‘On the cusp of a new era’: Promising drugs may tackle unmet needs in giant cell arteritis

Nearly all rheumatologists who responded to a recent survey reported patients with giant cell arteritis are in dire need of new treatments, according to a market analysis from Spherix Global Insights.

The analysis, conducted between Feb. 15 and March 1 among 109 rheumatologists, indicates that 98% of respondents stated there is a “moderate to extremely high” unmet need for new treatments for GCA.

“I agree that there is a high unmet need for new treatments, as the only currently FDA approved medication is tocilizumab,” Jason Springer, MD, MS, co-director of the Vanderbilt Vasculitis Center, told Healio. “Although tocilizumab has been effective for a large number of patients, there is still a large proportion of patients who have contraindications with, do not tolerate, or flare with tocilizumab.”

According to Springer, who was not involved with the Spherix analysis, most rheumatologists are not satisfied with the current treatment options.

“When compared to other diseases such as rheumatoid arthritis and ANCA-associated vasculitis, there is a paucity of phase 3 randomized, controlled trial data available from which to choose therapeutic options,” he said. “That being said, I think there are many promising treatment options on the horizon.”

‘Degree of hesitance’

Some of the promising treatment options for GCA currently include secukinumab (Cosentyx, Novartis), guselkumab (Tremfya, Johnson & Johnson) and upadacitinib (Rinvoq, AbbVie).

“Based on what we know about the pathogenesis of GCA, all of these therapies could hold potential,” Springer said. “However, I say that with a degree of hesitance as there are multiple examples of prior promising therapeutics that have failed in phase 3 trials, including methotrexate and TNF inhibitors.”

Looking deeper into the pipeline, Springer suggested that mavrilimumab (Kiniksa) and abatacept (Orencia, Bristol Myers Squibb) additionally offer an encouraging safety and efficacy profile.

“Also, I think JAK inhibitors in general hold promise,” he said.

‘Historically been ignored’

According to the Spherix analysis, steroid sparing is among the most important reasons researchers continue to push for newer agents in the GCA space.

Further data from the analysis — which included a cohort of 101 rheumatologists who completed a 35-minute online survey, while an additional eight participants responded via a tele-web interview — showed that rheumatologists believe interleukin (IL)-6 inhibition with tocilizumab (Actemra, Genentech) is a viable option for reducing glucocorticoid and methotrexate use.

“Prior to the approval of tocilizumab for GCA, the standard of care was to treat with long, slow glucocorticoid tapers,” Springer said. “This treatment strategy is associated with frequent relapses and glucocorticoid-related side effects in a population that is especially vulnerable, including the elderly. It is now recognized that we should be minimizing the glucocorticoid burden as much as possible, not only in GCA but other forms of vasculitis and autoimmune diseases.”

It is for this reason that Springer described the studies leading to the FDA approval of tocilizumab as a “major milestone” in the therapeutics of GCA.

“The research in and approval of tocilizumab stimulated a degree of excitement by pharmaceutical companies in a disease that has historically been ignored,” he said. “I believe we are on the cusp of a new era in the treatment of GCA. As mentioned above, tocilizumab does not work for all patients so there is need for more treatment options.”

‘We can do better’

Although most clinicians understand the need to minimize glucocorticoid use, minimizing methotrexate use is a different story.

“Methotrexate has been evaluated in multiple studies with varying results,” Springer said. “Some studies show no benefit with methotrexate, while others show a moderate steroid sparing benefit. The studies that seemed to show a benefit — in terms of minimization of glucocorticoids and relapses — tended to use higher doses of methotrexate over a longer period of time. Although methotrexate may be an acceptable treatment option in some patients, we can do better.”

However, doing better will entail significantly more research, according to Springer.

“We focus here on treatment options of GCA,” he said. “Although it is important to find new treatment options, there is also a large unmet need to find better diagnostic tests and biomarkers of disease activity.”

Temporal artery biopsy and/or ultrasound have been used to diagnose cranial GCA, but despite a large patient population, this diagnosis “never” appears on these diagnostic modalities, according to Springer.

“In addition, tocilizumab makes our traditional biomarkers of disease activity, including CRP and erythrocyte sedimentation rate, less reliable,” he said. “I would like to see a push toward diagnostic and biomarker development in GCA.”

References:

Market Dynamix: Giant Cell Arteritis (US) 2024. https://www.spherixglobalinsights.com/rheumatology. Published March 27, 2023.

For more information:

Jason Springer, MD, can be reached at 3601 The Vanderbilt Clinic, Nashville, TN 37232; email: jason.springer@vumc.org; jakullman@vasculitisfoundation.org.