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| ORIGINAL ARTICLE |
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| Year : 2022 | Volume
: 2
| Issue : 2 | Page : 53-57 |
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Psoriatic arthritis: Saudi retrospective observational study of manifestations and treatments
Seham R Alunizi1, AlRabbab AlShanqeeti1, Khalidah A Alenzi2, Ibrahim Abdulrazag Al-Homood1
1 Medical Specialties Department, Rheumatology Section, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia
2 Regional Drug Information and Pharmacovigilance Center, Tabuk Health Affairs, Ministry of Health, Tabuk, Kingdom of Saudi Arabia
| Date of Submission | 09-Sep-2022 |
| Date of Decision | 10-Oct-2022 |
| Date of Acceptance | 13-Oct-2022 |
| Date of Web Publication | 25-Jan-2023 |
Correspondence Address:
Dr. Ibrahim Abdulrazag Al-Homood
Medical Specialties Department, Rheumatology Section, King Fahad Medical City, P.O. Box 59046, Riyadh 11525
Kingdom of Saudi Arabia
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/ara.ara_14_22
Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory musculoskeletal disease associated with psoriasis. In this study, we aimed to assess clinical features and the response rates to various biological agents among patients with PsA in the Kingdom of Saudi Arabia. Materials and Methods: A retrospective study where 39 patients diagnosed with PsA based on ClASsification criteria for PsA criteria for the period 2015–2019, were recruited from rheumatology outpatient clinics at KFMC, Riyadh, Saudi Arabia. Results: Thirty-nine PsA patients (31 females [79.5%] and eight males [20.5%]) were reviewed. The median age at disease onset was 36 years (ranging from 20 to 61 years). The median disease duration was 3 years. Peripheral arthritis reported in 92% and axial involvement in 28.2% of our patients. Fifteen percent of our patients developed enthesitis, whereas 12.5% had dactylitis. The mean duration for adalimumab (ADA) as a first-line treatment was 104 weeks, whereas etanercept (ETA) was 120 weeks. However, ADA had the longest duration in the second-line therapy (177 weeks), and secukinumab (SEC) had the longest duration (209 weeks) in the third-line therapy. ADA was discontinued in 76.9% of our patients due to inefficacy, whereas the most adverse events were reported with SEC and ETA (7.1%). Conclusion: Our study provided insights on the demographics, characteristics, and responses to various biological treatments of PsA patients in Saudi Arabia.
Keywords: Characteristic, psoriatic arthritis, response, Saudi, spondyloarthritis
How to cite this article:
Alunizi SR, AlShanqeeti A, Alenzi KA, Al-Homood IA. Psoriatic arthritis: Saudi retrospective observational study of manifestations and treatments. Ann Rheumatol Autoimmun 2022;2:53-7 |
How to cite this URL:
Alunizi SR, AlShanqeeti A, Alenzi KA, Al-Homood IA. Psoriatic arthritis: Saudi retrospective observational study of manifestations and treatments. Ann Rheumatol Autoimmun [serial online] 2022 [cited 2023 Feb 4];2:53-7. Available from: http://www.ara.ssr.com/text.asp?2022/2/2/53/367436 |
| Introduction | |  |
Psoriatic arthritis (PsA) is an inflammatory musculoskeletal disease that might be associated with the presence of extra-articular manifestations (EAMs), such as psoriasis, uveitis, and inflammatory bowel disease.[1] It is characterized by high heterogeneity and complexity and affects multiple organ systems, including peripheral and axial joints, enthesitis, dactylitis, skin, and nails. However, clinical features could help to identify patients at risk of developing arthritis, and approximately one-third of patients with psoriasis will eventually develop PsA.[2],[3]
PsA's prevalence is approximately 133 per 100,000 people, and its incidence is approximately 83 per 100,000.[4] PsA's prevalence was reported equally among men and women; however, a consistent geographic variability in incidence was reported,[5] and the mean age at diagnosis was between 40 and 52 years.[6]
PsA-treatment goals are to achieve remission or minimize disease activity, including arthritis, spondylitis, enthesitis, dactylitis, and psoriasis, slow or prevent radiological progression, reduce the risk of comorbidities, and increase patient's life expectancy and quality.[7]
