Efficacy and safety of Janus kinase inhibitors in axial spondyloarthritis.

Skin manifestations are common in axial spondyloarthritis (axSpA) and may precede axial involvement. Multidisciplinary management of patients with spondyloarthritis (SpA) is essential. Combined dermatology-rheumatology clinics are established for early recognition of the disease, comorbidities and a comprehensive treatment approach. Treatment options for axSpA are limited because conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids are ineffective for axial symptoms. Janus kinase inhibitors (JAKi) are targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) that decrease transduction signalling to the nucleus, resulting in a reduced inflammatory response. Currently, tofacitinib and upadacitinib are approved for treating axSpA in patients with inadequate response to TNF inhibitors (TNFi). Upadacitinib has shown efficacy in non-radiographic axSpA (nr-axSpA), suggesting that JAKi are efficacious across the spectrum of axSpA. The availability of JAKi has opened more options for patients with active axSpA based on the efficacy data and the ease of administration.

Responsiveness and Minimum Clinically Important Difference in Patient-Reported Outcome Measures Among Patients With Psoriatic Arthritis: A Prospective Cohort Study.

OBJECTIVE: To determine the responsiveness to therapy and minimum clinically important improvement (MCII) for patient-reported outcome measures in psoriatic arthritis (PsA) and to examine the impact of baseline disease activity on the ability to demonstrate change. METHODS: A longitudinal cohort study was performed within the PsA Research Consortium. Patients completed several patient-reported outcomes, including the Routine Assessment of Patient Index Data, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Psoriatic Arthritis Impact of Disease 12-item (PsAID12) questionnaire, and others. The mean change in the scores between visits and standardized response means (SRMs) were calculated. The MCII was calculated as the mean change in score among patients who reported minimal improvement. SRMs and MCIIs were compared among subgroups with moderate to highly active PsA and those with lower disease activity. RESULTS: Among 171 patients, 266 therapy courses were included. The mean ± SD age was 51 ± 13.8 years, 53% were female, and the mean swollen and tender joint counts were 3 and 6, respectively, at baseline. SRMs and MCII for all measures were small to moderate, although greater among those with higher baseline disease activity. BASDAI had the best SRM overall and for less active PsA, and the clinical Disease Activity of PsA (cDAPSA) and PsAID12 were best for those with higher disease activity. CONCLUSION: SRMs and MCII were relatively small in this real-world population, particularly among those with lower disease activity at baseline. BASDAI, cDAPSA, and PsAID12 had good sensitivity to change, but selection for use in trials should consider the baseline disease activity of patients to be enrolled.

Improvement of Functioning and Health With Ixekizumab in the Treatment of Active Nonradiographic Axial Spondyloarthritis in a 52-Week, Randomized, Controlled Trial.

OBJECTIVE: To evaluate the effect of ixekizumab on self-reported functioning and health in patients with active nonradiographic axial spondyloarthritis (SpA). METHODS: COAST-X was a randomized, controlled trial conducted in patients with nonradiographic axial SpA over 52 weeks. Participants were randomized at a ratio of 1:1:1 to receive 80 mg of ixekizumab subcutaneously every 4 weeks or 2 weeks or placebo for 52 weeks. Self-reported functioning and health end points included the Medical Outcomes Study Short Form 36 (SF-36) health survey, Assessment of Spondyloarthritis International Society (ASAS) health index, and European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) health-utility descriptive system. RESULTS: Compared to placebo, ixekizumab treatment resulted in improvement of SF-36 physical component summary scores from baseline, with a score of 4.7 improving to 8.9 with ixekizumab therapy every 4 weeks (P < 0.05) and a score of 9.3 with ixekizumab therapy every 2 weeks (P < 0.01); the greatest improvements were observed in the domains of physical functioning, role-physical, and bodily pain at weeks 16 and 52. A higher proportion of patients receiving ixekizumab therapy every 2 weeks reported ≥3 improvements based on the ASAS health index from baseline to weeks 16 and 52 (P < 0.05). Significantly more patients receiving ixekizumab every 4 weeks reported improvements in "good health status" on the ASAS health index (ASAS score of ≤5) at weeks 16 and 52 (P < 0.05). Patients receiving ixekizumab reported improvements on the EQ-5D-5L compared to those who received placebo at week 16 (0.11 versus 0.17 for patients receiving treatment every 4 weeks and 0.19 for patients receiving treatment every 2 weeks; P < 0.05), which remained consistent at week 52. There were no clinical meaningful differences in responses based on the ixekizumab dosing regimen for patients who received ixekizumab therapy every 2 weeks or every 4 weeks. CONCLUSION: In patients with nonradiographic axial SpA, therapy with ixekizumab was superior to placebo in the improvement of self-reported functioning and health at weeks 16 and 52.

