Rheum in Review: SCOTUS on Fosamax, FDA Drug Approval, Secukinumab Safety, and More

By Kaitlyn D’Onofrio

Here are the top stories covered by DocWire News this week in the Rheumatology section. In this edition, read about the Supreme Court’s stance on hundreds of lawsuits against pharmaceutical giant Merck, the latest Food and Drug Administration (FDA) approval for a plaque psoriasis treatment for adolescent patients, the long-term safety of secukinumab, and how opioids may affect outcomes in joint arthroplasty patients.

Pharmaceutical giant Merck potentially faces several hundred lawsuits in relation to its osteoporosis drug, Fosamax. This week, the U.S. Supreme Court decided that it should be up to a judge—not a jury—to decide if these cases should move forward. The suits were brought against the company by patients who took Fosamax between 1999 and 2010 and sustained unusual femur fractures. Fosamax was granted Food and Drug Administration (FDA) approval in 1995, at which time an association was observed between the drug and thigh fracture, although it was not significant enough to warrant a warning label. Further studies eventually strengthened this connection, leading Merck in 2008 to apply for a warning to be added to both the adverse reactions and precautions sections of Fosamax’s label cautioning patients of “low-energy femoral shaft fracture.” The FDA agreed to include an adverse reactions update but said that to use the term “stress fractures,” which Merck suggested, was “inadequate,” adding that “[i]dentification of ‘stress fractures’ may not be clearly related to the atypical subtrochanteric fractures that have been reported in the literature.” Merck did not reapply to change the language, and in 2011—based on its own findings—the FDA added an “atypical femoral fractures” warning to Fosamax’s label.

The FDA has extended its approval of plaque psoriasis drug calcipotriene (Sorilux) to include adolescent patients aged 12 years and older. Sorilux is a 0.005% topical foam manufactured by Mayne Pharma. The FDA originally approved calcipotriene in 2010; its safety and efficacy were initially tested in two multi-center, randomized, double-blind, vehicle-controlled clinical studies evaluating 659 psoriasis patients. For eight weeks, patients randomly received twice daily doses of calcipotriene or vehicle. The 5-point Investigator Static Global Assessment scale (ISGA) was used to evaluate baseline disease severity: (grade 0: clear, no evidence of scaling, erythema, or plaque thickness; grade 1: almost clear, occasional fine scale, faint erythema, and barely perceptible plaque thickness; grade 2: mild, fine scale with light coloration and mild plaque elevation; grade 3: moderate, coarse scale with moderate red coloration and moderate plaque thickness; grade 4: severe, thick tenacious scale with deep coloration and severe plaque thickness). Treatment success—defined as a grade 0 or 1 and a two-grade improvement from baseline—was achieved in 14% of calcipotriene patients and 7% of vehicle patients in the first study; in the second study, 27% and 16% of patients, respectively, achieved treatment success.

A recent study evaluated the long-term safety and efficacy of secukinumab (Cosentyx), a human immunoglobulin G1-kappa monoclonal antibody that inhibits interleukin-17A, in moderate-to-severe plaque psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Researchers evaluated 21 randomized controlled trials assessing secukinumab (300 mg, 150 mg, or 75 mg) use in PsO (14 phase 3 trials, one phase 4 trial), PsA (three phase 3 trials), and AS (three phase 3 trials). In total, data for 5,181 PsO patients, 1,380 PsA patients, and 794 AS patients were evaluated. Exposure-adjusted incident rates for any serious AE with secukinumab treatment were 6.9, 7.9, and 6.3 per 100 patient-years among PsO, PsA, and AS patients, respectively. The most common adverse event (AE) was upper respiratory infection. Discontinuation rates due to AEs were similar across the three groups: 331 (6.4%) for PsO patients, 104 (7.5%) for PsA patients, and 58 (7.3%) for AS patients.

Patients undergoing total joint arthroplasty (TJA) could have worse outcomes if they are preoperative opioid users—notably, they may experience increased pain and higher postoperative opioid use. Data were gathered from Ovid, