Efficacy of tofacitinib on enthesitis in patients with active psoriatic arthritis: analysis of pooled data from two phase 3 studies.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). This post hoc analysis assessed tofacitinib efficacy on enthesitis by baseline location and severity, and impact on disease activity and patient-reported outcomes (PROs), in patients with PsA. METHODS: Data were pooled from two phase 3 studies (NCT01877668/NCT01882439) in patients with PsA receiving tofacitinib 5 or 10 mg twice daily to month (M)6 or placebo to M3. Endpoints were: change from baseline in Leeds Enthesitis Index (LEI) or Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC); proportions of patients with enthesitis, relapsed enthesitis after resolution, de novo enthesitis, low disease activity (LDA) or remission (minimal disease activity/very low disease activity; Psoriatic Arthritis Disease Activity Score; Disease Activity Index for Psoriatic Arthritis, and Composite Psoriatic Disease Activity in Psoriatic Arthritis); and PROs (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] total and arthritis pain Visual Analog Scale scores). Descriptive statistics were generated by visit and treatment. Change from baseline in PROs was evaluated by multivariate linear regression. RESULTS: Seven hundred ten patients from two studies were included: 479 had LEI > 0; 545 had SPARCC > 0; and 136 had LEI = 0 and SPARCC = 0 at baseline. At baseline, among patients with LEI > 0 or SPARCC > 0, mean LEI and SPARCC across treatments and enthesitis locations/severities ranged from 1.0-4.4 and 1.3-9.4, respectively. Across several baseline enthesitis locations/severities, changes from baseline in LEI and SPARCC up to M3 were greater with tofacitinib (-2.0-0.4 and -3.5-0.2) vs placebo (-|0.9-|0.4 and -1.5-1.1). Enthesitis at M6 was more common in patients with greater baseline enthesitis severity. At M6, ≤ 40% of patients with baseline LEI > 0 or SPARCC > 0 whose enthesitis had resolved by M1/M3 experienced a relapse, and < 14% of patients with baseline LEI = 0 and SPARCC = 0 had de novo enthesitis. LDA/remission rates generally increased with tofacitinib over time. Baseline LEI location was significantly associated with change from baseline in arthritis pain score, while baseline SPARCC severity was significantly associated with change from baseline in FACIT-F total and arthritis pain scores. CONCLUSION: Tofacitinib treatment resulted in improvements in enthesitis in patients with PsA, regardless of baseline location or severity. TRIAL REGISTRATION: NCT01877668;NCT01882439.

The Psoriatic Arthritis Experience in Saudi Arabia from the Rheumatologist and Patient Perspectives.

BACKGROUND: Psoriatic arthritis (PsA) is a musculoskeletal disease that adversely affects physical mobility and quality of life. It is challenging to manage because of the heterogeneous nature of the symptoms and the current treatment options. PURPOSE: To explore the patient and rheumatologist perspectives of PsA to help improve understanding of the disease experience and improve disease management. METHODS: A descriptive, observational cross-sectional study of Saudi Arabian dermatologists and rheumatologists and patients with psoriasis or PsA was conducted. Questionnaire data were collected from 31 dermatologists, 34 rheumatologists, 90 patients with psoriasis, and 98 patients with PsA and analysed using descriptive statistics. Here, data from rheumatologists and patients with PsA are presented. RESULTS: The results revealed similarities and differences in the rheumatologist and patient perspectives of PsA. Rheumatologists and patients agreed on the impact that PsA had on patients' quality of life and that more education was needed. However, they differed on several aspects of disease management. Rheumatologists estimated the time to diagnosis as four times shorter than what patients experienced. Patients accepted their diagnosis more than rheumatologists perceived them to; rheumatologists perceived patients to be worried or fearful. Patients perceived joint pain as their most severe symptom, in contrast to rheumatologists, who presumed skin appearance was the most severe symptom. Reported input into PsA treatment goals differed significantly. More than half of the rheumatologists reported equal patient-physician input into goal development as opposed to <10% of patients reporting the same. Almost half of patients reported no input into the development of their treatment goals. CONCLUSION: The management of PsA could benefit from enhanced screening and re-evaluation of what PsA outcomes have the most value to patients and rheumatologists. A multidisciplinary approach is recommended with increased patient involvement in disease management and individualized treatment options.

