In Peripheral Spondyloarthritis, Early Biologic Needed

Ingrid Hein

October 11, 2018

GHENT, Belgium — For patients with peripheral spondyloarthritis who have achieved remission and are tapering their biologic — in this case, golimumab — the addition of concomitant methotrexate does not increase biologic-free remission rates, an extension of the CRESPA trial shows.

Patients cannot sustain remission with conventional disease-modifying antirheumatic drugs alone, said Philippe Carron, MD, PhD, from Ghent University Hospital in Belgium. Biologics are needed for remission to return.

"This underscores the overall weak efficacy of methotrexate in peripheral spondyloarthritis," he said here at the International Congress on Spondyloarthritides 2018.

Results from the CRESPA (NCT01426815) trial showed that more than half the 60 patients who started the TNF-alpha inhibitor golimumab when symptom duration was less than 12 weeks achieved remission, as reported by Medscape Medical News.

CRESPA Extension

Follow-up has continued out to 2.4 to 5.8 years. Of the 49 patients who achieved remission, 26 (53%) remain in biologic-free remission. The remaining 23 (47%) patients relapsed at a median 32 weeks.

"If you intervene with aggressive TNF-alpha inhibitor treatment at the very beginning of symptoms, you can stop the disease in half of patients," said Carron.

"We think the innate immune system plays a role; you can change the autoimmunity at this early stage," he explained. "Early intervention offers a chance to get patients into remission and drug free."

However, that autoimmunity reversibility decreases over time in patients peripheral spondyloarthritis. As the disease progresses, there seems to be an interplay between the innate and the adaptive immune systems, said Carron. After that, it's "too late to reverse the disease."

Treatment with biologics has been shown to maintain remission in patients, he said. "But you will not be able to stop the disease; patients relapse eventually."

In the CRESPA extension trial, 31 patients from the original study who did not achieve remission or who experienced a recurrence of symptoms within 1 year continued on open-label golimumab 50 mg monthly.

To date, 25 patients have completed the extension and 21 were in remission at week 104.

To test the theory that patients would be more likely to attain remission during the tapering of biologic treatment, those 21 patients continued on 12 weeks of golimumab plus methotrexate 15 mg weekly.

But "after 3 to 6 months, most of them relapsed again," Carron reported.

Biologic-Free Remission

Currently, five of the 21 (24%) patients have maintained biologic-free remission with methotrexate monotherapy. Disease activity recurred in 14 patients at a mean of 28.6 weeks, and two patients experienced adverse events related to methotrexate.

The patients who experienced relapse developed of arthritis, with a median of four tender and three tender swollen joints. In addition, seven of the 14 patients developed dactylitis and nine developed mild cases of psoriasis.

"It looks like methotrexate cannot help at this stage," he said.

The relapsed patients restarted golimumab, which restored remission within 12 weeks. "The biologics are expensive but they work very well," Carron said.

There is a window of opportunity but we don't know what it is yet.

"This trial is important because we have the belief that this disease is chronic. But when we intervene early we can see sustained clinical remission," he added. "There is a window of opportunity but we don't know what it is yet."

"We have to continue looking for biomarkers," said Helena Marzo-Ortega, MD, from the Leeds Biomedical Research Centre, University of Leeds, in the United Kingdom.

The majority of these patients had psoriasis, she pointed out. "That is a factor for prognosis of prediction of disease continuation. We need to study different subsets of patients to further research this."

"We really need to recognize the disease in the early stages," Carron added. Structural damage can only be prevented with aggressive biologic treatment, but only in early disease.

Carron has disclosed no relevant financial relationships. Marzo-Ortega has received honoraria from AbbVie, Celgene, Janssen, Lilly, Novartis, Pfizer, and UCB.

International Congress on Spondyloarthritides (SPA) 2018. Presented October 5, 2018.

Follow Medscape Rheumatology on Twitter @MedscapeRheum and Ingrid Hein @ingridhein

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