The management of PsA depends on understanding the pathogenesis as part of a multidisciplinary approach and the disease's severity. Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), for example, sulfasalazine, cyclosporine, and leflunomide could relieve the symptoms but without slowing radiographic progression, resolve axial symptoms, or relieve uveitis, enthesis, and dactylitis.[3]
On the other hand, tumor necrosis factor (TNF) inhibitors, interleukin-17 inhibitors (IL-17), IL-23 inhibitors, IL-12/-23 inhibitors, apremilast, abatacept, and Janus kinase inhibitors could treat multiple domains of the disease, including peripheral and axial arthritis, enthesitis, dactylitis, psoriasis, and nail disease, and reduce its radiographic progression.[3]
The selection of biologic agents depends on characteristics such as rapidity of onset, long-term efficacy, safety profile, and effects on comorbidities, which will result in higher persistence, more prolonged drug survival, higher patient satisfaction, and minimization of the disease's activity.[8]
TNF-α inhibitor (TNFi) agents, including etanercept (ETA), adalimumab (ADA), infliximab (INF), certolizumab pegol (CET), and golimumab, are the most often prescribed to treat patients with PsA.[9]
For patients who do not respond adequately to various TNF-α inhibitors, other biologics often prescribed, such as IL-17 inhibitor (i.e., secukinumab [SEC] or ixekizumab), IL-23 (i.e., guselkumab or risankizumab), or the IL-12/23 inhibitor (i.e., ustekinumab [UST]).
In observational studies, drug retention is considered a reliable indicator of overall treatment effectiveness. However, it is determined chiefly by drug efficacy and safety profile.
The EuroSpA research collaboration network investigated TNFi-naïve PsA patients initiating TNFi treatment retention and response rates. The retention rates at 12 months ranged from 68% to 90%, and at 24 months were 59%–89%. Moreover, The European registries showed that of TNFi withdrawals for all patients during the 24-month follow-up period, 63% occurred due to lack of efficacy, and 37% due to adverse events.[10]
Gubar et al. found retention rates of biologic therapies were worse among PsA patients with axial involvement and that IL inhibitors are preferable because the treatment retention rate does not depend on axial involvement.[11]
In a recent study, Klavdianou et al. included 75 patients treated with SEC. They found a survival rate of 64%, with a median retention rate of 26.8 months.[12] While Glintborg's study has shown that the mean anti-TNF drug survival rate is reduced significantly after shifting to a first anti-TNF agent by 2.2 years and 1.3 years with a second anti-TNF.[13]
Studies on PsA in Saudi Arabia are almost nonexistent. In this study, we aimed to assess the clinical characteristics of PsA patients and to evaluate the retention rate of various biologics in the treatment of PsA in Saudi Arabia.
| Materials and Methods | | |
Study design and data source
We conducted a retrospective observational study to assess the clinical characteristics and retention and response rates to biologic treatments according to the treating physician assessment for patients with PsA at the King Fahad Medical City, Riyadh, Saudi Arabia, during a follow-up period from 2015 to 2019.
The study included 39 patients over the age of 18 with a confirmed PsA diagnosis based on the Classification Criteria for PsA. We excluded patients who lost the follow-up or who were not on biologic therapy.
We collected data on clinical manifestations and investigations retrospectively from outpatient clinics' medical records. The data included demographics and comorbidities such as hypertension, diabetes, hypothyroidism, malignancy, hepatitis B, hepatitis C, and dyslipidemia, and psychiatric diseases clinical manifestations included peripheral-joint disease involving the knee, proximal interphalangeal (PIP) joint, distal interphalangeal (DIP) joint, metacarpophalangeal (MCP) joint, metatarsophalangeal joint (MTP), and ankle, wrist, and axial involvement.
EAMs were enthesitis, dactylitis, uveitis and the presence of inflammatory bowel disease (IBD).
