Minimal and Low Disease Activity Among Psoriatic Arthritis Patients in the UAE: a Multi-Center Cross Sectional Study

Tala El Tal¹, Bhavna Khan², Richard Kirubakaran³, Ghita Harifi⁴ and Humeira Badsha^4*

¹Department of Rheumatology, the Hospital for Sick Children, Toronto, Canada

²Department of Rheumatology, King’s College Hospital, Dubai, UAE

³South Asian Cochrane Network, Vellore, India

⁴Department of Rheumatology, Dr. Humeira Badsha Medical Center, Dubai, UAE

*Corresponding Author:

Humeira Badsha
Department of Rheumatology, Dr. Humeira Badsha Medical Center, Dubai, UAE
E-mail: doctorbadsha@gmail.com

Received: 06-Aug-2024, Manuscript No. fmijcr-24-144646; Editor assigned: 08- Aug-2024, Pre-QC No. fmijcr-24-144646 (PQ); Reviewed: 22-Aug-2024, QC No. fmijcr-24-144646; Revised: 27- Aug- 2024, Manuscript No. fmijcr-24-144646 (R); Published: 31-Aug-2024, DOI: 10.37532/1758-4272.2024.19(8).188-193

Abstract

Aim: This study aims to (1) Describe a multi-ethnic cohort of PsA patients seen in rheumatology centers in UAE, in terms of socio-demographic features, clinical and disease characteristics, and treatment trends (2) Explore relationship between active combination (biologics and methotrexate (MTX)) or MTX users and achieving minimal disease activity (MDA).

Methods: Patients ≥ 18 years with PsA from a database of two rheumatology centers in the UAE were included. Continuous data were presented as mean and standard deviation (SD); dichotomous data were presented as percentages. To estimate the treatment effect on MDA the odds ratio and 95% confidence interval (CI) were calculated.

Results: 143 patients were included (mean age 43.5 (SD: 10.2), 60% male; ethnicity: South Asian (45%), Arab (16%) and Caucasian (33%)). Using Disease Activity in Psoriatic Arthritis (DAPSA) scores, 29 (18%) were in remission, 65 (45%) in low disease activity (LDA), 32 (22%) moderate disease activity and 17 (11%) in high disease activity (HDA). Using the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) scores, MDA was achieved in 88/143 (62%). Active users of combination therapy (OR 4.8, 95% CI [1.29, 17.8]; p = 0.02) or biologics alone (OR 5.36, 95% CI [2.10, 13.70]; p=0.0004) were at increased odds of achieving MDA.

Conclusion: this study provides insight on the epidemiology, disease and treatment trends in PsA in UAE where by majority of our PsA patients that were largely on biologics or combination therapy, had well controlled disease. This supports the early use of biologics in treatment of PsA.

Keywords

Psoriatic arthritis● Epidemiology● Minimal disease activity● Biologics● Methotrexate

