New Data for Anti-TNF Injection Treatment for Dupuytren’s

A novel anti-TNF injection treatment for Dupuytren’s disease, developed at the University of Oxford in the UK, was the subject of a randomized, double-blind, placebo-controlled Phase 2b trial. Final efficacy data from the study has just been released. The study, “Anti-tumor necrosis factor therapy for early-stage Dupuytren's disease (RIDD): a phase 2b, randomised, double-blind, placebo-controlled trial,” was published April 29, 2022, in The Lancet Rheumatology.

The trial enrolled 140 patients from two sites in the UK. The research team randomized patients 1:1 to the treatment arm or placebo. Those in the treatment arm received four injections of 40mg adalimumab in 0.4ml at baseline, with 12- and 18-month follow-up.

The trial assessed nodule hardness at 12 months and nodule size, measured using an ultrasound scan at 12 and 18 months. According to the company, major findings of the study were:

• Nodule hardness was lower in the anti-TNF treatment arm compared to placebo (-4.6AU; 95% CI -7.1 to -2.2; p=<0.0002) at 12 months and decreased further at 18 months (-5.8AU; 95% CI -8.7 to -3.0; p=<0.0001), 9 months after the last injection.
• Nodule size (area), measured using ultrasound scan, was also lower in the anti-TNF treatment arm compared to placebo at 12 months (-8.4mm²; 95% CI -13.8 to -2.9; p=<0.0025), and decreased further at 18 months (-14.4mm²; 95% CI -19.9 to -9.0; p=<0.0001).
• There were no treatment-related serious adverse events in the trial.
• Patient compliance was high, with 84% returning for all 4 injections.
• Fewer patients in the treatment group underwent or were awaiting surgery compared to placebo at 18 months. However, the overall numbers were small and longer-term follow up would be required to confirm this.

“These results present the potential for an earlier treatment for patients with Dupuytren’s disease, which is easy to diagnose at an early stage,” said James Woody, M.D., CEO of the study sponsor, California based 180 Life Sciences. “Treatment with anti-TNF injections could bring long lasting respite and prevent the disease from advancing to the stage that surgery is needed to maintain hand function. This study demonstrates that anti-TNF injections into the hand could have a durable response following treatment, potentially delaying or preventing the eventual progression to finger contractions and disability.”

“We believe that these results herald a dramatic change in treatment options for Dupuytren’s disease,” said Professor Sir Marc Feldmann, founder and co-chairman of 180 Life Sciences. “These results show that anti-TNF injections into the hand can be effective in controlling the palmar nodule, potentially preventing or reducing disease progression and avoiding the need for much more invasive treatments.”

Professor Jagdeep Nanchahal, a clinician-scientist at the University of Oxford and Chairman of the Clinical Advisory Board at 180 Life Sciences, told OTW, “The nodules became softer and smaller following four injections, and continued to regress for nine months after the final injection, this tells us the beneficial effect continues for some time after the last injection.”

“The disease tends to run in families and the diagnosis can be made on clinical criteria at an early stage,” said 180 Life Sciences CEO Woody to OTW. “However, patients currently must wait until their fingers are bent to get treated, as there is currently no approved treatment for early-stage Dupuytren’s disease. All treatments for late-stage disease have limitations, and this therapy may provide benefit earlier before any disability is present.”

Finally, noted Dr. Woody: “Based on the innovative discoveries by Professor Nanchahal and colleagues, the pathway that drives the Dupuytren’s fibrosis was elucidated, and TNF identified as a therapeutic target identified. The trial of anti-TNF for early stage was clinically tested and was amazingly effective as seen in the Lancet Rheumatology publication. For 180 Life Sciences to have its very first clinical trial be a success, suggests the company has both the scientific and clinical talent to be successful in future clinical trials.”

Professor Nanchahal added, “The safety profile is well-known as it has been administered to approximately 5 million people worldwide for other conditions. There were no grade 3 or above serious adverse events in the trial and local injection site reactions were similar to placebo.”