Biological treatment usage in patients with HIV and rheumatic disease, 2003-2021: long-term safety and follow-up.

OBJECTIVE: This study examined the safety and efficacy of biological agents, especially tumour necrosis factor (TNF) inhibitors, for HIV-positive rheumatology patients refractory to standard therapy. METHODS: This study is a retrospective case series including patients derived from a community HIV clinic as well as from two academic centres. Initial visit data collected included: sociodemographic characteristics, CD4 counts, HIV viral load and medication use. Patients with persistent disease activity despite standard conservative therapy were begun on biological agents.The main outcomes were patient and physician global assessment of treatment response and medication side effects in patients with rheumatological disorders treated with biological medications over time. RESULTS: Seventeen patients were seen from 2003 to 2021, including eight from our previous cohort published in 2008 and nine seen since then, five of whom taking TNF blockers for more than 10 years. Three (17.7%) had rheumatoid arthritis, five (29.4%) psoriatic arthritis, four (23.5%) axial spondyloarthritis and the rest (29.4%) peripheral spondyloarthritis. Antiretroviral therapy had been used in 15. All but one had at least a partial response to biological therapy. There were no major infectious episodes necessitating the discontinuation of medications with only one patient discontinuing treatment due to rising HIV viral load. Patients not on antiretroviral therapy reported no adverse side effects from biological therapy. Four patients were switched to ustekinumab, secukinumab, tocilizumab or upadacitinib from anti-TNF therapy without complications. CONCLUSIONS: These data suggest that biological therapy, especially anti-TNF agents are safe and well tolerated in HIV positive individuals even over several years.

Spinal Radiographic Progression and Predictors of Progression in Patients With Radiographic Axial Spondyloarthritis Receiving Ixekizumab Over 2 Years.

OBJECTIVE: To evaluate the long-term effect of ixekizumab (IXE) on radiographic changes in the spine in patients with radiographic axial spondyloarthritis (r-axSpA) by measuring change from baseline through 2 years in modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), and to identify potential predictors of progression. METHODS: This study evaluates patients from COAST-V (ClinicalTrials.gov: NCT02696785, biologic disease-modifying antirheumatic drug-naïve) and COAST-W (NCT02696798, tumor necrosis factor inhibitor-experienced) who had mSASSS data at baseline in the originating studies and 108 weeks after baseline in the extension study COAST-Y (NCT03129100). We examined the proportion of patients who did not have spinal radiographic progression through 2 years (108 weeks) of treatment with IXE (80 mg every 2 or 4 weeks) and the change from baseline to year 2 in mSASSS. Potential predictors of spinal radiographic progression were also evaluated. RESULTS: Among patients with evaluable radiographs who were originally assigned to IXE (n = 230), mean (SD) change in mSASSS from baseline at year 2 was 0.3 (1.8). The proportion of nonprogressors over 2 years was 89.6% if defined as mSASSS change from baseline < 2 and 75.7% if defined as mSASSS change from baseline ≤ 0. Predictors of structural progression at year 2 (mSASSS change > 0) were age ≥ 40, baseline syndesmophytes, HLA-B27 positivity, and male sex. Week 52 inflammation in Spondyloarthritis Research Consortium of Canada spine was also a predictor of radiographic progression at year 2 in patients with magnetic resonance imaging data in COAST-V (n = 109). CONCLUSION: The majority of patients with r-axSpA receiving IXE had no radiographic progression in the spine through 2 years of treatment. Predictors were generally consistent with previous studies.

The Association of Tumor Necrosis Factor Inhibitor Use With Incident Hypertension in Ankylosing Spondylitis: Data From the PSOAS Cohort.