Introduction

Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease made up of a plethora of clinically diverse and heterogeneous phenotypes including peripheral arthritis, dactylitis, enthesitis, skin psoriasis and nail disease or predominantly axial disease [1]. It exists in 30% of patients with established skin psoriasis [2]. PsA is often aggravated by its known associations with multiple comorbidities including metabolic syndrome, obesity, cardiovascular disease, and depression [3]. More than half of patients with PsA develop progressive, erosive arthritis, often associated with functional impairment and reduced quality of life [4,5]. As such, early diagnosis and timely intervention are crucial for optimal patient care. It is well recognized that there is considerable variation in the reported prevalence across geographic regions ranging from 0.25% in the United States to 0.19% in Europe [6,7]. This is partly explained by the variable expression of HLA-B27, different demographics and methodologic characteristics. As for the prevalence and incidence of PsA in the Middle East and North Africa (MENA) region, the reporting is sporadic and inconsistent with very few published studies available. This particular issue was recently highlighted in a non-systematic review by Bedaiwi et al calling for more epidemiological studies of PsA in the region [8]. Moreover, the heterogeneity of PsA also presents a considerable challenge in treatment as one drug does not fit all phenotypes. For some time, methotrexate (MTX), a conventional disease-modifying anti-rheumatic drug (DMARD), remains one of the most widely used medications in the treatment of PsA [9]. In the last decade, the treatment of PsA has transformed by the introduction and use of biological DMARDs (bDMARDs) and synthetic DMARDs (tsDMARDs), targeting proinflammatory cytokines, such as a tumor necrosis factor (TNF), interleukin IL-12/Il-23 and IL-17, and inhibiting phosphodiesterase-4 (PDE4) or Janus kinases (JAKs) respectively [10]. While the efficacy of MTX is known in Rheumatoid Arthritis (RA), firm evidence from a placebo-controlled trial to support its use in PsA is scant [11]. Published in 2012, the Methotrexate in Psoriatic Arthritis (MIPA) study, the largest randomized placebo-controlled trial of MTX in PsA, found no significant effect of MTX compared with placebo on American College of Rheumatology 20% improvement criteria (ACR20) although it improved skin disease [12]. On the other hand, the Tight Control in PsA (TICOPA) study, an open-label multicenter randomized controlled trial of 206 DMARD naïve patients with early PsA, found some benefit of MTX at higher doses whereby almost 40% of patients in the tight control (treat-to-target arm) were in minimal disease activity (MDA) at 48 weeks, compared with 25% in the standard care arm [13]. Similarly, the open label Remicade Study in Psoriatic Arthritis Patients Of Methotrexate-Naive Disease (RESPOND) trial which compared MTX monotherapy with MTX plus infliximab combination therapy, found that ACR20 response was achieved in 66.7% of patients in the MTX monotherapy arm although the combination arm was still superior [14]. Despite these observed clinical benefits in PsA, both studies lacked a placebo comparator due to the open label nature [15]. In addition, evidence from RCTs and observational studies suggest that MTX has limited disease-modifying effect in PsA [16,17]. For instance, the Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis (SEAM-PsA) study showed that 10.6% of patients treated with MTX monotherapy still had radiographic progression from baseline at 48 weeks [18]. Remission (REM) and low disease activity (LDA) is a difficult target for the majority of patients with PsA [19]. In spite of the lack of evidence from high-quality RCTs, MTX remains recommended as first line choice treatment in the latest European League Against Rheumatism (EULAR) recommendations in PsA [20]. In contrast, the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) considers other conventional DMARDs including MTX without a definite preference [21,22]. In response to the low-quality available evidence of MTX in PsA, the ACR/National Psoriasis Foundation (NPF) PsA Treatment Guidelines conditionally recommend the use of an anti-TNF biologic over MTX or other oral small molecules in treatment-naïve patients with active PsA [23]. To date, there is very little data about the epidemiology, the disease burden and treatment trends of PsA in the Middle East [8,24,25]. In response, the objective of this multi-center cross-sectional study is to (1) Describe the socio-demographics, clinical, disease, and treatment trends of our PsA cohort seen in rheumatology clinics in the United Arab Emirates (UAE). For disease trends, we will establish the percentage of our patients achieving LDA by DAPSA score or target of MDA as defined by the GRAPPA group. In addition, we also aim to (2) explore the relation of active treatment use and achieving MDA. Ultimately, this could potentially contribute to the understanding of PsA in the region particularly when there is no national registry. Additionally, this sheds light on the role of conventional and bDMARDs in treating PsA in the Middle East.

Methods

Subjects and study variables

We conducted a multi-center cross-sectional study at two Rheumatology Centers over a 3-year period from July 2018 – March 2020 at a specialized arthritis center and a rheumatology clinic in Dubai, UAE. We recruited consecutive patients over the age of 18 who fulfilled at their first visit to our clinic the ACR classification criteria for PsA (CASPAR). They had to have at least one follow up ≥ 6 months following initial treatment. Exclusion criteria included patients less than 18 years of age, patients with missing follow-up visits or multiple data entries, and patients having other types of inflammatory arthritis including rheumatoid arthritis, spondyloarthropathies, and inflammatory bowel disease-related arthritis. The study was approved by an internal ethics committee at the specialized arthritis center and was conducted in accordance with the recommendations of the Declaration of Helsinki. Informed consent was obtained. Demographics features such as age, height, weight, sex, ethnicity, insurance, employment status, marital status, education, body mass index (BMI), smoking status, family history of PsA and other autoimmune diseases, as well as comorbidities including obesity, dyslipidemia, hypertension, diabetes mellitus (DM), renal and liver disease, osteoarthritis, osteoporosis, stroke, myocardial infarction, thrombosis, pulmonary hypertension, gastritis, and joint replacement were obtained. Clinical data including delay to diagnosis in years, previous and current use of DMARDs specifically MTX monotherapy vs. combination therapy with bDMARDs, reasons for discontinuation of MTX as well as use of alternative therapies (acupuncture, ayurveda, traditional Chinese, herbal unani, homeopathy, and diet therapies) were recorded for all patients. All patients had a health assessment questionnaire disability index (HAQ-DI), disease activity in psoriatic arthritis score (DAPSA score), MDA, erythrocyte sedimentation rate (ESR), and C - reactive protein (CRP). HLA-B27 was collected for some patients at their first visit.

