Introduction

Background and definition

Psoriatic arthritis (PsA) is a complex inflammatory disease characterized by both musculoskeletal and non-musculoskeletal manifestations, representing a distinct disease entity at the intersection of rheumatology and dermatology [1].

PsA is distinguished from other types of inflammatory arthritis by the fact that it is often preceded by psoriasis, observed in approximately 80% of cases [2]. The global annual incidence of PsA is 83 per 100,000 with no discernible gender predominance, and a prevalence of 133 per 100,000, reflecting consistent geographic variability [3].

Despite its importance, the Middle East and North Africa (MENA) region, including Saudi Arabia, lack adequate epidemiological data, reflecting a gap in understanding the specific characteristics of this population [4]. Within the region, managing PsA presents significant challenges due to the absence of local registries, reliable diagnostic methods, and effective reporting [4]. This has led to the misconception that PsA is relatively rare in MENA, although the actual burden remains unknown [4]. Existing insights are sporadic, arising from isolated studies [5,6,7].

The manifestations of PsA extend beyond peripheral arthritis, enthesitis, dactylitis, spondylitis, psoriatic skin, nail disease, and uveitis, encompassing the gastrointestinal system, often associated with inflammatory bowel disease (IBD) [8,9,10]. A recent study by Alunizi et. al., provided valuable insights into PsA presentation and therapeutic interventions specific to the Saudi population [7]. The study reported percentages of 92.3%, 28.2%, 15%, and 12.5% for peripheral arthritis, axial involvement, enthesitis, and dactylitis, respectively [7]. PsA patients also suffer from sleep disturbance, decreased work capacity, and social isolation [11]. These myriads of symptoms collectively impact the quality of life (QoL), inducing fatigue in 22% of patients [12]. The clinical diversity of PsA demands a multidisciplinary approach for effective management [13, 14].

The pivotal 2006 International Classification of Psoriatic Arthritis (CASPAR) study introduced standardized classification criteria for PsA [15]. Since then, additional guidelines have been developed to facilitate the management of PsA [16,17,18].

Due to the impairment of the QoL, early diagnosis and management of PsA are necessary for optimal care and good disease prognosis [19]. The management becomes more challenging in the MENA region due to the limited knowledge and awareness of this disease entity [4]. Consequently, the development of a specific guideline tailored to the Saudi Arabian population becomes imperative for addressing these challenges and enhancing PsA care in the region.

Purpose, aim, and scope

In Saudi Arabia, there is a lack of unified national consensus on the optimal management of PsA. As a result, there is often a debate among healthcare providers about how to make clinical decisions when managing the disease, which can result in either over-prescribing or under-prescribing biological agents. Al Rayes, et al.’s recently published consensus-based recommendations addressed the aspects of diagnosis, referral and clinical management of patients with PSA [20]. Therefore, this paper aims to deliver evidence-based consensus recommendations for the optimal use and monitoring of biological therapy in managing PsA. Due consideration was given to the specific characteristics of the patient population in Saudi Arabia. These recommendations are intended to aid physicians in managing their patients and should therefore be viewed as informative rather than prescriptive.

Target population, audience/end-users

The target population for the present consensus document are people in Saudi Arabia with PsA. This consensus statement is for rheumatologists, dermatologists, and other healthcare providers involved in managing people with PsA in the secondary care setting.

Materials & methods

A multidisciplinary work group consisting of two dermatologists, six rheumatologists, and five pharmacists were convened by the Saudi Ministry of Health (MOH) based on their expertise in managing PsA. Throughout the process of developing the consensus recommendations, one method expert was invited and consulted. Over a period of four months (December 2021 – March 2022), five in-person consensus workshops were conducted to accomplish three main objectives: 1) discuss the need for national consensus recommendations for PsA management, 2) review existing international guidelines, and 3) create recommendations suitable for the Saudi context.