OBJECTIVE: Individuals with ankylosing spondylitis (AS) have a greater cardiovascular (CV) risk than those in the general population. The effect of tumor necrosis factor inhibitors (TNFis) on CV risk, including on the development of hypertension (HTN), remains unclear, with some data suggesting higher risk. We assessed the association of TNFi use with incident HTN in a longitudinal AS cohort. METHODS: Adults with AS enrolled in a prospective cohort in 2002-2018 were examined every 4-6 months. TNFi use during the preceding 6 months was ascertained at each study visit. We defined HTN by patient-reported HTN, antihypertensive medication use, or, on 2 consecutive visits, systolic blood pressure (BP) ≥ 140 mmHg or diastolic BP ≥ 90 mmHg. We evaluated the association between TNFi use and the development of HTN with marginal structural models, estimated by inverse probability-of-treatment weighting, to account for time-dependent confounders and informative censoring. Potential confounders included age, sex, race, site, nonsteroidal antiinflammatory drug use, and disease activity. RESULTS: We included 630 patients without baseline HTN and with at least 1 year of follow-up. Of these, 72% were male, mean age was 39 ± 13 years, and 43% used TNFi at baseline. On follow-up (median 5 yrs), 129 developed incident HTN and 163 started on TNFi during follow-up. TNFi use was not associated with incident HTN (adjusted HR 1.10, 95% CI 0.83-1.37). CONCLUSION: In our prospective AS cohort, TNFi use was not significantly associated with incident HTN.

Identifying trajectories of radiographic spinal disease in ankylosing spondylitis: a 15-year follow-up study of the PSOAS cohort.

OBJECTIVES: Little is known with certainty about the natural history of spinal disease progression in ankylosing spondylitis (AS). Our objective was to discover if there were distinct patterns of change in vertebral involvement over time and to study associated clinical factors. METHODS: Data were analysed from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) observational cohort. All patients met modified New York Criteria for AS and had ≥2 sets of radiographs scored by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) by two independent readers between 2002 and 2017. Group-based trajectory modelling (GBTM) was used to classify patients into distinct groups of longitudinal mSASSS considering sociodemographic and clinical covariables. The optimal trajectory model and number of trajectories was selected using Nagin's Bayesian information criterion (BIC). RESULTS: A total of 561 patients with 1618 radiographs were analysed. The optimum number of trajectory groups identified was four (BIC -4062). These groups were subsequently categorized as: non-progressors (204 patients), late-progressors (147 patients), early-progressors (107 patients) and rapid-progressors (103 patients). Baseline predictors associated with higher spinal disease burden groups included: baseline mSASSS, male gender, longer disease duration, elevated CRP and smoking history. In addition, time-varying anti-TNF use per year was associated with decreased mSASSS progression only in the rapid-progressor group. CONCLUSIONS: GBTM identified four distinct patterns of spinal disease progression in the PSOAS cohort. Male gender, longer disease duration, elevated CRP and smoking were associated with higher spinal disease groups. Independent confirmation in other AS cohorts is needed to confirm these radiographic patterns.

Cardiovascular Risk Scores in Axial Spondyloarthritis Versus the General Population: A Cross-sectional Study.

OBJECTIVE: Cardiovascular (CV) morbidity and mortality are increased in axial spondyloarthritis (axSpA).We conducted a cross-sectional study evaluating the 10-year atherosclerotic cardiovascular disease (ASCVD) risk in axSpA compared to the general US population. METHODS: We included 211 adults, 40-75 years old with ankylosing spondylitis (AS) or nonradiographic axSpA from 2 sites, who had available data on comorbidities, medication use, blood pressure measures, and laboratory cholesterol values. General population comparators from the 2009-2014 National Health and Examination Survey (NHANES) cycles were matched 4:1 to subjects, on age, sex, and race. We estimated the prevalence ratio for a 10-year ASCVD risk score ≥ 7.5% comparing axSpA and matched NHANES comparators using conditional Poisson regression. RESULTS: Overall, subjects were 53.9 ± 11.2 years old, 69% were male, and 74% were White. The mean 10-year ASCVD risk score was 6.7 ± 6.9% for those with axSpA, and 9.0 ± 10.5% for NHANES comparators. Compared to those with axSpA, the prevalence of current smoking and diabetes was higher among NHANES comparators. The estimated prevalence ratio for a 10-year ASCVD risk score ≥ 7.5% comparing those with axSpA and their age-, sex-, and race-matched comparators was 0.96 (95% CI 0.74-1.24). CONCLUSION: The prevalence of a 10-year ASCVD risk score ≥ 7.5% was not significantly different comparing axSpA patients and those drawn from the general population who were similar in terms of age, sex, and race. Future studies should focus on improved CV risk prediction in axSpA, because underestimation by a general population risk score may potentially explain these results.

