Reducing Treatment Risks in PsA

To reduce risks while improving quality of life, a comprehensive care approach for psoriatic arthritis patients requires the recognition of treatment risks such as, renal toxicity, gastrointestinal toxicity and increased cardiovascular risk.

Specifically, all biologic therapies for psoriatic arthritis are associated with an increased risk of infection. In monitoring patients, physicians should be cognizant of the possibility of the development of serious infections that could necessitate a change in treatment.

Martin Bergman and Amy Lundholm suggest in a March 20 article in Arthritis Research & Therapy that, “The overall management of patients with PsA is complex and requires the adoption of a more patient-focused multidisciplinary approach. “

The authors point out that, “The clinical spectrum of PsA is extremely diverse in both disease severity and tissues affected, and this disorder often occurs in conjunction with several associated comorbidities.”

Compared to patients with rheumatoid arthritis, those with psoriatic arthritis do not have circulating autoantibodies and are negative when tested for rheumatoid factor. Psoriatic arthritis is associated with physical manifestations such as peripheral joint, connective tissue and axial pain and inflammation. In addition, patients are at risk for psychological manifestations such as depression.

The prevalence of psoriatic arthritis is high, 30% among patients with psoriasis, and more common in women than men. Psoriatic arthritis causes substantial reductions in the quality of life of those who suffer from it.

The authors believe that, “Mitigation of risks associated with the disease itself, its treatment, and associated comorbidities are all important considerations when managing patients with psoriatic arthritis.”

The authors have created a framework describing risk in psoriatic arthritis patients in an effort to facilitate a comprehensive approach to improving quality of life.

Physicians should strive to make prompt and accurate diagnoses. Late initiation of treatment leads to poor patient outcomes. The authors point out that, “remission in psoriatic arthritis has been attributed to early diagnosis and treatment.”

The following are the risk categories and their respective risks:

Disease related risks

• Assessment of symptoms (pain, stiffness, swelling, rash)
• Assessment of function
• Quality of life (social interaction, sexual health, body image)
• Documentation of extra-articular manifestations and/or comorbidities.
• Poor balance/risk of falls.

Treatment-related risks

• Contraindications (NSAIDs in cardiovascular disease, irritable bowel disease)
• Adverse events (liver damage with methotrexate)
• Poor compliance/persistence (reduced efficacy of biologics)
• Laboratory monitoring with biologics
• Immunogenicity with biologics

Psychosocial risks

• Mental health Evaluation (depression and anxiety)
• Alcohol abuse
• Self-esteem issues
• Social participation

The authors suggest that the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis 2015 treatment recommendations provide a guide consistent with treating-to-target in psoriatic arthritis and promote tight control of disease activity, which has been shown to improve joint outcomes.

A review of treatment options for PsA

(Source:  “Mitigation of disease- and treatment- related risks in patients with psoriatic arthritis”)

TNF inhibitors etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol have improved the signs and symptoms of PsA in clinical trials. Other therapeutics have shown varying degrees of efficacy:  apremilast (an oral phosphodiesterase-4 inhibitor), abatacept (a T cell selective co-stimulation modulator), ustekinumab (IL-12/23 inhibitor), and secukinumab (an IL-17A inhibitor).

Switching:  For patients who fail a biologic therapy, the GRAPPA guidelines provide a conditional recommendation for switching to a different biologic agent within a drug class or to a drug with a different mode of action. Recent investigations have shown that combining TNF inhibitors with a DMARD can prolong biologic persistence, “but a clear benefit of combination therapy was not observed.”

NSAIDs are effective for relieving musculoskeletal symptoms due to joint inflammation, but have no efficacy on psoriatic skin lesions and are associated with adverse events (renal toxicity, gastrointestinal toxicity, and the risk of developing CV events).

Traditional DMARDs for PsA include sulfasalazine and methotrexate. Some randomized trials have been unable to show efficacy. Methotrexate is ineffective in treating axial inflammation, however, the Methotrexate in Psoriatic Arthritis (MIPA) trial (that showed no benefit with respect to the primary endpoint of PsA response criteria), treatment with MTX resulted in a significant improvement over placebo in both patient and physician global assessments, as well as Psoriasis Area and Severity Index (PASI) scores at 6 months.

PUVA:  Treatment of skin disease associated with PsA can include phototherapy such as ultraviolet B or oral psoralen followed by ultraviolet A (PUVA). PUVA therapy carries an increased risk of skin cancer compared with other forms of ultraviolet light treatment and patients receiving this treatment should be monitored for skin cancer. 

Treat-to-Target

In SpA, remission and sustained low disease activity have been suggested as possible targets. A universal definition of the target (e.g., remission, prevention of flare of disease) has not yet been widely accepted or endorsed in SpA for treat-to-target approach.

The Tight Control of Psoriatic Arthritis (TICOPA) trial, an open-label, randomized, controlled study, suggested treat-to-target care for this group of patients. TICOPA compared treat-to-target versus standard of care in newly diagnosed PsA patients receiving methotrexate (MTX), a combination of disease-modifying antirheumatic drugs (DMARDs), or TNF inhibitors. The study demonstrated that a step-up dosing regimen was superior to standard of care. After 48 weeks, the odds of achieving ACR20 nearly doubled.

Disclosures:

No financial support was given to the authors.

Martin Bergman reports affiliations with Abbvie, Amgen, Cegene, Genentech, Horizon, Iroko, Janssen, Novartis, Pfizer, Merck, BMS, and Johnson & Johsnson.

References:

Martin Bergman and Amy Lundholm. “Mitigation of disease- and treatment- related risks in patients with psoriatic arthritis,” Arthritis Research & Therapy. Published online Mar, 20, 2017. DOI: 10.1186/s13075-017-1265-5