The American College of Rheumatology Fibromyalgia Criteria Are Useful in the Evaluation of Fibromyalgia Symptoms in Patients With Ankylosing Spondylitis: A Cross-Sectional Study.

BACKGROUND: Fibromyalgia (FM) is common among patients with ankylosing spondylitis (AS), and its coexistence is believed to interfere with the measurement of patient-reported outcomes of disease activity and function in AS because of overlapping symptoms between the 2 diseases. This can confound clinical assessment and treatment decisions. AIMS: The aim of this study was to assess the relationship between the Fibromyalgia Symptom Scale (FSS) and its components, the Widespread Pain Index (WPI), and System Severity Scale with measures of disease activity, function, and patient-reported outcomes in AS. METHODS: We recruited 63 AS patients (aged ≥18 years) meeting the modified New York criteria, and Bath Ankylosing Spondylitis Disease Activity Index, Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein, Routine Assessment of Patient Index Data 3, and Bath Ankylosing Spondylitis Functional Index questionnaires were administered to them. The presence of FM was determined using validated 2010 American College of Rheumatology diagnostic criteria for FM. RESULTS: Twenty-eight of 63 patients (44.4%) with AS and FM had higher disease activity and greater impairment of functional ability compared with AS patients without FM. Using multiple linear regression estimates, there was no significant relationship of FSS scores with Bath Ankylosing Spondylitis Disease Activity Index (p = 0.36), Routine Assessment of Patient Index Data 3 (p = 0.50), Ankylosing Spondylitis Disease Activity Score-C-Reactive Protein (p = 0.24), Bath Ankylosing Spondylitis Functional Index (p = 0.42) scores, or erythrocyte sedimentation rate (p = 0.82) and C-reactive protein (p = 0.75). CONCLUSIONS: Despite a high prevalence of FM in our patients with the diagnosis of AS, there was no relationship between FSS and measures of disease activity or function in AS, suggesting that FSS and its components could be a useful tool to assess FM in AS patients. Also, FM impairs functional ability in patients with AS.

Recognizing Axial Spondyloarthritis: A Guide for Primary Care.

Axial spondyloarthritis (axSpA) is an important cause of chronic low back pain and affects approximately 1% of the US population. The back pain associated with axSpA has a characteristic pattern referred to as inflammatory back pain (IBP). Features of IBP include insidious onset before age 45 years, association with morning stiffness, improvement with exercise but not rest, alternating buttock pain, and good response to treatment with nonsteroidal anti-inflammatory drugs. In patients with IBP, it is essential to look for other features associated with spondyloarthritis (SpA), such as enthesitis, dactylitis, peripheral arthritis, extra-articular manifestations (eg, psoriasis, uveitis, or inflammatory bowel disease), human leukocyte antigen B27 positivity, and a family history of SpA. Axial SpA is underrecognized, and a delay of several years between symptom onset and diagnosis is common. However, with new and effective therapies available for the treatment of active axSpA, early recognition and diagnosis are of critical importance. For this narrative review, we conducted a literature search of English-language articles using PubMed. Individual searches were performed to identify potential articles of interest related to axSpA (search terms: ["axSpA" OR "axial SpA" OR "axial spondyloarthritis" OR "ankylosing spondylitis"]) in combination with terms related to IBP ("inflammatory back pain" OR "IBP" OR "chronic back pain" OR "CBP" OR "lower back pain" OR "LBP"), diagnosis (["diagn∗" OR "classification"] AND ["criteria" OR "recommend∗" OR "guidelines"]), and referral ("refer∗"). No date range was formally selected, as we were interested in providing an overview of the evolution of these concepts in clinical practice. We supplemented the review with insights based on our clinical expertise. Patients with chronic back pain should be screened for IBP and other SpA features; suspicion for axSpA should trigger referral to a rheumatologist for further evaluation.