Effects of Intravenous Golimumab on Health-Related Quality of Life in Patients with Ankylosing Spondylitis: 28-Week Results of the GO-ALIVE Trial.

OBJECTIVE: Evaluate the effect of intravenous golimumab on health-related quality of life (HRQoL) in patients with ankylosing spondylitis (AS) through week 28 of the phase III, multicenter, randomized, double-blind, placebo-controlled GO-ALIVE study. METHODS: Adult patients (n = 208) were randomized to IV golimumab 2 mg/kg (n = 105) at weeks 0, 4, and 12 and every 8 weeks or placebo (n = 103) at weeks 0, 4, and 12, with crossover to golimumab 2mg/kg at weeks 16, 20, and every 8 weeks. General HRQoL was evaluated using the Short Form Health Survey (SF-36) Physical Component Summary/Mental Component Summary (PCS/MCS), and the EQ VAS, and AS disease-specific HRQoL was assessed using the Ankylosing Spondylitis Quality of Life (ASQoL) instrument. RESULTS: Mean improvements from baseline in SF-36 PCS were greater in the golimumab group versus the placebo group at weeks 8 and 16 (6.8 vs 2.1 and 8.5 vs 2.9, respectively; P < .001); similar results were observed for SF-36 MCS (5.6 vs 1.7 and 6.5 vs 0.8, respectively; P < .001). Mean improvement in each of 8 subscale scores of the SF-36 were also greater for golimumab-treated patients versus placebo at weeks 8 and 16. Mean improvements in EQ VAS and ASQoL were greater in the golimumab group versus placebo at week 8 and week 16. Greater proportions of golimumab-treated patients had clinically meaningful improvement in SF-36 PCS, SF-36 MCS, EQ VAS, and ASQoL at weeks 8 and 16; improvements in SF-36 PCS/MCS, EQ VAS, and ASQoL were maintained through week 28. CONCLUSIONS: Golimumab-treated patients had greater mean improvements in HRQoL measures compared with placebo through week 16. Clinically meaningful improvements were observed as early as week 8 and continued through week 28.

The changing profile of ankylosing spondylitis in the biologic era.

OBJECTIVE: To compare disease characteristics, comorbidities, and medication utilization of 1141 patients with ankylosing spondylitis (AS) with short (< 20 years) and long (≥ 20 years) disease duration enrolled in the Prospective Study of Outcomes in AS (PSOAS) study over three different periods of time and followed longitudinally. METHODS: Study visits were carried out every 6 months examining disease activity (Bath AS Disease Activity Index (BASDAI), C-reactive protein, erythrocyte sedimentation rate), functional impairment, depression, and medication utilization as well as radiographic severity. Groups were compared with regression models using generalized estimating equation, linear, and Poisson regressions after adjusting for sites and for patients withdrawing from the study at less than 2 years follow-up. RESULTS: Overall, AS patients with long disease duration were more likely to be married, white, receiving disability, and to be with higher functional impairment and radiographic severity, more uveitis, diabetes, hypertension, cardiovascular disease, and osteoporosis, and with less nonsteroidal anti-inflammatory drug (NSAID) and more opioid use than those with short disease duration. Current smoking decreased between 2002 and 2019 regardless of disease duration. Lower baseline NSAID and methotrexate/sulfasalazine use and higher TNF inhibitor usage were seen only in those with shorter disease duration, though NSAID use and functional impairment decreased over time in both groups. Disease activity, depression scores, and NSAID use decreased and anti-TNF use increased in those followed > 8 years. CONCLUSIONS: Patients with AS enrolling in this multicenter longitudinal cohort have different disease profiles and medication utilization over time, perhaps reflecting innovations in treatment and increasing disease awareness. Key Points • The use of NSAIDs, nonbiologic DMARDs, and prednisone has decreased over the past 16 years in patients with AS. • The use of anti-TNF agents has dramatically increased. • In treated patients, disease activity, depression scores, and functional impairment have decreased over time.

