Sarilumab shows potential for relapsing polymyalgia rheumatica

The monoclonal antibody sarilumab demonstrated significant efficacy in individuals with relapsing polymyalgia rheumatica (PMR), findings from the phase III SAPHYR trial have shown.

“The primary endpoint of sustained remission at week 52 was achieved, [as was the] secondary endpoint of cumulative glucocorticoid (GC) dose, with clinical and statistical significance,” said Dr Bhaskar Dasgupta from the Anglia Ruskin University Cambridge Campus, East Anglia, UK, at EULAR 2022.

At week 52, more sarilumab vs placebo recipients achieved sustained remission (28 percent vs 10 percent; p=0.0193). This significant effect was similarly seen in a sensitivity analysis excluding C-reactive protein (CRP) from the sustained remission definition (32 percent vs 14 percent; p=0.028). [EULAR 2022, abstract LB0006]

When stratifying by components of sustained remission, all were better with sarilumab vs placebo: achievement of remission by week 12 (47 percent vs 38 percent), as well as absence of flare (55 percent vs 33 percent), sustained CRP normalization (67 percent vs 45 percent), and successful adherence to prednisone taper from weeks 12 to 52 (50 percent vs 24 percent).

Other secondary endpoints

The likelihood of having a flare after achieving clinical remission was almost halved with sarilumab vs placebo (hazard ratio, 0.56; p=0.0153).

Median actual cumulative GC dose was higher with placebo vs sarilumab (2,044 vs 777 mg), as the placebo arm required 52 weeks of therapy as opposed to 14 weeks in the sarilumab arm, explained Dasgupta. Looking at the actual and expected cumulative GC doses, a 200-mg difference was seen between arms (p=0.0189). “This is related to the higher incidence of flares in the placebo arm, which required treatment with GCs,” he continued.

Mean cumulative GTI* scores numerically favoured sarilumab over placebo (51.7 vs 57.9 [cumulative worsening score] and –1.1 vs –0.5 [aggregate improvement score]).

Treatment-emergent adverse event (TEAE) rate was higher with sarilumab vs placebo (95 percent vs 84 percent), mainly due to the incidence of neutropenia (15 percent vs 0 percent), which is a well-known side effect of interleukin-6 (IL-6) inhibition. There were no unexpected serious TEAEs outside the safety profile of sarilumab, noted Dasgupta.

Major treatment effects in patient-reported outcomes (PROs) were also seen, particularly in the SF-36** Physical (least squares mean [LSM], 4.78; p=0.0172) and Mental Component Scores (LSM, 4.75; p=0.0295), FACIT-Fatigue** (LSM, 3.74; p=0.0567), EQ-5D** – Single Index Utility (LSM, 0.13; p=0.0336), changes from baseline in HAQ-DI** (LSM, –0.246; p=0.0543) and MD-VAS** (LSM, –10.097; p=0.0411), and PMR-AS** (LSM, –5.30; p=0.0002).

“We were very excited to concentrate on PROs, because [these] are actually lower at onset than what we see with rheumatoid arthritis (RA),” noted Dasgupta. “These improvements may directly relate to the inhibition of IL-6 … [which] plays a key role in PMR.”

Targeting IL-6 signalling

SAPHYR evaluated 118 individuals (median age 70 years, 69 percent female) with steroid-resistant active PMR who flared on prednisone ≥7.5 mg/day. Participants were randomized 1:1 to receive sarilumab 200 mg Q2W + 14-week GC taper or placebo + 52-week GC taper. Most patients had received prior immunosuppressants***, the most common being methotrexate (8 percent and 17 percent in the respective sarilumab and placebo arms). Median PMR duration was shorter in the sarilumab vs the placebo arm (292 vs 310 days).

Sarilumab, which has been approved for the treatment of moderate-to-severe RA that does not respond well to DMARDs^#, targets IL-6 receptors and inhibits IL-6 signalling. IL-6 receptor inhibition leads to increased remission rates and reductions in disease symptoms, inflammation, and cumulative steroid dose. [Ann Rheum Dis 2022;81:838-844]

“[Taken together,] steroid-refractory PMR patients receiving sarilumab had sustained remission, less PMR flares, reduced risk of PMR flares, and greater and clinically relevant improvements in quality of life,” said Dasgupta. “Safety was consistent with the known profile of sarilumab.”