The data included the use of csDMARDs, the disease duration and duration of biologic treatments (ADA, INF, ETA, CET, SEC, and UST). Moreover, we classified treatment with biologics into three lines: first-line therapy included ADA, ETA, and UST. Second-line therapy included ADA, ETA, INF, SEC, and UST. Third-line treatment included SEC, ETA INF, and UST.
We also classified the reasons for discontinuation as treatment failure, noncompliance, and adverse events.
Statistical analysis
We presented the data with descriptive statistics (mean, frequencies, and percentages). We also calculated retention rate as the percentage of patients still on a biologic treatment at specified times.
We measured time on the drug as the number of days the patient continued treatment. If the same drug was restarted within 3 months of the recorded treatment stop date with no new biologic treatment documented, we considered the treatment periods one period. In addition, we used the independent Mann–Whitney and Kruskal–Wallis tests to compare duration between medications and lines.
We analyzed all data using Statistical Package for the Social Sciences (SPSS) 25.0 (SPSS Inc., Chicago, IL, USA).
| Results | | |
We collected data from 39 patients with PsA on biologic treatment. The majority of patients were women (n = 31, 79.5%). The patients' average age was 54 years, and the median disease duration was 3 years. 92.3% of our patients developed peripheral arthritis with main involvement of the knee and PIP joints (20.5% for each) followed by DIP and MCP joints (17.9% for each), then MTP, wrists, and ankle joints (2.6% for each). Axial involvement was reported in 28.2% of our patients.
Furthermore, the comorbidities were hypothyroidism (n = 7, 17.95%), dyslipidemia (n = 7, 17.95%), and diabetes mellitus (n = 7, 17.95%), psychiatric diseases (n = 8, 20.51%), and hypertension (n = 5, 12.8%).
Malignancy manifested in one patient as breast cancer [Figure 1].
EAMs were enthesitis (15%) and dactylitis (12.5%), whereas IBD and uveitis were not noted in our patients [Figure 2].
With regard to disease-modifying antirheumatic drugs, 28 (71.8%) patients were exposed to methotrexate, of whom; 13 (46.45%) patients continued it. The mean duration of MTX use was 3.67 years. Two (5.1%) patients were given sulfasalazine and only one continued it.
We recorded the longest average duration in first-line therapy with ETA (120 weeks) and the longest duration in second-line therapy with ADA (177 weeks). On the other hand, in third-line therapy, SEC had the longest duration (244 weeks) [Table 1]. | Table 1: Retention rate of biological treatment in psoriatic arthritis patients
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76.9% of patients who discontinued ADA and switched to another treatment line were due to inefficacy, whereas 17.1% of patients discontinued SEC due to inefficacy. All patients who discontinued biological therapies due to inefficacy were due to secondary failure except one patient who discontinued ETA due to primary failure. The most adverse events were reported with SEC and ETA (7.1%). The adverse events that resulted in discontinuation of SEC were psoriatic eruption exacerbation and infections (recurrent UTI and foot infection) while in ETA, the injection site reaction was the main adverse event. Of the patients who received ADA, 15.5% discontinued the treatment due to noncompliance [Figure 3]. | Figure 3: Reasons for discontinuation or switch of biologicals therapy in PsA patients
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| Discussion | | |
In this study, we summarized the demographics, characteristics, and prevalence of comorbidities in PsA Saudi patients. We also evaluated the responses and retention rate of biologic therapy Interestingly, 79.5% of our PsA patients are women in contrast to what was known that women and men are equally affected. However, Love et al. supported our results and observed a higher ratio of women to men with PsA.[5],[14]
Our study showed that diabetes mellitus occurs in 17.95% and dyslipidemia in 18.4%, which are almost similar to what was reported previously. Feldman et al. reported DM in 15.9% of PsA patients.[15] Similarly, Husted et al. reported hyperlipidemia in 19.7% of PsA patients.[16]
In this present study, we observed high prevalence of psychiatric illnesses associated with PsA. Our findings were in line with a study conducted by Perez-Chada and Merola, who reported almost similar prevalence (20%) of depression in PsA patients.[17]
