Psoriatic arthritis (PsA) is a severe, heterogeneous, systemic rheumatic disease characterised by inflammation of the joints, periarticular structures and skin and its appendages, manifested as psoriasis. Musculoskeletal involvement may involve different domains including peripheral arthritis, axial involvement, enthesitis and dactylitis1. Dermatological involvement includes the skin and nails.

The heterogeneity of PsA means treatment must be personalised considering each patient’s involvement in each domain: peripheral arthritis, axial involvement, enthesitis, dactylitis, skin and nails. This individualisation is now more important because the efficacy of the different treatments is heterogeneous between domains, therefore, treatment may be suboptimal if it does not consider the profile of the patient's condition.

PsA affects other systems in addition to the skin and joints. The disease, especially in the active stages, induces a state of systemic imbalance, characterised by metabolic syndrome and a significant increase in cardiovascular morbidity. Therefore, appropriate treatment of the inflammatory process becomes a strategy to minimise the impact of the disease.

Treatment of PsA usually starts with non-steroidal anti-inflammatory drugs (NSAIDs) and also includes conventional synthetic disease-modifying drugs (csDMARDs), target-specific disease-modifying drugs (tsDMARDs) including Janus kinase (tofacitinib) and phosphodiesterase-4 (apremilast) inhibitors, as well as biological disease-modifying drugs (bDMARDs), including tumour necrosis factor antagonist agents (TNF-I), interleukin (IL) 12/23 antagonist (ustekinumab), IL-17 (secukinumab and ixekizumab), and IL-23 (guselkumab), and abatacept (CTLA-4 fusion protein), which is a T-cell co-stimulation inhibitor.

These broadened therapeutic options offer patients new possibilities in the control of their disease, but also force us to rethink strategies in selecting the different treatments, assessing the efficacy of each of the agents for specific manifestations of PsA and, where possible, establishing an order in prescribing them. These recommendations aim to optimise the treatment of patients with PsA based on the available scientific evidence and using expert criteria in their management.

The recommendations consider the PsA disease domains proposed by the GRAPPA2 group as a starting point for defining the usefulness of different therapeutic agents. These recommendations are endorsed by the Mexican College of Rheumatology.

Executive committee: An executive committee (EC) was formed that comprised the principal investigators, a project coordinator and two members.

The functions of the EC included the planning and execution of the project, the selection of the members of the expert group, the scheduling and logistics of the meetings and the selection of the personnel in charge of the literature review, and its methodology.

Expert group. A group was formed of 16 rheumatologists and three dermatologists with knowledge and experience in the treatment of patients with PsA and with experience in therapeutic recommendations and guidelines. The functions of the expert group were to select the themes and subthemes in relation to the definition and classification of PsA, to develop the research questions used in the systematic literature review (SLR) considering the six disease domains of PsA, to choose the primary and secondary outcome measures, to prepare the work agendas and, finally, to draft the recommendations.

Systemic literature review. As a prerequisite to the consensus session, two independent investigators conducted an SLR on treatments for PsA. The full methodological description of the SLR is presented in Appendix B, Supplementary data.

The SLR included research questions broken down by disease domain: peripheral arthritis, axial disease, dactylitis, enthesitis, skin psoriasis and nail psoriasis (Ps). For each domain, the following questions were asked: inflammatory activity, structural impairment, improvement, partial remission, inactive disease, moderate activity, high activity, very high activity, significant clinical improvement, very significant clinical improvement, quality of life and health status. It was complemented by the safety and efficacy of pharmacological, non-pharmacological and surgical treatments considered in the SLR. The SLR included articles published in English and Spanish.

The Patient or problem, Intervention, Comparison, Outcomes (PICO) question was used to establish the search criteria, with the following criteria:

Patients. Patients with a diagnosis of PsA with disease onset ≥18 years of age.

Intervention. Pharmacological therapy (bDMARDs, csDMARDs, NSAIDs, glucocorticoids, other), non-pharmacological therapy (exercise and information programmes) and surgical intervention.

Comparison. The different interventions mentioned above were evaluated in various regimens or doses, compared to another intervention, placebo, or none.

Outcomes. The most used outcome measures were used in each of the domains analysed.