Statistical analysis

Continuous data are presented as mean ± standard deviation (SD). Dichotomous data were presented as percentages with/without absolute count. For normally distributed data, the difference in two groups’ means was analyzed using an independent t-test; binary data was analyzed using a χ² test (α = 0.05). A p-value of <0.05 was considered to be statistically significant. To estimate the treatment effect on MDA, the odds ratio and 95% Confidence interval were calculated and presented in a forest plot using RevMan 5.4 [26]. All statistical analyses were performed using the statistical package SPSS.

Results

Socio-Demographic features and comorbidities

A total of 143 consecutive PsA patients were included from July 2018 – March 2020, at a specialized arthritis center and rheumatology department of a multi-specialty medical center in Dubai, UAE. Table 1 summarizes the socio-demographic characteristics of this patient population. The mean age of the patients in years was 43.5 ±10.2 and were mainly male (60%) vs. female (40%). The patients were predominantly South Asian (n=64, 45%), while others included Caucasian (n=47, 33%), Arab (n=23, 16%), Far East (n=4, 3%) and Hispanic (n=2, 1%). Majority of the patients had a certain degree of education, and worked full time jobs (n=101, 70%). About 32% (n=46) patients smoked with a body mass index (BMI) of 27.8 ± 4.2. Comorbidities included dyslipidemia (n= 33, 23%), hypertension (n=34, 24%), and diabetes mellitus (n=19, 13%).

Clinical and disease characteristics

Using GRAPPA scores, of the 143 PsA patients, MDA was achieved in 62% (n=88) while 38% did not (n =55) (Table 2). Interestingly, there was a longer delay to diagnosis in those that did not achieve MDA, approximately 2.8 years ± 3.7 vs. 1.5 years ± 3 in those who achieved MDA. In addition, based on the HAQ-DI, most of our patients (n=139, 97.2%) had mild difficulties to moderate disability and none with very severe disability. Using the DAPSA scores, of the 143 PsA patients, almost half of the patients (n=65, 45%) achieved LDA and 29 (20%) achieved REM. However, 32 (22%) and 17 (11%) continued to have moderate and HDA respectively.

*HAQ-DI: Health Assessment Questionnaire-Disability Index; DAPSA: Disease Activity in Psoriatic Arthritis; MDA: Minimal Disease Activity using GRAPPA scores; DVT:  Deep Vein Thrombosis

Treatment

Table 3 summarizes the list of past or current treatments PsA patients received. About three quarters of patients received MTX (n=108, 76%), of which 27 (19%) used MTX alone, and 81 (57%) used it in combination with biologics. A small proportion of patients were on other disease-modifying anti-rheumatic drugs (DMARDs) including leflunomide (n=18, 13%) and sulfasalazine (n=15, 10%). In terms of biologics, most patients (n=98, 69%) received biologics at one point in time, mainly anti-TNF agents – adalimumab (n=47, 48%), etanercept (n=31, 32%), and infliximab (n=20, 20%). Interestingly, most of our patients (n=55, 38%) were on MTX monotherapy alone.

Factors related to minimal disease activity (MDA)

Table 4 presents the variables associated with MDA. The majority of our patients achieved MDA with age < 40 years, a shorter duration of PsA, and being on combination therapy with biologics. Patients receiving methotrexate monotherapy had lower chances of achieving MDA compared to those receiving a combination of methotrexate and biologics. Interestingly, we also found that obesity and smoking were not significantly associated with MDA achievement.

Some patients attempted multiple categories of biologics
*DMARD: Disease Modifying Anti-rheumatic Drug, MTX: Methotrexate

Discussion

Our findings show that our cohort of PsA patients in the UAE has a substantial disease burden, with only 62% achieving MDA. Early diagnosis and intervention remain key in reducing long-term morbidity and enhancing the chance of achieving MDA. Interestingly, our findings also show that biologic therapy in combination with MTX yields the best outcomes. This supports the current treatment paradigm as per GRAPPA and the ACR/NFP guidelines for PsA treatment, which recommend the use of biologic therapy for patients with high disease activity, especially when conventional therapies like methotrexate fail to achieve disease control [27, 28].

Conclusion

This study provides valuable insights into the clinical characteristics, treatment patterns, and disease activity levels of PsA patients in the UAE. The results indicate that while a significant portion of patients achieved minimal disease activity (MDA), a substantial number still experienced ongoing disease activity despite treatment. Moreover, combination therapy using biologics along with MTX showed better outcomes compared to MTX monotherapy. These findings emphasize the need for more aggressive and personalized treatment approaches to optimize outcomes for PsA patients. The study also highlights the importance of early intervention and the potential benefits of biologic therapies, in line with the latest treatment guidelines. Further research and longitudinal studies are necessary to validate these findings and enhance our understanding of PsA in the Middle East region.

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