecast and progression of diseases.

Study of thyroid disorders in ankylosing spondylitis patients on anti-tumor necrosis factor treatment

Abstract: BACKGROUND: Ankylosing spondylitis (AS) is a systemic rheumatic disease characterized mainly by involvement of sacroiliac joints and axial skeleton. Tumor necrosis factor-alpha (TNF-α) inhibitors are biologic agents which are Food and Drug Administration approved to treat AS and also act as a key factor in the treatment of autoimmune thyroid disease. OBJECTIVE: This study aimed to evaluate the thyroid gland disorders (functions and thyroid autoantibodies) in AS patients on anti-TNF-α biologics and their relation to disease activity. PATIENTS AND METHODS: This comparative cross-sectional study included 75 AS patients classified into two groups: Group I: treated with NSAIDs (n = 30) and Group II: treated with anti-TNF-α biologics (n = 45). Thyroid function tests, thyroid autoantibodies, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and human leukocytic antigen B27 were measured. AS disease activity was assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Bath Ankylosing Spondylitis Metrology Index (BASMI) scores. Thyroid ultrasonography was used to detect any thyroid gland nodularity and echogenicity. RESULTS: There were significant differences between both groups regarding BASDAI (P = 0.005), CRP (P = 0.005), thyroid-stimulating hormone (TSH) (P = 0.001), and anti-thyroid peroxidase (anti-TPO) (P = 0.007). A significant difference was found regarding the thyroid status, with more normal thyroid and more hyperthyroid patients in the anti-TNF-treated group (P = 0.003). There were statistically significant positive correlations between BASDAI and CRP (P = 0.007), TSH (P = 0.004), and thyroid anti-TPO antibody (P = 0.008) in the anti-TNF-treated patients. By ultrasound examination of the thyroid gland, 75.6% of the anti-TNF group had normal thyroid gland compared to 56.6% of the other group, and the reported nodules were mostly of benign TIRADS classification. Comparing different subgroups of thyroid nodularity with different treatment regimens revealed significant differences in BASDAI and different laboratory investigations in favor of the anti-TNF-treated patients. CONCLUSION: From this cohort study, we can conclude that thyroid autoimmune disease and thyroid nodules in AS patients can be controlled by treatment with anti-TNF-α biologic drugs better than NSAIDs alone.

Ayurvedic management of Ankylosing Spondylitis (Kati prishtha trika graha): A case report

Ankylosing Spondylitis (AS) is a chronic systemic inflammatory disease affecting the axial (sacroiliac and spinal), girdle (hip and shoulder), peripheral joints, and the entheseal sites (such as heel, ankles, and patellar region). The condition manifests in chronic inflammatory back pain. As the disease progresses, patients develop a loss of flexibility due to spinal fusion. Considering the clinical features, the condition can be correlated with Kati prishtha trika graha in Ayurveda. This study presents a case of a 28-year-old male, who started with gradually progressing low backache with spinal stiffness for the last ten years, kyphosis, and morning stiffness (&gt;30 min). The patient was admitted to the hospital for management. Panchakarma (~five internal bio-cleansing therapies) procedures including Ruksha churna pinda swedana (~dry fomentation), Snehapana (~internal oleation), Virechana (~therapeutic purgation), Kala basti (~course of 16 therapeutic enemas), Snigdha churna pinda swedana (~bolus fomentation with oil), and Kati prishtha greeva basti (~therapeutic retention of oil over vertebral column) were adopted strategically along with Shamana chikitsa (~palliative management). The assessment was made using Bath AS Metrology Index, Bath AS Functional Index, and Bath AS Disease Activity Index. Encouraging results in the management of pain, stiffness, and spinal mobility were observed with the treatment, while no adversities were noticed during the treatment period.

Correlation of serum IL-6, TNF-α levels and disease activity in patients with ankylosing spondylitis.

The aim of this study was to investigate the serum interleukin (IL)-6 and tumor necrosis factor-alpha (TNF-α) levels in patients with ankylosing spondylitis (AS), and the correlation between serum levels and disease activity. ELISA was used to detect the serum TNF-α and IL-6 levels of AS patients (n=40) and normal controls (n=40) who were hospitalized or outpatient-diagnosed from June 2021 to May 2023. C-reactive protein (CRP) was detected by immune-enhanced turbidimetry. The erythrocyte sedimentation rate was determined by Wei's manual method. The correlation was analyzed by Pearson's correlation analysis. The levels of TNF-α and IL-6 in the AS group were significantly higher than those in the control group, and the levels of TNF-α and IL-6 in AS patients in the active phase were higher than those in the stable phase (p<0.05). CRP level was positively correlated with TNF-α, and IL-6 (r=0.02886 and 0.0273, p<0.05). Erythrocyte sedimentation rate (ESR) level was also positively correlated with TNF-α, and IL-6 (r=0.07568 and 0.0613, p<0.05). Serum TNF-α and IL-6 levels are correlated with AS disease activity, suggesting that they may be involved in the inflammatory response of AS.