Glucocorticoid-induced osteoporosis: Insights for the clinician.

Glucocorticoids cause significant bone loss, predominantly affecting trabecular bone, with consequent fragility fractures. The risk of fractures is related to the dose and duration of glucocorticoid use, but an increased risk may be observed even at low doses and even in the first month of treatment. Steps to prevent or treat osteoporosis should be considered in all patients who take the equivalent of prednisone at a dose of 2.5 mg or more per day for 3 or more months.

Racial Differences in Clinical Features and Comorbidities in Ankylosing Spondylitis in the United States.

OBJECTIVE: To examine racial differences of clinical features, medication usage, and comorbidities of patients with ankylosing spondylitis (AS) in the United States. METHODS: In the Explorys database, 28,520 patients with AS were identified. Data were stratified by 2 rheumatology visits, race, sex, clinical characteristics, medication use, and comorbidities. Datasets were recorded as proportions, which were compared using chi-square test (p < 0.05). RESULTS: Of the 10,990 patients with AS, 8% were African Americans and had elevated erythrocyte sedimentation rate and C-reactive protein, and high frequency of anterior uveitis, hypertension, diabetes, depression, and heart disease. CONCLUSION: African Americans with AS in the United States have high disease activity and comorbidities compared to whites.

The Paradox of Bone Formation and Bone Loss in Ankylosing Spondylitis: Evolving New Concepts of Bone Formation and Future Trends in Management.

PURPOSE OF REVIEW: The purpose of the study is to briefly review the molecular mechanisms that leads to structural damage in ankylosing spondylitis (AS), defined as new bone formation resulting in complete or incomplete ankylosis of the spine, and the impact of treatment with biologics to retard this process. RECENT FINDINGS: The understanding of molecular mechanisms leading to new bone formation in AS has significantly improved but is still incomplete. Availability of biologics has greatly enhanced the treatment of patients with AS, but its impact on slowing the structural damage is still a matter of debate, although a few observational studies have shown that long term use of TNF-α blockers may slow radiographic progression. The availability of newer biologics targeting IL-17/1L23 has shown some promising results in slowing radiographic progression in AS. Although the availability of TNF-inhibitors has greatly enhanced the treatment options for patients with AS, their impact on slowing the structural damage is still not clearly established. However, preliminary results using newer biologics targeting IL-17/1L23 axis are more encouraging but longer follow-up is needed.

Utility of DXA scanning and risk factors for osteoporosis in ankylosing spondylitis-A prospective study.

BACKGROUND: Conventional DXA imaging of spine and hip to measure bone mineral density (BMD) has limitations in patients with ankylosing spondylitis (AS). We investigated the correlation of hip and spine BMD measurements in patients with AS to determine if hip DXA will prove clinically useful while avoiding the confounding effect of spinal disease. Also, we studied risk factors for osteoporosis (OP) and osteopenia in AS. METHODS: We randomly identified patients from our validated AS registry ≥18 years of age who met the Modified New York Classification criteria for AS. BMD was measured and interpreted using ISCD 2007 guidelines and diagnosis of OP was based on WHO criteria. ESR, CRP, urinary N-telopeptide, and 25-hydroxy vitamin D were also measured. Correlation between the BMD (total hip and/or femoral neck) and lumbar spine was calculated. Statistical comparisons between the 2 sites, lumbar spine (AP) and hip (total hip and or femoral neck) were made using Bowker's test for symmetry and kappa statistics. Chi-square and odds ratio using logistic regression were used to assess the association of the purported risk factors for OP in these patients. RESULTS: Frequency of OP among AS patients ≥50 years of age was 23%, and that of osteopenia was 41%. Among patients <50 years of age, the frequency of low bone mass for expected age (Z-score ≤-2.0) was 14.7%. There was moderate correlation (ρ = 0.59) and a fair agreement (κ = 0.26; 95% CI: 0.10-0.42) between the lowest T-values of hip and lumbar spine (AP view). OP was significantly associated with elevated CRP level [OR = 4.2 (95% CI: 1.13-15.9), p < 0.03] and African American race [OR = 7.2 (95% CI: 1.18-44.99), p < 0.03]. CONCLUSION: Our results demonstrated a moderate correlation and fair agreement between the T-scores of hip and the lumbar spine (AP view) in patients with AS, suggesting that DXA of the hip and the lumbar spine (AP view) may both be useful for OP and osteopenia screening in patients with AS without fused spines. We confirm the previous reports of an association of elevated CRP level with an increased risk of OP in patients with AS, but this is the first study to demonstrate that African American patients with AS may be at a higher risk of developing OP compared to Caucasians.