Before the first workshop, a literature search was conducted using PubMed to identify relevant articles on PsA guidelines. Based on their reputation and relevance, three international guidelines were chosen as the starting point for developing the current recommendations: The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the European Alliance of Associations for Rheumatology (EULAR) and the British Society of Rheumatology (BSR) guidelines [16, 21,22,23,24,25,26]. To ensure the recommendations were based on the latest evidence, the reference lists of these guidelines were evaluated and additional articles on emerging evidence were sought.

The workgroup assigned tasks to its members to develop evidence-based recommendations on various PsA management topics, taking into considering both the evidence and its applicability to real-world practice. During the workshops, a modified Nominal Group Technique (NGT) was used to reach agreements on the recommendations [27]. The NGT was chosen as the consensus methodology as it is a well-established and formal process that ensures a fair, inclusive, and rigorous consensus development process [27]. It allows for the integration of diverse perspectives and expertise, which was important given the multidisciplinary nature of the work group [27]. A recommendation was considered agreed upon if at least 75% of the members voted in favor. The strength of the recommendations was not indicated. A draft document containing all the consensus recommendations was compiled and shared with the expert workgroup and MOH experts for a 30-day feedback period. During the final workshop, the received comments were discussed, and further agreements were reached.

Results

Eligibility criteria for biological treatment

The following criteria are accepted as appropriate for initiating therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKi) [16, 28,29,30,31,32,33,34,35,36,37,38,39]:

  1. 1.

    Peripheral arthritis: patients who have failed, developed side effects, or have contraindications to conventional DMARDs.

  2. 2.

    Axial PsA: patients who have failed, developed side effects, or have contraindications to non-steroidal anti-inflammatory drugs (NSAIDs) treatment.

  3. 3.

    Enthesitis and dactylitis: patients who have failed, developed side effects, or have contraindications to NSAIDs treatment.

Monitoring for disease activity and assessment tools

Patients with PsA should be monitored regularly to assess the degree of disease activity and the need for therapy adjustment [16]. It is recommended to monitor patients with active disease more often, ranging from monthly to every three months. However, the data is lacking regarding the best interval for monitoring [23].

It has been suggested to use a treat-to-target (T2T) approach for patients treated for PsA, in which treatment is adjusted at frequent periods if the treatment goal, defined as inactive disease or minimal disease activity (MDA), was not met [16].

The best tool to monitor disease activity is not established. However, monitoring patients with PsA should focus on patient-reported measures and cover all domains of the disease; peripheral arthritis, axial disease, enthesitis, and dactylitis by comprehensive history and physical examination. Moreover, assessment should be supplemented with appropriate laboratory tests and imaging studies [22, 23]. Validated and quantified measurements should be considered when considering the use of assessment tools. Multiple validated assessment tools are available for patients with PsA [40]. Examples of available measurements are Disease Activity Index for Psoriatic Arthritis (DAPSA); minimal disease activity criteria (MDA); Disease Activity Score (DAS and DAS 28); the Simplified Disease Activity Index (SDAI); the Clinical Disease Activity Index (CDAI); Composite Psoriatic Disease Activity Index (CPDAI); and the Psoriatic Arthritis Disease Activity Score (PASDAS) [23, 40].

In peripheral arthritis, we recommend using either DAPSA or MDA as tools for disease activity monitoring in patients since both support T2T management in PsA [40].

DAPSA score is calculated by the sum of the following:

  • swollen joint count of 66 joints,

  • tender joint count of 68 joints,

  • patient’s global assessment on a 10 cm visual analogue score (VAS) (in cm): (0 for not active, up to 10 for very active)

  • patient’s pain score on a 10 cm VAS (in cm): (0 for none up to 10 for very severe), and

  • CRP (mg/dL).

On the other hand, a patient is classified as achieving MDA when meeting 5 of the 7 criteria shown in Table 1. Moreover, patients can be further classified as achieving very low disease activity (VLDA) when they meet all the criteria [40]. The interpretation of DAPSA scores and MDA criteria for PsA are shown in Table 1 [40].

