Tofacitinib leads to lasting improvements in dermatologic symptoms in OPAL Broaden and OPAL Beyond trials

Oral tofacitinib is a viable treatment option for patients with active psoriatic arthritis (PsA) who have had an inadequate response to other treatment options, such as disease modifying antirheumatic drugs (DMARDs) and tumor necrosis factor inhibitors (TNFi), according to results from a recent analysis published in the Journal of the European Academy of Dermatology and Venereology.

“Psoriatic arthritis (PsA) is a chronic, systemic immune-mediated inflammatory musculoskeletal disease, and symptoms can include peripheral arthritis, enthesitis, dactylitis, spondylitis, and skin and nail psoriasis, all of which can impact health-related quality of life (HRQoL). PsA occurs in up to 30% of patients with psoriasis — cutaneous signs and symptoms often precede skeletal manifestations, with the onset of psoriasis commonly occurring around 10 years prior to arthritic symptoms,” wrote researchers led by Joseph F. Merola, MD, MMSc, of Brigham and Women’s Hospital, Harvard Medical School, Boston.

Tofacitinib is the first and only FDA-approved, once-daily oral Janus kinase (JAK) inhibitor, first approved in February 2016 for the treatment of rheumatoid arthritis. In December 2017, it was approved for the treatment of active psoriatic arthritis.

Merola and colleagues did an analysis of data from the OPAL Broaden and OPAL Beyond phase III, double-blind, placebo-controlled trials of tofacitinib for the treatment of PsA. All patients (N=816) had active PsA. Those enrolled in the OPAL Broaden trial (n=422) had an inadequate response to treatment with one or more csDMARDs and were naïve to treatment with TNFi, while those in OPAL Beyond (n=394) had an inadequate response to one or more courses of TNFi.

In all, 73.9% and 62.7% of patients in OPAL Broaden and OPAL Beyond, respectively, had ≥ 3% affected body surface area (BSA) and median Psoriasis Area and Severity Index (PASI) total scores of 6.5 and 7.9, respectively. Nail psoriasis affected 78.4% and 70.3% of patients, respectively, while 43.1% and 41.1% had mild disease severity, and 21.8% and 20.3% had moderate disease severity based on the Physician’s Global Assessment of Psoriasis (PGA-PsO).

In the 12-month OPAL Broaden trial, patients were randomized to treatment with tofacitinib (5 or 10 mg BID), adalimumab (40 mg subcutaneous injection Q2W), or placebo advancing to tofacitinib at month three (5 or 10 mg BID). For the 6-month OPAL Beyond trial, researchers randomized patients to treatment with tofacitinib (5 or 10 mg BID) or placebo advancing to tofacitinib at month three (5 or 10 g BID). All patients also received a stable dose of one csDMARD, such as methotrexate, leflunomide, or sulfasalazine.

By month three, the percentage of patients who achieved PASI90 had increased with tofacitinib, and was significantly greater compared with placebo at month one for the 5-mg dose of tofacitinib (OPAL Broaden (P ˂ 0.001), as well as for the 10-mg dose in the OPAL Beyond study (P ≤ 0.05). Researchers observed no differences at month one for adalimumab versus placebo.

In the OPAL Broaden trial, at month three, PASI90 response rates were greater for the 5- and 10-mg doses of tofacitinib and adalimumab compared with placebo (P ˂ 0.01, P ˂ 0.001, and P ≤ 0.05, respectively). In the OPAL Beyond study, PASI90 response rates at month three were also significantly greater in patients treated with 10-mg tofacitinib compared with placebo (P ≤ 0.05).

PASI90 response rates increased from month three through the end of each study in all active treatment groups. In the OPAL Broaden study, by month 12, PASI90 response rates in patients with baseline PASI > 0 to ≤ 10 were greatest in patients treated with 10-mg tofacitinib (10 mg BID; 61.0%), followed by those treated with 5-mg tofacitinib (55.6%) and adalimumab (35.7%). In patients with the same PASI scores in the OPAL Beyond study, PASI90 response rates were 45.2% in the 10-mg tofacitinib group and 27.1% in the 5-mg tofacitinib group at month six.

In both studies, significantly more patients treated with both doses of tofacitinib achieved PGA-PsO response at months one and three compared with placebo, and the same was true for patients treated with adalimumab (all P ≤ 0.05).