Clinical utility, safety, and efficacy of pregabalin in the treatment of fibromyalgia.

Fibromyalgia is a chronic debilitating medical syndrome with limited therapeutic options. Pregabalin, an anticonvulsant and α-2-Δ subunit receptor ligand, is one of the anchor drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. The drug has shown clinically meaningful benefits across multiple symptom domains of fibromyalgia. Efficacy of pregabalin in fibromyalgia pain has been evaluated in at least five high-quality randomized trials, two long-term extension studies, a meta-analysis, a Cochrane database systematic review, and several post hoc analyses. These studies also hint towards a meaningful benefit on sleep, functioning, quality of life, and work productivity. Side effects of pregabalin, although common, are mild to moderate in intensity. They are noted early during therapy, improve or disappear with dose reduction, and are not usually life- or organ threatening. In most patients, tolerance develops to the most common side effects, dizziness, and somnolence, with time. With close clinical monitoring at initiation or dose titration, pregabalin can be effectively used in primary care setting. Pregabalin is cost saving with long-term use and its cost-effectiveness profile is comparable, if not better, to that of other drugs used in fibromyalgia. In the present era of limited therapeutic options, pregabalin undoubtedly retains its role as one of cardinal drugs used in the treatment of fibromyalgia. This review intends to discuss the clinical utility of pregabalin in the management of fibromyalgia with a focus on efficacy, safety, and cost-effectiveness.

Identification of plasma microRNA expression profile in radiographic axial spondyloarthritis-a pilot study.

At present, there are no studies that have established a microRNA (miRNA)-based signature profile in patients with radiographic axial spondyloarthritis (rad-axial SpA), and we hypothesized that these patients may have aberrantly expressed circulating miRNAs reflective of underlying disease and inflammation. This study aims to determine the expression profile of miRNAs in plasma of patients with rad-axial SpA and compare it with healthy, age, and sex-matched controls. Fifteen subjects with rad-axial SpA based on ASAS classification criteria and 5 controls were recruited from our local SpA registry. Demographic data were collected and disease activity was measured using Bath Ankylosing Spondylitis Disease Activity Index (BASDI). Peripheral blood samples (5 ml) were obtained from eligible consenting patients and controls. RNA from the plasma was prepared using miRNeasy kit (Qiagen) by a modified protocol. Expression of 175 miRNAs was screened in the plasma of all 15 patients and 5 controls using serum/plasma miRNA PCR arrays (Exiqon Inc. Woburn, MA) essentially following the manufacturer's instructions. Real-time PCR was carried out on StepOne Plus (Applied Biosystems) and the data was extracted and analyzed using ExiGen Enterprise software (MultiD, Göteborg, Sweden). Potential miRNA targets were identified using bioinformatics. ESR and CRP levels were measured by standard laboratory methods. We identified 7 differentially expressed miRNAs (2 upregulated and 5 downregulated). miR-34a, which was overexpressed in patients with rad-axial SpA, was predicted to target BMP-3 mRNA by TargetscanS and PicTar miRNA target algorithms. miR-150 was downregulated in all of the samples analyzed by us using the TaqMan Gene Expression assay. The most repressed miRNA was miR-16 and is predicted to regulate the expression of activin A receptor (ACVR2B), a receptor for growth, and differentiation factor-5 (GDF-5). Our data indicates that (1) patients with axial SpA, as compared to controls, have dysregulated expression of selected miRNAs in the plasma; and (2) the differentially expressed miRNAs are predicted to target genes that play a role in bone morphogenesis, growth, and immune response.

High frequency of fibromyalgia in patients with psoriatic arthritis: a pilot study.