Evaluating the inhibition of IL-17A and TNFα in a cartilage explant model cultured with Th17-derived cytokines

IntroductionT-helper 17 (Th17) cells produce IL-17A playing a critical role in activating the pathogenic chain leading to joint tissue inflammation and destruction. Elevated levels of Th17 cells and IL-17A have been detected in skin lesions, blood, and synovial fluid from patients with psoriatic arthritis (PsA) and ankylosing spondylitis (AS). Moreover, IL-17A inhibitors suppress disease activity in psoriasis, PsA and AS, supporting the evidence of IL-17A contributing to the disease pathogenesis. Although, IL-17A inhibitors are widely approved, it remains unclear how the inhibitory effect of IL-17A alters the extracellular matrix (ECM) of the joint in a Th17-conditioned inflammatory milieu. Therefore, the aim of this study was to establish a cartilage model cultured with conditioned medium from Th17 cells and inhibitors to explore the effect of IL-17A inhibition on joint tissue remodeling. MethodsNaïve CD4+ T cells from healthy human buffy coat were differentiated into Th17 cells, followed by Th17 cell activation to secrete Th17-related cytokines and molecules into media. The activated Th17 cells were isolated from the conditioned media (CM) and analyzed using flow cytometry to verify Th17 cell differentiation. The CM were assessed with ELISA to quantify the concentrations of cytokines secreted into the media by the Th17 cells. Healthy bovine cartilage explants were cultured with the Th17-CM and treated with IL-17A and TNFα inhibitors for 21 days. In harvested supernatant from the cartilage cultures, MMP- and ADAMTS-mediated biomarker fragments of type II collagen, aggrecan, and fibronectin were measured by ELISA to investigate the ECM remodeling within the cartilage tissue. ResultsTh17-CM stimulated a catabolic response in the cartilage. Markers of type II collagen and aggrecan degradation were upregulated, while anabolic marker of type II collagen formation remained on similar levels as the untreated explants. The addition of IL-17A inhibitor to Th17-CM decreased the elevated type II collagen and aggrecan degradation, however, degenerative levels were still elevated compared to untreated group. The addition of TNFα inhibitor completely reduced both type II collagen and aggrecan degradation compared to untreated explants. Moreover, the TNFα inhibitor treatment did not alter the type II collagen formation compared to untreated group. ConclusionThis study suggests that inhibition of IL-17A in Th17-conditioned cartilage tissue only partially reduced the MMP-mediated type II collagen degradation and ADAMTS-mediated aggrecan degradation, while the TNFα inhibitor treatment fully reduced both MMP- and ADAMTS-mediated ECM degradation. This exploratory study where ECM biomarkers are combined with Th17-conditioned ex vivo model may hold great potential as output for describing joint disease mechanisms and predicting structural effects of treatment on joint tissue.

Serum interα-trypsin inhibitor heavy chain H4 may be an anti-inflammatory marker reflecting disease risk, activity and treatment outcome of ankylosing spondylitis

Interα-trypsin inhibitor heavy chain H4 (ITIH4) modulates inflammation and immunity, which take part in the pathogenesis of ankylosing spondylitis (AS). The current research intended to discover the clinical value of serum ITIH4 quantification for AS management. Serum ITIH4 among 80 AS patients before current treatment initiation (baseline) at weeks (W) 4, 8 and 12 after treatment was detected by ELISA. Serum ITIH4 from 20 disease controls (DCs) and 20 healthy controls (HCs) was detected. ITIH4 expression was lower in AS patients than in DCs (p = 0.002) and HCs (p < 0.001). Among AS patients, ITIH4 was negatively associated with C-reactive protein (CRP) (r = −0.311, p = 0.005), bath AS disease activity index (BASDAI) (r = −0.223, p = 0.047), total pack pain (r = −0.273, p = 0.014) and AS disease activity score (ASDAS) (CRP) (r = −0.265, p = 0.018). Meanwhile, ITIH4 was negatively related to tumor necrosis factor (TNF)-α (r = −0.364, p = 0.001), interleukin (IL)-1β (r = −0.251, p = 0.025), IL-6 (r = −0.292, p = 0.009) and IL-17A (r = −0.254, p = 0.023). After treatment, the assessment of the spondylitis arthritis international society 40 response rate was 28.7% at W4, 46.3% at W8 and 55.0% at W12; ITIH4 showed an increasing trend from baseline to W12 (p < 0.001). Furthermore, ITIH4 at W8 (p = 0.020) and W12 (p = 0.035), but not at baseline or W4 (both p > 0.05), was enhanced in response patients vs. nonresponse patients. Additionally, ITIH4 at W12 was increased in AS patients receiving TNF inhibitors vs. those receiving nonsteroidal anti-inflammatory drugs (NSAIDs) (p = 0.024). Serum ITIH4 increases after treatment, and its augmentation is correlated with lower disease activity, decreased inflammation and enhanced treatment response in AS patients.

