2019 Brought Impressive Results for TNF Inhibitors, Research Into Monotherapy, Interest in CBD

This is an exciting time in rheumatology with impressive clinical trial results and promising outcomes for patients, explained Susan Manzi, MD, MPH, codirector of the Lupus Center of Excellence and chair of the Department of Medicine of West Penn Allegheny Health System, during a look back at the year during a session at the American College of Rheumatology annual meeting in Atlanta, Georgia.

Psoriatic Arthritis and Psoriasis

She started with psoriatic arthritis (PsA), which has had aggressive first-line tumor necrosis factor (TNF) treatments and impressive outcomes for interleukin (IL)-17 and IL-23 medications.

Research in Annals of Rheumatic Diseases found that golimumab, a TNF inhibitor, plus methotrexate was superior to methotrexate alone in treating PsA.¹ By the end of week 22, 81% of patients taking golimumab plus methotrexate had achieved Disease Activity Score remission compared with 42% of patients taking placebo plus methotrexate.

“You can see these separations as early as 8 weeks, which is pretty impressive,” Manzi said.

In addition to the improvements in remission, there was no difference in adverse events (AEs) or treatment-emergent AEs.

However, the IL-17 and IL-23 targets are the real highlight, Manzi said, adding that “these drugs have made a huge impact on the world of psoriasis and psoriatic arthritis.”

Risankizumab was successful in phase 2 trials in PsA, but it is also having an impact on psoriasis. In a trial published in The Lancet, risankizumab was superior to adalimumab in moderate to severe plaque psoriasis.² At 16 weeks, 72% of patients on risankizumab versus 47% on adalimumab achieved at least a 90% reduction in the Psoriasis Area and Severity Index (PASI 90). In addition, patients taking risankizumab were far more likely than patients taking adalimumab (84% vs 60%) to be almost clear of diseases based on the static Physician’s Global Assessment score at week 16.

“But what’s interesting is in those that had only an intermediate response to adalimumab and were rerandomized to either stay on adalimumab or go to risankizumab, you see even more impressive results,” Manzi said.

When looking at the PASI 90 and Physician’s Global Assessment, patients who were rerandomized had “an impressive improvement in what we would consider fairly refractor to adalimumab psoriasis patients.”

In addition, there were no safety concerns with risankizumab and the quality of life was superior to adalimumab, she explained. As a result, she recommended everyone stay tuned to phase 3 trials for PsA.

“We keep raising the bar of what we’re seeing in terms of the primary outcomes” for PsA, Manzi said. “PASI 75 was always the target before…it’s now the PASI 90 and 100.”

JAK Inhibitors

In rheumatoid arthritis (RA) there have been some changing paradigms in clinical trials. The Janus kinase (JAK) inhibitors have been in the spotlight, more so looking at refractory patients who have failed previously on biologic disease-modifying antirheumatic drugs (bDMARDs). Another area being explored in RA is the idea of monotherapy where background therapy can actually be discontinued.

Research on the FINCH 2 phase 3 trials published in JAMA found that, compared with placebo, more patients with moderate to severe RA on filgotinib who had tried at least 3 previous bDMARDs achieved a clinical response in 12 weeks.³

In addition, there was a rapid onset, which is pretty typical of JAK inhibitors, Manzi said, and responses were maintained or improved over 24 weeks.

As these agents become more effective, the idea of monotherapy is being raised, she noted, referencing a paper in The Lancet that looked at upadacitinib.⁴ The study found that upadacitinib, another JAK inhibitor, used as a monotherapy in active RA in patients who had an inadequate response to methotrexate had more patients who achieved a 20% improvement in the American College of Rheumatology criteria (ACR 20). By week 14, 68% of patients on upadacitinib 15 mg and 71% of patients taking upadacitinib 30 mg achieved ACR 20 compared with just 41% of patients who continued with methotrexate.

Biosimilars in Rheumatology

Manzi also touched on biosimilars, which she said continue to “march on.” There are biosimilars now for adalimumab, etanercept, infliximab, and rituximab, but there is clearly greater use in Europe than in the United States. However, there are a lot more biosimilars in the pipeline.

“Although there appears to be similar efficacy and safety and immunogenicity with the biosimilars, there is some interesting things we have to contend with as rheumatologists,” Manzi said.

Sometimes when switching patients, there is a nocebo effect, which results in increased disease activity. This effect occurs when patients know they are switching from the reference to the biosimilar and there may be the thought of inefficacy based on perceptions, Manzi explained.

In general, though, there is evidence, mostly in Europe, that access to treatments increases with biosimilars and costs go down, she said.

Impact of Cancer Cures

Manzi also took some time to go over immune checkpoint inhibitors, which are used in cancer, because the adverse effects trickle over into rheumatology. These treatments are curing cancer, and Manzi has started to see patients who had stage IV breast cancer who no longer have any detectable disease, but now have autoimmune manifestations.

At the annual meeting there were 61 different abstracts that look at the different autoimmune conditions that rheumatologists might see in patients who were treated with programmed cell death 1, programmed death-ligand protein 1, or cytotoxic T-lymphocyte-associated protein 4 inhibitors.

“But these drugs are not going anywhere, because they are literally curing cancer,” Manzi said.

Medical Cannabis

Finally, one area that Manzi suggested everyone keep an eye on medical cannabis for future meetings. “We cannot avoid it, it is here,” she said.

A survey on social media showed that more than 60% of respondents reported some use of cannabidiol (CBD) treatment for a medical condition. The respondents were 51% female, 40% between the ages of 55 and 74 years old, and 70% were college graduates.

They used CBD for chronic pain, arthritis, and anxiety, for the most part, but there were responses for fibromyalgia and autoimmune disease.

Manzi noted that there is little data currently on the use of medical cannabis with the exception of epilepsy, which has an approved treatment with CBD. However, there are 83 ongoing clinical trials with CBD in the United States.

“So, the bottom line is: It’s here, they’re ordering if off of Amazon, and we as a community are going to have to have a better understanding of the impact of medical cannabis on our conditions,” Manzi said.

References

1. van Mens LJJ, de Jong HM1, Fluri I, et al. Achieving remission in psoriatic arthritis by early initiation of TNF inhibition: a double-blind, randomised, placebo-controlled trial of golimumab plus methotrexate versus placebo plus methotrexate. Ann Rheum Dis. 2019;78(5):610-616. doi: 10.1136/annrheumdis-2018-214746.

2. Reich K, Gooderham M, Thaçi D, et al. Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial. Lancet. 2019;394(10198):576-586. doi: 10.1016/S0140-6736(19)30952-3.

3. Genovese MC, Kalunian K, Gottenberg JE, et al. Effect of filgotinib vs placebo on clinical response in patients with moderate to severe rheumatoid arthritis refractory to disease-modifying antirheumatic drug therapy: the FINCH 2 randomized clinical trial. JAMA. 2019;322(4):315-325. doi: 10.1001/jama.2019.9055.

4. Smolen JS, Pangan AL, Emery P, et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet. 2019;393(10188):2303-2311. doi: 10.1016/S0140-6736(19)30419-2.