All patients receiving active treatment showed improvements in Nail Psoriasis Severity Index (NAPSI) compared with baseline; there were no statistically significant differences in NAPSI scores between tofacitinib, adalimumab, and placebo at month three in either study.

In patients treated with both doses of tofacitinib, greater changes in Dermatology Life Quality Index (DLQI) scores compared with baseline were seen at months one and three in both studies compared with placebo (P ≤ 0.05). In the OPAL Broaden study, the same was true for comparisons of adalimumab and placebo at month three (P ≤ 0.05). Improvements in DLQI total scores were maintained up to month 12 in the OPAL Broaden study and up to month six in OPAL Beyond.

At all time points, treatment with the 10-mg dose of tofacitinib effected greater improvements in DLQI scores from baseline compared with the 5-mg dose of tofacitinib and to adalimumab in the OPAL Broaden trial.

Both tofacitinib doses effected greater improvements in Itch Severity Item (ISI) at month one and month three in both studies (all P ˂ 0.001) and with adalimumab compared with placebo in the OPAL Broaden study (P ≤ 0.05). ISI response (improvement from baseline of 4 or more units) was seen in significantly more patients treated with either tofacitinib dose at month one and month three compared with placebo (all P ˂ 0.01).

Finally, greater improvements from baseline in Patient’s Global Joint and Skin Assessment-Visual Analog Scale-Psoriasis question were seen with both tofacitinib doses in both studies at months one and three (all P ˂ 0.001) and with adalimumab compared with placebo in the OPAL Broaden study (P ˂ 0.01).

Limitations of both studies include the limitation of comparisons of active treatments with placebo to the three-month placebo-controlled portions of the study, hierarchical testing, limitation of dermatologic endpoints included, and the post-hoc nature of some analyses. In addition, the OPAL Broaden trial was not powered for statistical comparisons between tofacitinib and adalimumab.

“[T]his analysis of dermatologic endpoints from OPAL Broaden and OPAL Beyond found that in patients with active PsA and [inadequate response] IR to [conventional synthetic] csDMARDs or TNFi, tofacitinib improved dermatologic signs and symptoms and dermatology-related quality of life versus placebo at month three. Improvements in PASI75 and PASI90 were observed regardless of baseline dermatologic disease severity. Importantly, clinically meaningful improvements in dermatologic endpoints were sustained to the end of each study. These data confirm that tofacitinib provides a treatment option for patients with active PsA including burdensome dermatologic symptoms,” concluded Merola and fellow researchers.

Commenting on these results, Rhajat Bhatt, MD, Community Rheumatologist, of PRIME Rheumatology PLLC, Richmond, TX, noted:

“This study is comparing [tofacitinib] to placebo and is sponsored by Pfizer, the company that makes that medication. It’s comparing it to placebo, rather than standard of care. Newer trials really want medications compared to the standard of care. So, for psoriasis, if we’re looking at oral medications, they should have had something comparing [it] to methotrexate. That’s a vastly cheaper drug and is a first-line agent anyway, used for psoriasis. Again, we do not have a comparison to a TNF inhibitor either.”

Nevertheless, the take-home message for clinicians from these results is this, according to Bhatt:

“There’s an oral option to current existing biologics. Some patients have limitations, for example, traveling, etc. They cannot take TNF inhibitors, so they can try this medication.”

  1. Tofacitinib improved dermatologic signs and symptoms of disease in patients with active psoriatic arthritis and inadequate responses to other treatment options, including disease modifying antirheumatic drugs and tumor necrosis factor-inhibiting agents.

  2. In patients with active psoriatic arthritis, orally administered tofacitinib also improved dermatology-related quality of life.

E.C. Meszaros, Contributing Writer, BreakingMED™

Pfizer funded this study.

Merola is a consultant and/or investigator for AbbVie, Aclaris, Almirall, Biogen, Celgene, Dermavant, Eli Lilly, EMD Sorono, GSK, Incyte, Janssen, Kyowa Kirin Co, Leo Pharma, Merck Research Laboratories, Novartis, Pfizer Inc, Samumed, Sanofi Regeneron, Sun Pharma, and UCB; and is a member of the Burrage Capital Management Boston Advisory Board.

Bhatt disclosed no relevant relationships.

Cat ID: 158

Topic ID: 90,158,730,10,105,192,158,68,919,925