In peripheral arthritis, the American College of Rheumatology improvement response criteria (ACR) indices for 20%, 50% and 70% improvement (ACR20, ACR50, ACR70) and the Disease Activity Score for 28 Joints (DAS-28) were used. In axial disease, the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI), the improvement criteria ASAS 20, ASAS 40, ASAS 5/6, ASAS partial remission (ASAS-PR), pain, C-reactive protein (CRP), as well as the radiographic indices Bath Ankylosing Spondylitis Radiology Index (BASRI), modified Stoke Ankylosing Spondylitis Spine Score (mSASS) and Radiographic AS Spinal Score (RASSS) and MRI-based indices (Leeds, Berlin, Spondyloarthritis Research Consortium of Canada [SPARCC Scoring system]) were used.

The outcome measures considered for enthesitis were change from baseline in the enthesitis score, the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), the Leeds Enthesitis Index (LEI), the Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC) and the resolution rate of enthesitis cases.

The Leeds Dactylitis Index-Basic (LDI-B), the resolution rate of dactylitis cases, and change from baseline in the Dactylitis Severity Score (DSS) were considered for dactylitis.

The Psoriasis Area Severity Index (PASI) with 50%, 75%, 90% and 100% improvement (PASI50/75/90/90/100), Body Surface Area (BSA) and the Physician's Global Assessment (PGA) response indicator were considered as outcome measures) were used for psoriasis.

Studies reporting the Nail Psoriasis Severity Index (NAPSI) and the modified Nail Psoriasis Severity Index (mNAPSI) were analysed for nail Ps.

The frequency of serious adverse events, infection, serious infection, malignancy, and discontinuation of treatment due to adverse events were evaluated to assess the safety of the treatments (Appendix B, Supplementary data).

The SLR covered the period from January 2016 to June 2020, and pivotal studies of drugs with an indication in PsA were reviewed if they had been previously published. Eligible studies were meta-analyses, systematic reviews, randomised controlled clinical trials, controlled clinical trials and extension clinical trials. The search strategies were replicated in the PubMed, EMBASE, ScienceDirect and CINAHL databases, considering the characteristics and limitations of each information system.

The level of evidence of the articles was rated with the GRADE scale, according to the risk of bias, consistency, direct results, heterogeneity, precision, and publication bias.

Consensus meeting

At the second meeting, the papers reviewed in the SLR were presented, emphasising the efficacy and safety results of each study. In addition, the recommendations, and guidelines for the treatment of PsA (GRAPPA, EULAR and SER) were reviewed in detail to gain an overview of contemporary therapeutic concepts.

The evidence from the SLR was analysed in a structured way and the consensus coordinator presented the associated themes and subthemes to the committee. The proposals for each recommendation were generated from an internal discussion that took each of the disease domains as its structure. The experts gave their opinion on each proposed recommendation, and in cases of disagreement, specific aspects of the SLR were reviewed in more detail.

Prevalence of PsA

The prevalence of PsA or Ps in the Mexican population is unknown. The prevalence of psoriasis varies in different ethnicities and geographical areas. A prevalence of 2.8% has been reported in the Faroe Islands, 1.4% in Sweden and it was 1.3% in the U.S. Black population and 3.15% in the general population3. The prevalence of PsA ranges from one case (in Japan) to 420 cases (in Italy) per 100,000 population (with a mean of 180 cases per 100,000 population) and it is estimated that about 30% of patients with psoriasis develop some form of arthritis4.

A study conducted in Argentina, which examined records of 138,288 private health insurance clients from 2000 to 2006, estimated a prevalence of 74 cases per 100,000 population (95% CI, 57–94)5.

Analysis broken down by geographical area of patients with psoriasis indicates that the prevalence of PsA in Europeans was 22.7% (95% CI, 20.6%–25.0%), in South Americans 21.5% (95% CI, 15.4%–28.2%), in North Americans 19.5% (95% CI, 17.1%–22.1%), in Africans 15.5% (95% CI, .009%–51.5%) and in Asians 14.0% (95% CI, 11.7%–16.3%)6. Hence the importance of conducting epidemiological studies in our country’s population to define the real impact of the disease more accurately.