Table 1 Interpretation of Disease Activity Index for Psoriatic Arthritis scores and Minimal Disease Activity criteria for psoriatic arthritis
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In patients with axial disease, disease activity assessment with measures used for axial spondylarthritis is recommended [23, 41]. Examples of commonly used measures in axial spondylarthritis are the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) [41,42,43]. For the purposes of these consensus recommendations, the ASDAS tool is utilized as it combines acute phase reactants and patient- reported outcomes. The ASDAS disease activity score is classified as shown in Fig. 1 [44].

Fig. 1
figure 1

Ankylosing Spondylitis Disease Activity Score

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The recently updated T2T recommendations propose at least 50% improvement of the composite measure within 3 months and target achievement within 6 months from therapy initiation. Therefore, it is recommended to use a continuous measure of disease activity to follow patients longitudinally and reflect their perceptions [16].

Treatment goals

The main goal of therapy in all patients with PsA is to achieve the target of remission, or alternatively, low disease activity in all disease domains and improve QoL [16, 22, 23].

Any of the following criteria should be achieved for the treatment goal of PsA:

  1. 1.

    Peripheral arthritis: at least 50% improvement of the DAPSA score within 3 months and reaching the target within 6 months from therapy initiation by either achieving complete remission (DAPSA ≤ 4) or low disease activity (DAPSA > 4 and ≤ 14) [45].

  2. 2.

    Axial PsA: a change of 1.1 or more in the ASDAS score within 3 months and reaching the target within 6 months from therapy initiation by either achieving complete remission (ASDAS < 1.3) or low disease activity (ASDAS < 2.1) [42, 46].

  3. 3.

    Enthesitis and dactylitis: meeting at least 5 of the 7 MDA criteria within 6 months from therapy initiation [45].

Screening, precautions, and monitoring of biologics

Baseline assessment should include complete blood count (CBC), liver enzymes test (alanine transaminase (ALT), aspartate aminotransferase (AST)), creatinine, serum albumin, hepatitis B and C serology, tuberculin skin test (TST) or interferon-gamma release assay (IGRA) as appropriate, and a chest X-ray (Table 2) [47,48,49,50,51,52,53,54,55,56]. Hepatitis B serology includes HBsAg, HBcAb, and HBsAb [50]. HIV screening is recommended for high-risk group patients [53]. Patients initiated on JAKi should have a baseline lipid profile including total cholesterol (TC), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) [52].

Table 2 Baseline screening before initiation of bDMARDs and JAKi therapy
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Screening for Tuberculosis (TB)

The use of bDMARDs and JAKi therapy is associated with a higher likelihood of developing active TB and experiencing reactivation of latent TB, making it imperative to conduct screening for both active and latent TB before starting the treatment [53, 54]. The risk is higher with tumor necrosis factor inhibitors (TNFi) treatment than with other bDMARDs [53]. The screening for TB should include a chest X-ray and either TST or IGRA. Immunocompromised patients have lower sensitivity and specificity for TST, and to a lesser extent, IGRA test [55, 56]. Therefore, it is recommended to do both TST and IGRA tests in immunocompromised patients [57]. A patient with a positive TST or IGRA test should be diagnosed with latent TB and treated accordingly [57].

bDMARDs and JAKi therapies for the treatment of severe PsA

Table 3 lists all bDMARDs and JAKi therapies that are currently registered and approved by the Saudi Food and Drug Authority (SFDA) for the treatment of severe PsA. It provides a summary of the dosing scheme (loading and maintenance), evaluation of the efficacy, and half-life [34, 38, 58,59,60,61,62,63,64,65,66,67,68,69,70,71].

Table 3 bDMARDs and JAKi therapies available in Saudi Arabia for the treatment of psoriatic arthritis, dosing scheme, efficacy, and half-life
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Treatment algorithm

Figure 2 represents the treatment algorithm proposed for the management of the following domains of PsA: peripheral arthritis, dactylitis, enthesitis, and axial PsA.