The IgG galactosylation ratio is higher in spondyloarthritis patients and associated with the MRI score.

OBJECTIVES: MRI is an important tool for evaluating inflammation levels and assessing treatment response in patients with ankylosing spondylitis (AS). However, it is expensive and requires experienced physicians. The goal of this study was to identify a biomarker correlated with the MRI score. METHODS: A total of 558 spondyloarthritis (SpA) patients including 527 AS patients, 10 psoriasis (PsA) patients, and 21 non-radiographic SpA (nr-SpA) patients and 725 controls were enrolled for the studies. Plasma IgG galactosylation (IgG-Gal) level was measured by mass spectrometry. Clinical indexes such as Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and C-reactive protein (CRP) were measured in all AS patients. MRIs and X-rays were obtained from 65 AS patients who were followed up for 6 months. RESULTS: The IgG-Gal ratio was twice as high in the AS patients compared with the controls. It correlated with inflammation indices which is evaluated by MRI according to SPARCC. (Pearson coefficient/p value was 0.6/7E10-6). In addition, AS patients with a higher IgG-Gal ratio at baseline tended to show greater improvement in inflammation scores by MRI both in 3-month follow-up and 6-month follow-up. CONCLUSION: The IgG-Gal ratio was significantly increased in AS patients. In clinical care, it may be used as a potential biomarker for diagnosis in the future. Key Points • IgG galactosylation level was abnormal in SpA patients. • IgG galactosylation level was associated with MRI indices.

Longitudinal associations between depressive symptoms and clinical factors in ankylosing spondylitis patients: analysis from an observational cohort.

OBJECTIVES: Although cross-sectional studies have shown that ankylosing spondylitis-specific factors correlate with depressive symptom severity, the association of these factors over time is unresolved. We examined the demographic and clinical factors associated with longitudinal depressive symptom severity in AS patients. METHODS: We analyzed sociodemographic, clinical, behavioral and medication data from 991 patients from the Prospective Study of Outcomes in Ankylosing spondylitis cohort, and measured depression severity with the Center for Epidemiological Studies Depression (CES-D) Scale administered at approximately 6-month visit intervals. Multivariable longitudinal negative binomial regression models were conducted using generalized estimating equation modeling to assess the demographic, clinical, and medication-related factors associated with depression severity by CES-D scores over time. RESULTS: The median baseline CES-D score (possible range 0-60) was 10.0 (interquartile range = 5, 17). In longitudinal multivariable analyses, higher CES-D scores were associated with longitudinal smoking, greater functional impairment, greater disease activity, self-reported depression, and poor global health scores. Marital status (e.g., being married) was associated with lower CES-D. Adjusted mean CES-D scores in our model decreased over time, with a significant interaction between time and gender observed. CONCLUSION: This study identified longitudinal clinical factors such as greater disease activity, greater functional impairment, and poor global health to be associated with longitudinal depression severity. These factors are potentially modifiable and may help manage depressive symptoms in AS.

IgG Galactosylation status combined with MYOM2-rs2294066 precisely predicts anti-TNF response in ankylosing spondylitis.

BACKGROUND: Tumor necrosis factor (TNF) blockers have a high efficacy in treating Ankylosing Spondylitis (AS), yet up to 40% of AS patients show poor or even no response to this treatment. In this paper, we aim to build an approach to predict the response prior to clinical treatment. METHODS: AS patients during the active progression were included and treated with TNF blocker for 3 months. Patients who do not fulfill ASASAS40 were considered as poor responders. The Immunoglobulin G galactosylation (IgG-Gal) ratio representing the quantity of IgG galactosylation was calculated and candidate single nucleotide polymorphisms (SNPs) in patients treated with etanercept was obtained. Machine-learning models and cross-validation were conducted to predict responsiveness. RESULTS: Both IgG-Gal ratio at each time point and differential IgG-Gal ratios between week 0 and weeks 2, 4, 8, 12 showed significant difference between responders and poor-responders. Area under curve (AUC) of the IgG-Gal ratio prediction model was 0.8 after cross-validation, significantly higher than current clinical indexes (C-reactive protein (CRP) = 0.65, erythrocyte sedimentation rate (ESR) = 0.59). The SNP MYOM2-rs2294066 was found to be significantly associated with responsiveness of etanercept treatment. A three-stage approach consisting of baseline IgG-Gal ratio, differential IgG-Gal ratio in 2 weeks, and rs2294066 genotype demonstrated the ability to precisely predict the response of anti-TNF therapy (100% for poor-responders, 98% for responders). CONCLUSIONS: Combination of different omics can more precisely to predict the response of TNF blocker and it is potential to be applied clinically in the future.

