Adempas Beneficial in Scleroderma, Other PAH Patients with Connective Tissue Disease

Scleroderma patients with pulmonary arterial hypertension (PAH) benefit equally well from treatment with Adempas (riociguat) as PAH patients with other types of connective tissue disease (PAH-CTD), according to research from the University of Paris-Saclay in France.

The study, “Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2,” published in the journal Annals of the Rheumatic Disease, also showed that the entire group of connective tissue disease patients had a similar survival rate as other PAH patients, which further supports Adempas for scleroderma and other connective tissue conditions that lead to PAH.

During the development of Adempas, researchers found in addition to its ability to relax blood vessels, that the drug has anti-fibrotic effects, anti-inflammatory impact, and prevents blood vessel remodeling.

Two Phase 3 clinical trials, PATENT-1 (NCT00810693) and the follow-up long-term PATENT-2 study (NCT00863681), investigated how Adempas impacts PAH in patients, but initial analyses from the studies only looked at the whole patient group — a mix of patients with and without connective tissue disease.

A study funded by Adempas developer Bayer Pharma, researchers took a closer look at scleroderma patients and those with other connective tissue diseases.

The PATENT-1 trial enrolled 443 patients, of which 111 had connective tissue disease. Researchers divided connective tissue conditions into either scleroderma (66 patients), or other types in a mixed group of patients with systemic lupus erythematosus, rheumatoid arthritis or undefined disease. Of the original 111 patients, 94 continued to the PATENT-2 trial where scleroderma patients were treated for an average of 29 months.

At the end of the 12-week study, connective tissue disease patients who received a 2.5 mg dose Adempas improved in the 6-minute walking distance (6MWD) test by an average of 59 feet.  Patients receiving placebo worsened during the same time.

Scleroderma patients had a much smaller improvement of only 13 feet, but because scleroderma patients who received placebo deteriorated more during the 12 weeks of the trial, the difference was larger with an average of 141 feet more in the Adempas group. The results were maintained two years later when explored in the PATENT-2 trial.

The first trial also showed that 97% of patients with some type of connective tissue disease either improved or stabilized after 12 weeks, defined as changes in the World Health Organization functional group assessement, with no differences between scleroderma and other patients. After two years, the numbers remained similar. Patients also improved some aspects of heart function and lung blood vessel resistance, although scleroderma patients improved less than other patients. The study did not find any evidence of Adempas affecting the blood pressure in the lungs.

Although the drug was generally effective, some patients experienced worsening disease during the long-term trial; 29% were hospitalized. Such events were more common in the scleroderma group, where 33% experienced worsening, compared to only 24% among other connective tissue disease patients. Survival rates did not differ between patients with or without connective tissue disease.

Patients with different type of underlying disease experienced adverse effects at the same rates. The only exceptions were patients treated with immunosuppressants during the trials who experienced adverse effects more often.

Researchers concluded: “Riociguat was well tolerated and associated with positive trends in 6MWD and other endpoints that were sustained at 2 years in patients with PAH-CTD.”