Fig. 2
figure 2

Treatment algorithm for the management of psoriatic arthritis

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Peripheral arthritis

The treatment choice in patients with peripheral arthritis should be based on poor prognostic factors [28]. In the absence of poor prognostic factors, patients can be treated with NSAIDs [29]. If disease activity persists after four weeks of NSAIDs treatment, DMARDs should be initiated with methotrexate (MTX) being the preferred choice [30]. However, leflunomide can also be used [30]. Patients with one or more poor prognostic factors should start with MTX as the first line of treatment [30]. Poor prognostic factors include polyarthritis, joint damage, high sedimentation rate or CRP, and clinically relevant extra-articular features [72].

In patients with inadequate response or intolerance to NSAIDs and MTX, treatment with bDMARDs and JAKi is recommended [16]. Inadequate response to treatment is defined as a lack of symptom improvement within three months (50% or greater reduction in the DAPSA), or failure to achieve treatment target after six months (low disease activity or complete remission). Patients with inadequate treatment response to conventional DMARDs should be started on interleukin 17 inhibitors (IL-17i) [31, 32]. This recommendation is supported by research indicating that IL-17i optimize more disease domains, provide better skin responses, and demonstrate effective musculoskeletal efficacy in patients with skin psoriasis [73]. IL-17i also have better persistence and fewer safety concerns compared to TNFi [73]. Patients with inadequate response to treatment with IL-17i should be switched to JAKi, as the SELECT-PSA trial has shown that JAKi are superior to TNFi [36, 37]. Patients with inadequate response to IL-17i and JAKi can be started on IL-23i or TNFi [33,34,35]. The recommendation to prioritize IL-23i after inadequate response to IL-17i and JAKi is based on limited clinical practice experience in Saudi Arabia at present.

Phosphodiesterase 4 (PDE4) inhibitor is recommended for patients with mild peripheral arthritis who have failed conventional DMARDs and have a contraindication or intolerance to bDMARDs or JAKi [39]. Mild peripheral arthritis is defined as oligoarthritis or low disease activity by composite scores (DAPSA > 4–14).

Dactylitis and enthesitis

In patients with enthesitis and dactylitis, it is recommended to begin treatment with NSAIDs [16, 38]. IL-17i are recommended for patients with persistent enthesitis/dactylitis symptoms or intolerance to NSAIDs [31, 32]. Patients with inadequate response to IL-17i should be switched to IL-23i [33, 34, 74]. Patients with inadequate response to IL-23i can be switched to JAKi and TNFi, due to the shorter retention rate of TNFi [35,36,37].

Axial PsA

In patients with axial disease, we recommend using NSAID as the first line of treatment [16]. For patients with an inadequate response (ASDAS ≥ 2.1) within 4–12 weeks of treatment or have side effects or contraindications to NSAIDs treatment, IL-17i should be started [31, 32]. This is because IL-17i has shown efficacy in treating axial PsA in a randomized controlled trial (RCT), whereas there is current no RCT data available for TNFi in axial PsA [75]. If patient symptoms do not improve after three months of treatment (decrease of ≥ 1.1 points on ASDAS) or do not achieve the treatment target at six months (ASDAS < 2.1), we recommend switching to a TNFi. JAKi or IL-23i can be used if the patient fails TNFi treatment [33, 34, 36, 37].

Recommendations for the treatment of PsA with biological therapies

Adjusting/maintenance biological therapy

In patients with a well-controlled disease, there is insufficient consensus on whether their bDMARDs dose should be maintained, tapered, or discontinued altogether. There are limited data suggesting a particular risk of relapse with treatment tapering [76,77,78,79,80,81]. Therefore, physicians should explain the risk of relapse to the patient before tapering their medications. Tapering the treatment is considered appropriate for patients with the following criteria [16]: complete remission of peripheral arthritis (DAPSA ≤ 4), complete remission of axial PsA (ASDAS < 1.3), absence of extra-articular features, at least six consecutive months of complete remission, and normal acute phase reactants.