Safety and Efficacy of Intravenous Golimumab in Adults with Ankylosing Spondylitis: Results through 1 Year of the GO-ALIVE Study.

OBJECTIVE: Evaluate safety and efficacy of intravenous (IV) golimumab (GOL) in patients with active ankylosing spondylitis (AS) through 1 year. METHODS: A total of 208 patients were randomized to IV infusions of GOL 2 mg/kg (n = 105) at weeks 0, 4, and every 8 weeks thereafter or placebo (n = 103) at weeks 0, 4, and 12, then crossover to GOL at weeks 16, 20, and every 8 weeks thereafter through Week 52. Efficacy was assessed using the Assessment of Spondyloarthritis international Society (ASAS) criteria, the Ankylosing Spondylitis Disease Activity Score (ASDAS), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the Bath Ankylosing Spondylitis Functional Index (BASFI). Health-related quality of life was assessed using the AS Quality of Life (ASQoL) index. Efficacy and safety were monitored through Week 52 and Week 60, respectively. RESULTS: The primary endpoint (ASAS20) and all controlled endpoints at Week 16 were achieved. At Week 52, 69.5% and 65.0% of patients in the GOL group and placebo crossover group, respectively, achieved an ASAS20; 56.2% and 51.5% achieved an ASAS40; 56.2% and 55.3% achieved a BASDAI50; 24.8% and 24.3% achieved ASAS partial remission; and 25.7% and 26.2% met ASDAS inactive disease criteria (all last observation carried forward). Mean changes from baseline to Week 52 in BASFI and ASQoL scores were similar between the GOL group and the placebo crossover group (BASFI: -2.7 and -2.6; ASQoL: -5.5 and -5.4). Through Week 60, 55.4% of all GOL-treated patients had ≥ 1 adverse events (AE); 3.4% had ≥ 1 serious AE. CONCLUSION: Efficacy was maintained through 1 year with IV GOL 2 mg/kg among patients with active AS. AE were consistent with the known safety profile of GOL.

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.

Smoking quantity determines disease activity and function in Chinese patients with ankylosing spondylitis.

The objective of this study was to systemically and comprehensively evaluate the associations between smoking and disease outcomes in patients with ankylosing spondylitis (AS). Information on smoking, clinical features, and sociodemographic characteristics was collected by a questionnaire administered directly to the patient. Group differences were analyzed by t test or chi-square test. Logistic regression analysis was conducted with the Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), C-reactive protein, and erythrocyte sedimentation rate as the dependent variables and different stratification of smoking duration, smoking intensity, and cumulative smoking as independent variables. In order to compare our results with previous studies, meta-analysis was performed to calculate standardized mean difference (SMD) for relationship between outcomes and smoking status. A total of 1178 AS patients were analyzed. Compared with non-smokers, the risk of having active disease (BASDAI ≥ 4) was higher in patients who smoked at least 15 years, or 15 cigarettes per day, or 15 pack-years (OR = 1.70 [1.06, 2.73], 1.75 [1.08, 2.82], and 1.97 [1.06, 3.67], respectively); and smokers had increasing risk of BASDAI ≥ 4 with increasing years of smoking, or cigarettes per day, or pack-years (p-trend = 0.010, 0.008 and 0.006, respectively). The risk of having active disease was higher in patients who smoked at least 15 cigarettes per day or 15 pack-years (OR = 1.74 [1.06, 2.84] and 2.89 [1.56, 5.35], respectively), with increasing number of cigarettes per day and pack-years. Smokers had an increased risk of BASFI ≥ 4 (p-trend = 0.040 and 0.007, respectively). By meta-analysis, current, former and ever smokers had significantly higher BASDAI (SMD = 0.34 [0.18, 0.48], 0.10 [0.01, 0.19], and 0.27 [0.20, 0.34], respectively) and BASFI (SMD = 0.35 [0.16, 0.55], 0.30 [0.22, 0.39], and 0.35 [0.21, 0.50], respectively) compared to non-smokers. Smoking is a risk factor for greater disease activity and worse functioning in AS patients.