Influence of Manual Therapy and Stretching Exercises on Mobility Status and Pulmonary Function Tests Among Patients with Ankylosing Spondylitis

Introduction: AS (ankylosing spondylitis) is a systemic disease that impairs entire body functioning of a patient. The most common dysfunctions concern the area of the chest, spine and upper limb. As a consequence of these dysfunctions, the lungs of patients work in abnormal conditions, impairing their functioning.Objectives: The aim of the study is assessing the impact of rehabilitation among patients with AS on functional and respiratory parameters.Material and methods: The study comprised 45 patients divided into two groups. For 25 patients in the group rehabilitation was focused on manual therapy (TM) while 20 patients were rehabilitated on the basis of stretching exercises (SE). As part of improvement progress assessment, the following were measured: upper limb mobility, chest expansion, Occiput to Wall Distance test, spinal angle, functional examination of the respiratory system, the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI) and Pain Disability Index (PDI) questionnaires.Results: After rehabilitation, the Occiput to Wall Distance test also improved expansion of the chest. The BASDAI, BASFI, questionnaires and the VAS scale improved in both study groups. Among respiratory parameters, inspiratory and respiratory muscle strength further increased.Conclusions: Rehabilitation is a very effective form of improving the patient's functional status and should be an indispensable element of the patient's treatment. Both manual therapy and stretching exercises have been shown to be successful.

HLA B27-positive ankylosing spondylitis professional soccer player with a successful return to sports

Ankylosing spondylitis (AS) is a disease of young adulthood and without adequate treatment it dramatically reduces physical activity. To present a case with AS that successfully returned to professionally playing sports after treatment. A 19-year-old Eastern European Russian professional male soccer player with AS complained of right ankle joint pain not related to any trauma or injury and gradually intensified. The player's regular medical tests during the preceding years and were unremarkable. He would occasionally complain of discomfort in the ankle joints, sacroiliac area and symphysis but did not limit his regular training activity. He received the standard treatment of sports injuries that included: 14 days of limited physical activity, ibuprofen 200 mg twice/day, cryotherapy and joint taping. Examination revealed mobile joints, regular in shape without any swelling. Erythrocyte sedimentation rate (ESR) was 60 mm/1st hr and C-reactive protein (CRP) 50 mg/dl. AS was diagnosed as he fulfilled the classification criteria. HLA-B27 was positive, left sacroiliitis was present on magnetic resonance imaging (MRI). The Bath AS disease activity index (BASDAI) was 5.9. Treatment also included golimumab 50 mg/month. He improved, returned to regular training and continued playing sports professionally amid supportive therapy. The last BASDAI was 1.5. AS patients with initially high levels of physical activity may restore professionally playing of sports when a proper management plan is provided. Further monitoring is warranted and the creation of a database for athletes with rheumatic diseases is recommended in order to standardize treatment protocols.

Ankilozan Spondilitte Hastalık Aktivitesi ve Obezitenin Kinezyofobi Üzerindeki Etkisi

Objective: This study aims to determine the rate of kinesiophobia in ankylosing spondylitis (AS) patients and to determine the relationship between kinesiophobia and disease activity, obesity, quality of life, functional status, fatigue, and fear of falling. Methods: The study design is a prospective study. That included 83 ankylosing spondylitis patients and 79 age- and gender-matched healthy controls. Kinesiophobia was evaluated using the Tampa Scale for Kinesiophobia (TSK), disease activity with the Bath AS Disease Activity Index (BASDAI), functional status with the Health Assessment Questionnaire (HAQ) and Bath AS Functional Index (BASFI), fear of falling with the Falls Efficacy Scale International (FES-I) and Fatigue Severity Scale (FSS), Quality of Life Questionnaire (ASQoL), Body Mass Index (BMI). The correlation of outcome measures with kinesiophobia levels was analyzed, and all parameters were compared in patients with (TSK&amp;gt;37) and without kinesiophobia (TSK≤37). Results: In AS patients, the rate of kinesiophobia was 78.3%, the mean TSK score was 43.85±9.78, while in healthy controls, the kinesiophobia rate was 17.7%, the mean TSK score was 27.07±8.46 (odds ratio (OR)=16.766, 95% confidence interval (CI): 7.697-36.518; p&amp;lt;0.001). TSK was positively correlated with BMI, ASQoL, BASDAI, HAQ, FES-I, FSS, and BASFI (r=0.336, r=0.457, r=0.341, r=0.447, r=0.269, r=0.371, p&amp;lt;0.05 for each). Patients with a BMI&amp;gt;25, and a BASDAI&amp;gt; 4 had higher TSK scores (p=0.041 and p&amp;lt;0.001, respectively). Conclusion: AS patients have a very high rate of kinesiophobia. Patients with obesity and high disease activity have higher levels of kinesiophobia. Detection of kinesiophobia in patients with AS, control of weight/obesity, and reduction of disease activity should be an important goal.