In the JournalsPerspective

Methotrexate more effective in patients with psoriasis without PsA

Although methotrexate is generally well-tolerated and efficacious in the treatment of psoriasis, it is even more effective, with fewer reported adverse effects, among patients with psoriasis but without psoriatic arthritis, compared with those with both, according data published in JAMA Dermatology.

“Methotrexate has been used as a first-line treatment for moderate to severe psoriasis for more than 50 years,” Kexiang Yan, MD, PhD, of Huashan Hospital at Fudan University in Shanghai, and colleagues wrote. “To our knowledge, a prospective, comparative study of the efficacy and adverse effects of methotrexate in Chinese patients with psoriasis with and without psoriatic arthritis has not yet been performed.”

To determine the effectiveness and safety of methotrexate in patients with psoriasis but without PsA, Yan and colleagues conducted a prospective, single-arm, interventional study of patients at Fudan University’s Huashan Hospital. From April 1, 2015, to Dec. 31, 2017, the researchers enrolled 235 patients with psoriasis who were treated with methotrexate, including 128 with PsA and 107 without.

The initial oral methotrexate regimen was 7.5 mg to 10 mg once weekly, which, based on the patients’ clinical response, was increased by 2.5 mg every 2 to 4 weeks, to a maximum of 15 mg weekly. The intervention course lasted 12 weeks. The primary outcomes included changes in disease severity, adverse events, blood cell counts, and liver and renal function.

According to the researchers, 3.1% of patients with PsA achieved 90% reductions from baseline Psoriasis Area Severity Index scores by week 8, compared with 11.2% those without psoriatic arthritis (P=.02). By week 12, 14.8% of patients in the PsA group had achieved 90% reductions, compared with 25.2% of those without (P=.049). In addition, incidence rates of adverse events were significantly higher in patients with PsA than in those with psoriasis only.

Regarding adverse effects, 9.4% of patients with PsA experienced dizziness compared with 0.9% of those with psoriasis only (P=.007). In addition, 25% of those with PsA demonstrated gastrointestinal symptoms compared with 12.1% without (P=.01), while 26.6% had hepatoxicity compared with 15% in the psoriasis-only group (P=.04).

“Our study demonstrated that methotrexate was well tolerated by Chinese outpatients with psoriasis,” Yan and colleagues wrote. “Methotrexate appeared to be more effective and had fewer adverse effects in patients without psoriatic arthritis compared with those with psoriatic arthritis. Although multicenter trials with larger sample size are needed to confirm these results, our findings suggest that methotrexate can be recommended as first-line treatment for psoriasis without arthritis.” – by Jason Laday

Disclosure: Yan reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Although methotrexate is generally well-tolerated and efficacious in the treatment of psoriasis, it is even more effective, with fewer reported adverse effects, among patients with psoriasis but without psoriatic arthritis, compared with those with both, according data published in JAMA Dermatology.

“Methotrexate has been used as a first-line treatment for moderate to severe psoriasis for more than 50 years,” Kexiang Yan, MD, PhD, of Huashan Hospital at Fudan University in Shanghai, and colleagues wrote. “To our knowledge, a prospective, comparative study of the efficacy and adverse effects of methotrexate in Chinese patients with psoriasis with and without psoriatic arthritis has not yet been performed.”

To determine the effectiveness and safety of methotrexate in patients with psoriasis but without PsA, Yan and colleagues conducted a prospective, single-arm, interventional study of patients at Fudan University’s Huashan Hospital. From April 1, 2015, to Dec. 31, 2017, the researchers enrolled 235 patients with psoriasis who were treated with methotrexate, including 128 with PsA and 107 without.

The initial oral methotrexate regimen was 7.5 mg to 10 mg once weekly, which, based on the patients’ clinical response, was increased by 2.5 mg every 2 to 4 weeks, to a maximum of 15 mg weekly. The intervention course lasted 12 weeks. The primary outcomes included changes in disease severity, adverse events, blood cell counts, and liver and renal function.

According to the researchers, 3.1% of patients with PsA achieved 90% reductions from baseline Psoriasis Area Severity Index scores by week 8, compared with 11.2% those without psoriatic arthritis (P=.02). By week 12, 14.8% of patients in the PsA group had achieved 90% reductions, compared with 25.2% of those without (P=.049). In addition, incidence rates of adverse events were significantly higher in patients with PsA than in those with psoriasis only.

Regarding adverse effects, 9.4% of patients with PsA experienced dizziness compared with 0.9% of those with psoriasis only (P=.007). In addition, 25% of those with PsA demonstrated gastrointestinal symptoms compared with 12.1% without (P=.01), while 26.6% had hepatoxicity compared with 15% in the psoriasis-only group (P=.04).

“Our study demonstrated that methotrexate was well tolerated by Chinese outpatients with psoriasis,” Yan and colleagues wrote. “Methotrexate appeared to be more effective and had fewer adverse effects in patients without psoriatic arthritis compared with those with psoriatic arthritis. Although multicenter trials with larger sample size are needed to confirm these results, our findings suggest that methotrexate can be recommended as first-line treatment for psoriasis without arthritis.” – by Jason Laday

Disclosure: Yan reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Paul Schulman

    Paul Schulman

    The proliferation of new and updated guidelines on the treatment of psoriasis and PsA has prompted the re-examination of an old drug, methotrexate, for its true efficacy and proper placement in each condition’s treatment algorithms. In use for approximately 50 years, it has enjoyed recommendation more eminence-based than quality evidence-based, and thus in this paper, Yan and colleagues have performed a prospective 12-week study of methotrexate safety and efficacy among patients with psoriasis alone vs. those with both skin and joint components.

    The researchers discovered more similarities than differences between psoriasis groups with and without inflammatory arthritis: baseline Body Surface area (BSA), PASI 50 and 75, patients with hypertension, and cigarette and alcohol abstention or limitation did not differ. PASI 90 was greater in those with psoriasis only, this representing the sole efficacy parameter significantly differing from the group of psoriasis patients with PsA as well.

    In the realm of general and liver toxicities, dizziness and gastrointestinal symptoms were greater in psoriasis without PsA. Lab indicators in patients with PsA showed ALT levels > 2x normal; significantly higher than in psoriasis without inflammatory arthritis. Hematologic abnormalities were similar whether a psoriasis patient had arthritis or not. The addition of folic acid supplementation might have mitigated some of these toxicities. Methotrexate utilized for brief duration and low dose, only via oral administration, were also shortcomings in this endeavor. 

    Nonetheless, this study demonstrates that methotrexate is effective in cutaneous psoriasis described as moderate to severe, and perhaps better tolerated than in patients with the additional complication of PsA. Additional expanded data are needed to cement methotrexate as potential first line or early usage intervention in psoriasis vulgaris and psoriatic arthritis treatment recommendations.

    Furthermore, this study advances an additional intriguing perspective: Is there a phenotypic difference in response to this drug between psoriasis patients without arthritis and those with PsA? One suspects, however, that with similar genetic underpinnings and almost identical comorbidity profiles, expanded study of their response to a standard course of methotrexate therapy will reveal more similarities than differences. 

    • Paul Schulman, MD
    • Rheumatology Associates of Long Island
      Chief of the Division of Rheumatology
      St. Charles Hospital
      Member, Medical Policy Committee
      United Rheumatology

    Disclosures: Schulman reports no relevant financial disclosures.