Opioid Analgesic Use in Patients with Ankylosing Spondylitis: An Analysis of the Prospective Study of Outcomes in an Ankylosing Spondylitis Cohort.

OBJECTIVE: Opioid analgesics may be prescribed to ankylosing spondylitis (AS) patients with pain that is unresponsive to antirheumatic treatment. Our study assessed factors associated with opioid usage in AS. METHODS: A prospective cohort of 706 patients with AS meeting modified New York criteria followed at least 2 years underwent comprehensive clinical evaluation of disease activity and functional impairment. These were assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI). Radiographic severity was assessed by the Bath Ankylosing Spondylitis Radiology Index and modified Stokes Ankylosing Spondylitis Scoring System. Medications taken concurrently with opioids, as well as C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR), were determined at each study visit, performed every 6 months. Analyses were carried out at baseline, and longitudinal multivariable models were developed to identify factors independently associated with chronic and intermittent opioid usage over time. RESULTS: Factors significantly associated with opioid usage, especially chronic opioid use, included longer disease duration, smoking, lack of exercise, higher disease activity (BASDAI) and functional impairment (BASFI), depression, radiographic severity, and cardiovascular disease. Patients taking opioids were more likely to be using anxiolytic, hypnotic, antidepressant, and muscle relaxant medications. Multivariable analysis underscored the association with smoking, older age, antitumor necrosis factor agent use, and psychoactive drugs, as well as with subjective but not objective determinants of disease activity. CONCLUSION: Opioid usage was more likely to be associated with subjective measures (depression, BASDAI, BASFI) than objective measures (CRP, ESR), suggesting that pain in AS may derive from sources other than spinal inflammation alone.

Safety and Efficacy of Golimumab Administered Intravenously in Adults with Ankylosing Spondylitis: Results through Week 28 of the GO-ALIVE Study.

OBJECTIVE: To evaluate the safety and efficacy of intravenous golimumab (GOL) in patients with active ankylosing spondylitis (AS). METHODS: In a phase III, randomized, double-blind, placebo (PBO)-controlled trial, 208 patients were randomized (1:1) to intravenous (IV) infusions of GOL 2 mg/kg (n = 105) at weeks 0, 4, 12, and every 8 weeks, or PBO (n = 103) at weeks 0, 4, and 12, with crossover to GOL at Week 16. The primary endpoint was ≥ 20% improvement from baseline in the Assessment of Spondyloarthritis International Society Criteria (ASAS20) at Week 16. Secondary endpoints included ASAS40, ≥ 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI50), and change in the Bath Ankylosing Spondylitis Functional Index (BASFI) at Week 16. Safety was monitored through Week 28. RESULTS: Significantly greater proportions of GOL-treated patients had ASAS20 response at Week 2 (37.1% vs 19.4%; p = 0.005) and at Week 16 (73.3% vs 26.2%; p < 0.001). At Week 16, 41.0% of those receiving GOL achieved BASDAI50 compared with 14.6% of those taking PBO (p < 0.001), and the GOL group had greater mean improvement in BASFI (-2.4 vs -0.5; p < 0.001). Through Week 16, 23.3% of patients in the PBO group and 32.4% of patients in the GOL group had ≥ 1 adverse event (AE); infections being the commonest type of AE. Through Week 28, two GOL-treated patients had a serious AE. CONCLUSION: GOL 2 mg/kg administered IV at weeks 0, 4, and every 8 weeks significantly reduced the signs and symptoms of AS in adults. AE were consistent with other antitumor necrosis factor therapies, with no new safety signals (Clinicaltrials.gov: NCT02186873).