Consensus-based recommendations on the diagnosis, referral and clinical management of patients with psoriatic arthritis.

Psoriatic arthritis (PsA) is a highly heterogeneous disease with complex manifestations. Limited understanding of the disease and non-availability of local guidelines pose challenges in the management of PsA in Saudi Arabia. Therefore, this expert consensus is aimed to provide recommendations on the management of patients with PsA, including referral pathway, definition of remission and treat-to-target (T2T) approach. A Delphi technique of consensus development was used involving an expert panel comprised of 10 rheumatologists, one dermatologist and one family physician. Based on the review of available published evidence and the opinions of clinical experts, key recommendations were developed. A consensus was achieved in defining the following: management guideline adaptable for Saudi Arabia, most useful screening tool, laboratory investigations, imaging tests and criteria for referring suspected PsA patients to a rheumatologist. In addition, an agreement was achieved in defining the T2T strategy and remission for the clinical management of PsA. Overall, these recommendations provide an evidence-based framework for the management of PsA patients in Saudi Arabia.

The Delay of Diagnosis in Spondyloarthropathy Patients in a Tertiary Hospital in Saudi Arabia.

Objective Seronegative spondyloarthropathies (SpA) are a group of rheumatological disorders that share the common feature of being rheumatoid factor negative. Inflammation of the sacroiliac joint is considered the hallmark of ankylosing spondylitis (AS). On the other hand, psoriatic arthritis (PsA) affects patients with psoriasis. It is characterized by asymmetrical oligoarticular arthritis. Involvement of the distal interphalangeal joint is a unique feature of PsA. Enteropathic arthritis (EnA) involves the presence of inflammatory arthropathy in patients with inflammatory bowel disease (IBD). These diseases are strongly associated with the HLA-B27 gene. Although they are significantly disabling, their diagnosis has been frequently delayed. Early diagnosis is associated with early treatment, and thus better disease outcomes. The aim of this study was to evaluate the diagnostic delay (DD), that is, the duration between onset of symptoms and diagnosis, of SpA patients and its relation to the demographic characteristics, disease activity, measured by ankylosing spondylitis disease activity score (ASDAS) and bath ankylosing spondylitis disease activity index (BASDAI) scores, and the HLA-B27 status of Saudi SpA patients. Methods The data of 94 patients who were diagnosed with SpA were collected from medical records and from them personally. The data included patient demographics, age at diagnosis, delay of diagnosis, in years, disease activity (BASDAI and ASDAS scores), HLA-B27 status and C-reactive protein levels (CRP). The data were analyzed using Statistical Package for the Social Sciences for Windows version 21.0 (SPSS Inc., Chicago, IL, USA). Results 50% of patients were females. The mean DD was (mean ± SD) 4.98 ± 6.00 (range: 0-35). The average age of symptoms onset was 30.70 ± 11.30 (range: 8-59) and the average age at diagnosis was 35.65 ± 10.80 (range: 16-60). The mean BASDAI and ASDAS scores were 3.05 ± 2.21 and 2.29 ± 1.01, respectively. The majority of the patients had high disease activity (35.1 %). 25.0% were HLA-B27 positive. 83.7 % had normal CRP. There was no statistically significant difference between DD and gender, HLA-B27 status, ASDAS and BASDAI scores, and CRP. The DD was significantly higher in AS patients when compared to PsA (p-value= 0.048) and EnA patients (p-value < 0.0001). There was a statistically significant weak anticorrelation between DD and the age at symptoms onset in PsA patients (r-value= -0.39, p-value= 0.003). Age at diagnosis was statistically significantly higher in patients with PsA when compared to EnA. There was no correlation between DD and the disease activity in SpA patients. Conclusion The means of DD in AS, PsA, and EnA patients were 6.69 ± 5.83, 3.67 ± 6.42 and 2.00 ± 1.60, respectively. DD was greater in AS patients when compared to PsA and EnA patients. Early detection and referral to rheumatologists should be addressed, as early intervention is associated with favorable disease outcomes.

Risk Factors Associated with Methotrexate Intolerance in Rheumatoid Arthritis Patients.