Therapeutic aspects and recommendations

Algorithms for the treatment of the musculoskeletal manifestations of PsA recommend starting treatment with non-steroidal anti-inflammatory drugs (NSAIDs)7. If there is no response or toxicity, a change to methotrexate (MTX), leflunomide (LEF) or sulfasalazine (SSZ) is recommended (csDMARDs), although efficacy varies and patients with axial disease have poor response rates. Fig. 1 shows the treatment algorithm proposed in this consensus.

Fig. 1.

Treatment algorithm for psoriatic arthritis.

Anti-TNF; bDMARDs: biological disease-modifying drugs; IL-12/23, IL-17: tumour necrosis factor inhibitors; interleukins 12,23, or 17; LEF: leflunomide; MTX: methotrexate; NSAIDs: non-steroidal anti-inflammatory drugs; PDE4: apremilast; Tofa: tofacitinib.

Each patient’s pattern of involvement in each disease domain must be considered in designing the therapeutic strategy.

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In resistant cases of PsA bDMARDs are necessary8–10. The GRAPPA guidelines do not clearly indicate a preference for the use of bDMARDs as first-line therapy, while the EULAR guidelines do consider TNF-I agents as an initial line of therapy for patients who fail with csDMARDs and with predominantly peripheral or early-stage axial disease8,9,11. Not all bDMARD therapy is successful; some patients fail to achieve or maintain a satisfactory status for a variety of reasons. We discuss the different treatments available for PsA below.

Apremilast is a tsDMARD, phosphodiesterase-4 inhibitor, used in doses of up to 60 mg per day. It has an acceptable safety profile, hence its use in PsA patients with several comorbidities. The results of apremilast therapy can be seen after four months. Combination with biological drugs is not recommended47–49. The PALACE studies consist of three phases, with reports at week 16, 28, and 52, and a four-year extension phase (open phase), in a series of three publications they reported the results of studies with the same design: randomised, placebo-controlled clinical trials to demonstrate the efficacy of apremilast at doses of 20 and 30 mg orally twice daily in 1493 patients with active PsA and a history of failure with tsDMARDs.

At week 260, 67.2% of patients had achieved ACR 20 response, 44.4% and 27.4% ACR 50 and ACR 70 response, respectively. For enthesitis and dactylitis, 62.4% had a MASES index of 0 and 80.9% had a dactylitis count of 0. Skin response in patients with more than 3% involvement of body surface area recorded a PASI75 response in 43.6% of cases.

General aspects of treatment:

In the opinion of the expert group, the following were defined as general principles for the treatment of patients with PsA:

• 1

  Treatment should be defined by mutual agreement between the doctor and the patient, after providing the patient with the information for them to make their own judgement.

• 2

  Treatment should be started from the earliest stages of the disease.

• 3

  Treatment should be provided by the specialist physician, the rheumatologist, for musculoskeletal manifestations and it is advisable for the dermatologist to be involved in the management of skin disorders in severe cases from the initial diagnosis, or in those refractory to treatment at any stage.

• 4

  Treatment is aimed at reducing the symptoms of the disease in the affected domains, improving the patient's functionality, preventing structural damage and loss of function. The objective should be clinical remission or, if this is not possible, a low degree of disease activity. There are different validated instruments for each disease domain, however, the concept of the therapeutic goal achieved did not reach unanimous consensus. The definition of improvement in each domain should preferably be based on the use of validated instruments.

• 5

  Treatment should be tailored to the patient, the domains that the disease affects in each patient need to be identified, the domain that most impacts the patient's wellbeing should be selected, and the drugs that achieve control should be selected based on this.

• 6

  The patient should be re-assessed periodically to achieve closer control of their disease activity.

• 7

  Treatment includes the detection and appropriate management of comorbidities.

The Mexican College of Rheumatology generated these recommendations through the consensus effort of a group of experts in the clinical aspects, assessment, and treatment of PsA.

The group included dermatologists as well as rheumatologists to refine treatment recommendations for PsA and nail disease and to jointly define treatment for the different manifestations, and to address general aspects of care and share perspectives on delayed diagnosis and the barriers to access to different aspects of their medical care.

