The current treatment paradigm for psoriatic arthritis (PsA) differs greatly from that before the launch of the first anti-TNF (tumor necrosis factor) antibody more than a decade ago. Now, with five differently designed TNF inhibitors/antibodies, two antibodies targeting other cytokine pathways—namely IL-12/23 and IL-17—plus a synthetic chemical targeting PDE-4 (phosphodiesterase-4) on the market, rheumatologists, drug makers, payers, and investors all turn to the ACR annual meeting where new data for Phase III drugs and long-term studies of already approved drugs are announced.

This year’s ACR annual meeting took place in Washington, D.C., from Nov 11 to 16 and attracted over 16,000 attendees from around the world.

An important topic in PsA discussed throughout the five-day meeting is what approach best benefits PsA patients. Over the past two decades, the concept of PsA has changed from a slow-progressing disease to a heterogeneous, progressive, severe disease. Nearly half of PsA patients develop erosive disease within the first two years, noted Dafna D. Gladman, MD FRCPC, from the University of Toronto.1 Although PsA affects fewer patients than rheumatoid arthritis (RA), it is harder to make a diagnosis, often leading to delayed treatment, which can have severe consequences. “Even a 6-month delay in consultation leads to untoward outcomes,” Dr. Gladman said in a lecture session on PsA at the ACR meeting. Primary research by Decision Resources Group finds that only 54% of PsA patients in the seven major markets are drug-treated.2 Furthermore, the lead author of the TICOPA (TIght Control of Psoriatic Arthritis) study, Laura C. Coates, PhD MBChB, from the University of Leeds, presented data to support that a high treatment objective and faster therapy escalation lead to convincingly better outcomes in early PsA patients.3 With a heightened focus on early and aggressive treatment in PsA, it will be interesting to watch how physicians respond to these data and which drug(s) will be favored by this ongoing trend.

The most exciting part of the conference regarding PsA was the data release for tofacitinib (Pfizer’s Xeljanz), an oral JAK inhibitor.4, 5 Two dosages of tofacitinib, 5 mg and 10 mg b.i.d., met their primary end points in both TNFi-naive and –experienced PsA patients in two separate Phase III placebo-controlled studies. In the TNFi-naive study, the current market leader adalimumab was used as an active comparator group and was shown to achieve comparable outcomes as the two doses of tofacitinib in all musculoskeletal, skin clearance, and quality of life outcomes at week 12. Although the study was not powered to detect differences between therapy arms, these data will be welcomed by regulators and payers and also give peace of mind to prescribing physicians.

It is encouraging to see that even the lower dose of tofacitinib proved to be effective in PsA patients who had an inadequate response to TNFi in the second study, as patients become harder to treat after prior treatment failure. The safety profile of the two drug arms did not show any unexpected side effects beyond the drug’s known risk for zoster infection. In the TNFi-naive study, there were one and three malignancy cases reported in the 10 mg (N=104) and 5 mg (N=107) tofacitinib arms, respectively, while none in the adalimumab group (N=106). Prescribers have reason to be cautious, but it is unlikely a causative link between tofacitinib and malignancy will be established due to a lack of dose-dependent effect and no malignancy incidence reported in the TNF-experienced study. Bear in mind that U.S. rheumatologists have years of experience in using this drug at 5 mg b.i.d. in RA and they are comfortable dealing with any of its side effects. These results indicate that rheumatologists should be prepared to prescribe 5 mg tofacitinib in their PsA patients as well, pending regulatory filing and approval. Interestingly, the drug demonstrated a dose-dependent response in psoriatic plaque clearance, which raises the possibility that Pfizer may also file with the higher dose, even though both doses were rejected by the FDA for treating psoriasis. However, even if the higher dose was rejected by the FDA, tofacitinib would stand to receive a competitive reimbursement status because of its well-rounded clinical profile. A successful approval in PsA by the FDA will no doubt propel its prospect in Europe, where physicians are awaiting approval of the drug in RA and, eventually, PsA patients.

The positive Phase II data release of the first IL-23 inhibitor, guselkumab (Janssen) was another highlight of the conference regarding PsA.6 Abstracts on Phase IV studies and registry studies of approved PsA therapies continued to draw crowds of attendees, as lingering questions remain in the field: whether to use secukinumab in patients with inflammatory bowel diseases, what the long-term efficacy and safety profiles of apremilast look like, and whether ustekinumab is better than the TNF inhibitors in managing cardiovascular comorbidities. By the time the conference concluded, I had already jotted down many questions I want to include in DRG’s next physician surveys. Some of the questions were the brainchild of my conversations with key opinion leaders, and some of them came from unplanned chats with medical liaisons and clinical researchers about the increasingly crowded PsA market that eagerly awaits the next breakthrough. Whether a breakthrough comes from an oral drug that is as effective as injectable biologics or a new biologic with a novel mechanism of action, we can only look into the market to find out the answer!

Despite the clinical successes that have been claimed by the newly approved PsA drugs, there are still many challenges ahead. Rheumatologists today still see patients with very severe forms of PsA that have progressed so badly that none of the current drugs seem to work. Secondly, rheumatologists rely mostly on dermatologists’ referrals to identify patients with PsA. This process could be more effective and needs extra efforts in integrating instruments to identify patients with early PsA during appointments with a dermatologist. The research on biomarkers for early PsA showed some interesting preliminary findings at ACR this year and will likely be a hot topic at the conference next year. Lastly, as the future of medicine becomes more personalized, studies of PsA therapies need to provide more information on their effects on patients’ comorbidities—more than half of PsA patients have one or more comorbidities. To those who are also interested in these topics, I will see you at the 2017 ACR meeting in San Diego!

 

References

[1] Kane D, et al. A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatology, 2003; 42:1460-8

[2] Yang H. Disease Landscape & Forecast®: Psoriatic Arthritis (G7) 2016

[3] Coates L, et al. What should be the primary target of ‘Treat to Target’ in PsA? American College of Rheumatology Annual Conference; 2016; Washington, D.C., abstract #3095

[4] Mease PJ, et al. Efficacy and safety of tofacitinib, an oral Janus Kinase inhibitor, or adalimumab in patients with active psoriatic arthritis and an inadequate response to conventional synthetic DMARDs: A randomized, placebo-controlled, Phase 3 trial. American College of Rheumatology Annual Conference; 2016; Washington, D.C., abstract #2983

[5] Gladman DD, et al. Efficacy and safety of tofacitinib, an oral Janus Kinase inhibitor, in patients with active psoriatic arthritis and an inadequate response to tumor necrosis factor inhibitors: OPAL Beyond, a randomized, double blind, placebo-controlled, Phase 3 trial. American College of Rheumatology Annual Conference; 2016; Washington, D.C., abstract #10L

[6] Deodhar AA, et al. Efficacy and safety results of guselkumab, an anti-IL23 monoclonal antibody, in patients with active psoriatic arthritis over 24 weeks: a Phase 2a, randomized, double-blind, placebo-controlled study. American College of Rheumatology Annual Conference; 2016; Washington, D.C., abstract #4L

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