BACKGROUND: Methotrexate (MTX) Intolerance Severity Score (MISS) has been previously validated in the Arabic language and has helped to detect high levels of intolerance in rheumatoid arthritis (RA) patients. The aim of the current study was to evaluate patient and disease characteristics associated with a high risk of MTX intolerance. MATERIALS AND METHODS: A cross-sectional interview-based survey was conducted using adult RA patients as a study group, who were visiting a specialized rheumatology clinic at King Saud University Medical City. The Arabic MISS was used in this survey. Statistical analyses were performed to understand associations between MTX-intolerant and MTX-tolerant patients. RESULTS: A total of 117 patients were involved in this study. Of those, 101 (86.3%) were females with a mean (SD) disease duration of 6.6 (5.7) years. The median (interquartile range (IQR)) Disease Activity Score-28 (DAS28) was 3.6 (3.6-4.1). MTX intolerance was observed in 55 (47%) patients. The most predominant component in patients with a positive test was the behavioral component. Intolerant patients had a higher median of pain (47.3 vs. 50.0; P = 0.010) and patient global assessment (50.0 vs. 60.0; P = 0.004) scales compared to those in tolerant patients. Additionally, MTX intolerance was associated with the female gender (adjusted odds ratio (AOR) 6.724; 95% CI 1.420, 31.843, P = 0.016), marital status (AOR 2.549; 95% CI 1.037, 6.270, P = 0.042) and DAS28 (AOR 1.612; 95% CI 1.032, 2.517, P = 0.036). There was no significant difference between the two groups in the remaining disease activity parameters, background therapies, seropositivity, and smoking status (P > 0.05). CONCLUSION: Patient characteristics, rather than disease activity, significantly impact MTX intolerance. Behavioral component is the main driver of intolerance. Intolerant patients have higher patient-reported outcomes. Qualitative studies are needed to explore causes and potential solutions to MTX intolerance.

Disease burden and treatment challenges of psoriatic arthritis in Africa and the Middle East.

Psoriatic arthritis (PsA) is a chronic, inflammatory arthropathy occurring in up to 30% of patients with psoriasis, and is characterized by multiple manifestations including peripheral arthritis, enthesitis, dactylitis, spondylitis, and psoriatic skin and nail disease. This complex and heterogeneous disease is poorly understood and its diagnosis and treatment are suboptimal, particularly in Africa and the Middle East, where very few studies into the impact of PsA have been carried out. This article aims to highlight the disease burden of PsA in the region as well as to identify unmet clinical needs. A non-systematic review was carried out in the PubMed database and the most relevant publications were selected. Expert rheumatologists practicing in Africa and the Middle East provide an insight into the challenges of treating PsA in daily practice, along with recommendations for improvements.

Fatigue in Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis: Analysis from a Longitudinal Observation Cohort.

OBJECTIVE: In this study, we aimed to address the prevalence of fatigue, its associated factors, and the effect of tumor necrosis factor inhibitors (TNFi) on this subgroup of patients in a large axial spondyloarthritis (axSpA) cohort. METHODS: The study included 681 patients [ankylosing spondylitis (AS) and nonradiographic axSpA (nr-axSpA)]. The Fatigue Severity Scale (FSS) and the Bath AS Disease Activity Index question 1 (BASDAI Q1) indices were used for fatigue assessment. Severe fatigue was defined as an FSS ≥ 4 or a BASDAI Q1 ≥ 5. Disease activity, function, and quality of life (QoL) measures were recorded. Patients who had been treated with TNFi were identified, and baseline and followup data were analyzed. RESULTS: Of the cohort, 67.3% had severe fatigue, and the prevalence was similar between AS (67.2%) and nr-axSpA (68.2%). Severely fatigued patients tended to have higher disease activity scores, increased acute-phase proteins, and decreased QoL measures. TNFi therapy was associated with improvement in disease activity, and although this treatment led to significantly decreased fatigue scores, this reduction was not optimal in the majority of patients with 80% continuing to have severe fatigue according to their posttreatment scores. Health Assessment Questionnaire, mean scores of BASDAI Q5 and Q6, and BASDAI enthesitis were independent predictors of fatigue severity. CONCLUSION: Fatigue is a common symptom in axSpA, and the burden of fatigue among patients with nr-axSpA is similar to that seen in AS. While biologics are effective in improving disease activity, their effect on fatigue is more limited. In axSpA, fatigue remains unresponsive to TNFi in nearly 80% of patients.