Where possible, the recommendations were generated based on evidence from an SLR updated as of 30 June 2020, but considering the clinical experience of experts and the characteristics of the Mexican health system. The evidence was rated using the GRADE system. In several recommendations, the evidence is strong, and the recommendations are well-supported. This is even clearer for the use of new therapies that underwent rigorous trials in their approval process; these trials clearly define the scope of usefulness of each of the treatments.

We considered the six main domains of PsA and sought evidence to update the recommendations. However, and in line with more recent recommendations, we consider that enthesitis, dactylitis and nail involvement are unlikely to guide the choice of treatment in the earliest stages and their importance is highlighted in cases where these manifestations are refractory, to consider a secondary adjustment.

NSAIDs were included in these recommendations as a starting point in all four musculoskeletal domains. In the case of peripheral arthritis and enthesitis, the use of cDMARDs and in the case of resistance, starting bDMARDs or tsDMARDs. The use of the latter two treatment groups requires special consideration as access to them is restricted by the medical coverage for a significant proportion of our population. This requires strategies to be optimised prior to starting biological therapy. Fortunately, peripheral arthritis is the most common presentation seen in Mexico and this means several cDMARDs can be used as initial treatment.

Axial involvement in NSAID-resistant cases limits treatment with bDMARDs to only two cytokines, TNF-I, and I-IL-17. Although there is evidence of a favourable effect of tofacitinib and filgotinib in axial spondyloarthritis, we cannot recommend them from the currently available information. Ustekinumab is not considered an effective treatment in axial disease because it has not demonstrated an effect in axial spondyloarthritis trials other than in patients with PsA and axial disease. Recently, however, differences have been established between the axial involvement of axial spondyloarthritis and that of PsA76. Therefore, further evaluation of the effect on axial involvement in patients with PsA treated primarily for peripheral involvement would be desirable, as there is a possibility that a drug that does not prove useful in axial spondyloarthritis not associated with psoriasis may be useful in the axial involvement of PsA.

In contrast to axial involvement, new treatment options have emerged for the remaining PsA domains. New bDMARDs have been licensed and there is evidence to support the high efficacy of ustekinumab, I-IL-17, I-IL-23, tsDMARDs in peripheral arthritis, enthesitis and dactylitis, as well as in skin manifestations and nail disease. The experience of Mexican rheumatologists with the use of local glucorticoids to infiltrate the entheses, in dactylitis or nail beds is poor and is not recommended in our population.

In our population access to the Mexican health system is heterogeneous, which is an element to be considered. There is diverse coverage, and this restricts access to some drugs for certain populations; several public health systems provide access to some bDMARDs and tsDMARDs but in differing regimens that do not necessarily include all the drugs in each group. However, all the drugs listed in these recommendations are indicated in PsA by our regulatory agency (COFEPRIS) and are available in private care. The absence of some of the drugs mentioned here in a specific list of essential drugs provided by state insurance will require treating physicians to select viable alternatives to meet the needs of patients in their specific setting. To this end, the relative redundancy in the effect of various groups of drugs is fortunate as it opens a diversity of strategies for the initial treatment and management of refractory cases.

Novartis Mexico covered the costs of the meetings, without intervening in the discussions or the proposals made by the participating physicians.

J. Casasola-Vargas: Abbvie, Janssen, UCB, Novartis; D. Flores-Alvarado: Janssen, UCB, Novartis, Abbvie, Roche; Luis H. Silveira, Jannsen; G. Reyes-Cordero: Novartis, Eli-Lilly, Abbvie, Pfizer, UCB, Gilead; G. Villanueva Quintero, Mario Amaya Guerra: Abbvie, Celgene, Janssen, Isdin, Leo, Lilly, Novartis. Pfizer, Sanofi; B.E. Zazueta Montiel: Novartis, Eli Lilly, Roche, Amgen, UCB; A. Mendoza-Fuentes: Novartis, Abbvie; A. López Rodriguez: Novartis, Janssen, Eli Lilly; R. Burgos-Vargas: Novartis, UCB, Abbvie; C. Pacheco-Tena: Pfizer, Abbvie, R-Pharm, AstraZeneca, UCB, Janssen, Merck-Serono, Sanofi, Eli-Lilly, Novartis, Gilead.