In our study, 92.3% of patients had peripheral arthritis and 28.2% had axial involvement. Similarly, axial PsA has been reported in 5%–28% of patients with early-stage disease and in 25%–70% of patients with long-standing disease.[18]
The Danish registry of 764 PsA patients who started the first TNFi showed that the drug retention rates were 70% and 57% at the 12-month and 24-month follow-ups, respectively. However, the median drug survival was 2.9 years (132 weeks).[19]
Another study conducted to evaluate the 2-year survival rates of anti-TNF-α therapy in PsA showed the persistence of ETA (68.3%) was significantly higher than that of ADA (51.9%).[20] Similarly, a large multicenter observational study of 650 psoriasis patients evaluated survival rates of anti-TNFα agents showed ETA had a more prolonged survival (mean of 51.4 months) than INF (36.8 months) and ADA (34.7 months), identical to what we found in our study in the first-line therapy.[21]
On the other hand, in a large cohort study, ADA was highly effective, and the retention rate was 86.6% at 12 months and 73.8% at 24 months, supporting our results in second-line therapy in the present study.[22] On the other hand, Gniadecki et al. reported INF had the most prolonged survival rate compared to ADA and ETA.[23],[24]
One of the most important reasons that lead to reducing the survival rate of anti-TNFα drugs is shifting to another agent with the exact mechanisms of action, where evidence has shown that the mean anti-TNFα drug survival rate is reduced significantly after shifting to another anti-TNF agent.[13]
Haddad et al. found that SEC had a longer persistence than ADA, INF, and UST, and these results support our finding that in third-line therapy, SEC had a persistence of more than 4 years.[25]
Moreover, in another study conducted to assess SEC's long-term efficacy, the authors observed sustained clinical improvements through week 104,[26] suggesting that SEC would be the best medication choice after TNFα blocker failure.
Indeed, the European Alliance of Associations for Rheumatology recommended IL-17 inhibitors such as SEC as a first-line agent alongside other biologics due to higher persistency.[27]
D'Angelo et al. reported several reasons for the discontinuation of ADA over the 24-month treatment period: primary inefficacy (7.1%), adverse events (6.1%), and loss during follow-up (9.4%). This study showed ADA was the most discontinued drug due to the lack of efficacy and patients' noncompliance.[22]
A Spanish study was conducted to evaluate the drug retention rate and safety of SEC in patients with axial spondyloarthritis and PsA showed a good retention rate in patients previously exposed to several biologic therapies. Furthermore, 59% of the discontinuations occurred due to inefficacy, and 36% occurred due to an adverse event.[28] These results are very similar to ours.
Of note, our study has some limitations; the collection of data in a retrospective manner may carry a specific risk of bias due to the lack of standardization in data collection, the sample size was relatively small, unavailability of data about psoriasis and nail involvement in our cohort, and some patients' profiles have not been completed, which led to excluding these patients, who might affect our results. Furthermore, there is no information on the patients who lost follow-ups. Importantly, we did not use specific tools to assess and determine the disease activity of PsA and response to treatments. Finally, SEC was not added to the drug formulary in KFMC until 2018. Hence, there was no fair comparison with other biologicals, despite the appearance of encouraging results for it during a short period of usage. Therefore, our findings should be interpreted with caution. To confirm these findings, a large sample size study should be conducted. To the best of our knowledge, this is the first real epidemiological and clinical characteristics study to report the characteristics of PsA patients and the retention rate of biological therapies nationally in Saudi Arabia.
Our study provides valuable data regarding the overall safety, efficacy, and survival of a drug in heterogeneous patient populations, usually with comorbidities.
| Conclusion | | |
This study provided insight into the demographics, characteristics, and responses to various biological treatments of PsA patients in Saudi Arabia. Overall discontinuation of biological agents is mainly due to secondary failure, especially with ADA. However, we found the use of SEC to be highly effective and associated with a high retention rate.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1]
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