Background. Widespread pain from fibromyalgia syndrome (FMS) is observed in patients with psoriatic arthritis (PsA). We hypothesized that there is increased frequency of FMS in patients with PsA that contributes to fatigue and pain. Method. We prospectively enrolled patients with PsA based on the Classification criteria for Psoriatic Arthritis and healthy subjects were used as controls. The frequency of FMS was determined using London Fibromyalgia Epidemiologic Study Screening Questionnaire (LFESSQ) and Symptoms Intensity scale (SIs). Results. 34 PsA patients and 44 controls fulfilled the inclusion criteria. Median age of PsA patients was 52 years with 53.33% females. Median age of controls was 50.5 years with 59% females. FMS was present in 53.33% of PsA patients compared to 4.54% of the controls (P < 0.001), based on LFESSQ. 37.50% of PsA had FMS compared to 6.66% of controls (P < 0.001) based on SIs. There was a significant correlation between LFESSQ and SIs in the psoriatic group (P = 0.00243). 76.66% of PsA patients complained of fatigue compared to 40.90% of controls, but the mean fatigue score between the two groups was comparable (5.03 versus 5.18). Conclusion. FMS-associated pain and fatigue are significantly more frequent in patients with PsA compared to controls.

Persistent hematuria after induction of remission in Wegener granulomatosis: a therapeutic dilemma.

Wegener granulomatosis (WG) is a systemic disease that is often associated with an immune-mediated form of glomerulonephritis (GN). Renal disease most often manifests as microscopic hematuria with or without red blood cell or mixed cellular casts, proteinuria, and an elevated serum creatinine concentration.We conducted the current study to determine whether persistent hematuria, in the setting of apparent clinical remission, may reflect glomerular injury and not active renal disease. We performed a retrospective analysis of data from 82 patients with new-onset WG, of whom 25 had GN at presentation.Twenty of 25 patients with GN achieved sustained remissions (>6 consecutive months' duration). During initial periods of active disease the median peak serum creatinine was 1.9 mg/dL (range, 0.6-13.6 mg/dL). The median time to remission was 4 months (range, 2-13 mo). After effective therapy, median creatinine was 1.1 mg/dL (range, 0.4-1.8 mg/dL). Ten of 20 patients had prolonged hematuria over a period of >6 months. Within this subset, 5 subsequently normalized urine over a median period of 11 months and 5 did not achieve normal urine sediment over a median follow-up of 38 months. Thus, 10 of 25 patients with WG and GN had sustained hematuria in spite of apparent prolonged clinical remission.Patients with WG and GN may achieve enduring remissions that allow withdrawal of medications in spite of continued microscopic hematuria with or without red blood cell casts that may persist for months or even years. Continued use of aggressive immunosuppressive therapies in such patients would be ill-advised and could lead to irreversible and even life-threatening side effects from cyclophosphamide or high-dose corticosteroids.

Do acute-phase reactants predict response to glucocorticoid therapy in retroperitoneal fibrosis?

OBJECTIVE: To determine the value of the erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP) level at the time of diagnosis for predicting radiographic response to glucocorticoid therapy in patients with retroperitoneal fibrosis (RFP). METHODS: Data were collected retrospectively for 37 patients with an established diagnosis of RFP (the diagnosis was proven by biopsy in 31 patients), all of whom met the following inclusion criteria: 1) availability of a recorded baseline ESR and/or CRP level and results of computed tomography or magnetic resonance imaging, 2) availability of followup CRP level and/or ESR with radiographic imaging 12-24 weeks after initiation of therapy, and 3) treatment with prednisone monotherapy at a starting dosage of 40-60 mg daily. Patients were divided into 2 therapeutic response groups: group 1 showed radiographic regression, and group 2 showed no change or radiographic progression. Any progression or regression was determined by an estimated change of > or =25%. RESULTS: The median baseline CRP levels were 2.2 mg/dl (interquartile range [IQR] 1.4-8.0) in group 1 and 1.2 mg/dl (IQR 0.8-4.1) in group 2 (P = 0.35). The median baseline ESR in group 1 was 57.5 mm/hour (IQR 39.2-102.5), which was not statistically different from the median ESR in group 2 (58 mm/hour [IQR 33-66]). The mean CRP level and ESR tended to be higher in patients with radiographic regression, but these differences failed to reach statistical significance. Spearman's correlation coefficient revealed no correlation between the baseline CRP level (r = -0.11, P = 0.51) or ESR (r = -0.06, P = 0.71) and the radiographic response. CONCLUSION: The ESR and CRP level at baseline are poor predictors of a therapeutic response to glucocorticoid therapy in patients with RPF.