Ethnicity and disease severity in ankylosing spondylitis a cross-sectional analysis of three ethnic groups.

The purpose of this study is to compare disease severity in ankylosing spondylitis (AS) in three ethnic groups. We assessed 925 AS patients (57 Blacks, 805 Whites, 63 Latinos) enrolled in the longitudinal Prospective Study of Outcomes in AS (PSOAS) for functional impairment, disease activity, and radiographic severity. Comparisons of clinical characteristics and HLA-B27 frequency for each group were performed, in two multivariable regression models, we compared the baseline Bath Ankylosing Spondylitis Radiographic Index (BASRI) and modified Stokes Ankylosing Spondylitis Spine Score (mSASSS) by ethnicity, adjusting for covariates. Blacks had greater functional impairment (Bath Ankylosing Spondylitis Functional Index) (median 62.5 vs. 27.8 in Whites and 38.1 in Latinos; p < 0.0001); higher disease activity (Bath Ankylosing Spondylitis Disease Activity Index), (median 5.9 vs. 3.5 in Whites and 4.5 in Latinos; p < 0.0001), erythrocyte sedimentation rate (median 27.0 in Blacks vs. 10.0 in Whites and 17.0; p < 0.0001), and C-reactive protein levels (median 1.2 vs. 0.4 mg/dL in Whites and 0.9 in Latinos; p < 0.0001). Baseline BASRI and mSASSS were higher in Blacks (mean 9.5 and median 38.2, respectively) compared to Whites (7.3 and 6.4) and Latinos (7.3 and 8.1), (p = 0.004, 0.007), respectively, more significant as disease duration increased. HLA-B27 occurred in 62.5% of Blacks, 85.3% of Whites, and 86.7% of Latinos (p < 0.0001). On multivariable analysis, higher BASRI and mSASSS were associated with Black ethnicity, after adjusting for disease duration and gender as well as TNF inhibitor (TNFi) usage, smoking status, or education level. Blacks with AS have more severe disease compared to either Whites or Latinos.

CCL2 in the Circulation Predicts Long-Term Progression of Interstitial Lung Disease in Patients With Early Systemic Sclerosis: Data From Two Independent Cohorts.

OBJECTIVE: There are few clinical predictors of the progression of systemic sclerosis (SSc)-related interstitial lung disease (ILD). The purpose of this study was to examine the predictive significance of key cytokines for long-term progression of ILD and survival in 2 independent cohorts of patients with early SSc. METHODS: Plasma levels of 11 Th1/Th2 cytokines (interleukin-1ß [IL-1ß], IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, tumor necrosis factor, CCL2, interferon-inducible T cell α chemoattractant, and interferon-γ-inducible 10-kd protein) were measured in 266 patients with early SSc in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) discovery cohort. Levels of CCL2, IL-10, and IL-6 were measured in 171 patients with early SSc in the Canadian Scleroderma Research Group (CSRG) replication cohort. The primary outcome measure was a decline in the forced vital capacity percent predicted (FVC%) value over time. A joint analysis of longitudinal FVC% values and survival was performed. RESULTS: After adjustment for age, sex, and ethnicity, CCL2 and IL-10 were found to be significant predictors of ILD progression in the discovery cohort. Higher CCL2 levels predicted a faster decline in FVC% values (b = -0.57, P = 0.032), while higher IL-10 levels predicted a slower decline (b = 0.26, P = 0.01). A higher CCL2 value was also predictive of poorer survival (hazard ratio 1.76, P = 0.030). In the CSRG replication cohort, higher CCL2 levels predicted a faster decline in FVC% values (b = -0.58, P = 0.038), but neither IL-10 nor IL-6 had predictive significance. A higher CCL2 level also predicted poorer survival (hazard ratio 3.89, P = 0.037). CONCLUSION: Higher CCL2 levels in the circulation were predictive of ILD progression and poorer survival in patients with early SSc, findings that support the notion that CCL2 has a role as a biomarker and potential therapeutic target.