The SAPHYR study represents a 'major turning point for the treatment of PMR', says Australian expert.
Patients with polymyalgia rheumatica taking interleukin-6 inhibitor sarilumab had a higher rate of remission and lower glucocorticoid exposure compared with those taking placebo, a phase 3 study has found.
The multicentre international SAPHYR trial set out to evaluate the efficacy and safety of sarilumab in patients with polymyalgia rheumatica who had a disease flare while they were tapering glucocorticoid therapy.
“The SAPHYR study published today in the NEJM represents a major turning point for the treatment of PMR,” said Melbourne rheumatologist Dr Claire Owen.
“Sarilumab has already been approved by the FDA in the US as the first biologic medication for relapsing disease. However, this is our first look at the full results, and they really are quite exciting,” said Dr Owen, who has a special interest in polymyalgia rheumatica.
A total of 118 patients were randomised 1:1 to receive 52 weeks of fortnightly 200mg sarilumab plus a 14-week prednisone taper or fortnightly placebo plus a 52-week prednisone taper. Patients who flared in the first 12 weeks could take rescue prednisone.
The primary outcome was sustained clinical remission, defined as achievement of disease remission by week 12, absence of flare from week 12 to 52, sustained reduction in CRP from week 12 to 52, and no rescue therapy from week 12 to 52.
Around 28% of the sarilumab group achieved sustained remission, compared with around 10% of controls, a statistically significant result (p=0.02).
“On first look, this doesn’t seem all that significant, but it is worth noting that the primary outcome measure in this trial set a very high bar, and patients in the sarilumab group were off prednisolone completely by week 14 whereas the placebo group received a 52-week taper,” Dr Owen told Rheumatology Republic.
Sarilumab also demonstrated a steroid-sparing effect, with the median cumulative glucocorticoid dose at 52 weeks significantly lower in the sarilumab group than in the placebo group (777mg vs 2044mg; P<0.001).
“Not surprisingly, the treatment group achieved a much lower median cumulative glucocorticoid dose, but there was also less requirement for rescue therapy to treat disease relapse,” said Dr Owen.
“This is pertinent given the patient population in this study comprised those with a median disease duration of 300 days who were taking a median prednisolone dose of 10mg/day at baseline.”
Dr Owen pointed out that no major safety concerns were raised, with neutropoenia being the commonest adverse event in the sarilumab group (like that seen with the IL-6 blocker tocilizumab). Arthralgia, diarrhoea and hypertension also reported by more than 10% of participants.
Results for patient-reported outcome measures, including quality of life, favoured sarilumab.
“All in all, this is a very positive development for patients living with relapsing PMR, who until now have been forced to walk the line between disease control and progressive accumulation of glucocorticoid-related adverse events,” said Dr Owen.
“Hopefully, it is the first of many new therapeutic options in this space.”
The trial was sponsored by Sanofi and Regeneron Pharmaceuticals.