The total dose can be initially reduced by 20–50% by either decreasing the dose or increasing the dosing interval [81, 82]. Following tapering, the patient should be evaluated after eight weeks. If the patient remains in remission, follow-up visits may be scheduled every 12–16 weeks. Patients can contact the clinic coordinator for an early appointment if they feel their disease activity increases. Disease activity should be assessed every visit through clinical examination and inflammatory markers. Imaging studies can be utilized for further evaluation [83]. When remission is lost, the bDMARDs should be restored to the previous dose. Corticosteroids or NSAIDs can be used for symptomatic relief during this period.

Combination

There is little evidence that combining MTX with bDMARDs improves the efficacy of bDMARDs in PsA patients. However, some data suggest that combining MTX with TNFi is beneficial in terms of treatment maintenance and level of response, especially in patients using monoclonal antibodies [84, 85].

Biologic therapy discontinuation

Discontinuation of bDMARDs is not recommended as it is almost always associated with disease relapse [16, 78,79,80,81]. There are certain factors that can predict if loss of remission after discontinuing treatment, such as high disease activity, smoking, male gender, skin involvement, and synovial hypertrophy [81]. However, patient preference for stopping the medication should be acknowledged. If a patient is undergoing tapering, bDMARD discontinuation may be considered if they are at a minimal dose, have achieved the therapeutic goal for 6–12 months after the last dosage decrease, and there is no evidence of significant radiographic progression or active disease on ultrasound [82].

The minimal tapered dose is defined as 25% of the medication dose shown in the summary of product characteristics (SPC) [82]. Once the bDMARD is discontinued, the patient should be monitored closely by the physician.

Management of inadequate response

Switching therapy among patients who have failed a biological agent should preferably be to another agent with a different mechanism of action. Evidence has shown that the mean TNFi survival rate is reduced significantly after shifting to another TNFi agent (first TNFi 2.2 years, second TNFi 1.3 years and third TNFi 1.1 years) [86]. Moreover, an abstract published in EULAR 2021 indicates that if patients failed secukinumab and then shifted to ixekizumab (both agents are IL-17i), 65% will fail after a median time of eight months [87]. There were no head-to-head trials evaluating the best agents to be used in such patients’ population. This offers flexibility for the clinician to choose from the agents. Comorbidities, extra-articular manifestations, and active disease domains should be taken into consideration during the switching process, while some biological agents could be contraindicated or less/non-effective as compared with others. Moreover, a patient-centered approach could assist in selecting the agent, such as the preference of oral route or frequency of injections.

Use of bDMARDs and JAKi in special patient populations

With the increased introduction of biologics in PsA management, reaching disease remission is becoming a possible and desirable goal. Despite their efficacy in PsA, biologics carry some risks that clinicians should be aware of, especially in patients with special situations or comorbidities [47, 88].

Table 4 presents recommendations for treatment choices for people with the following comorbidities: infection, TB, HBV, HCV, HIV, malignancy, cardiovascular diseases, respiratory diseases, uveitis, demyelinating disease, connective tissue diseases, obesity, patients undergoing surgery, and IBD. It also covers the choice of therapy in pediatrics and adolescents, and pregnant and lactating women [16, 21, 23, 47, 53, 72, 76, 88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135,136,137,138,139,140,141,142,143].

Table 4 Use of bDMARDs and JAKi in special patient populations
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Conclusion

In conclusion, these evidence-based consensus recommendations offer valuable guidance for the management of PsA in Saudi Arabia. They are rooted in the most up-to-date evidence and global consensus statements. The recommendations emphasize the importance of involving patients in shared decision-making and adopting a patient-centered approach to care. They also highlight the rational use of medications and advocate for a step-care approach in treatment, along with more frequent monitoring of active disease. Additionally, it is important for the treating physician to review the properties of SFDA-approved biologic agents, such as their efficacy, half-life, dosing scheme, and patient preference, before selecting a treatment option treatment selection. As more research develops, these recommendations may be subject to amendment and adjustment.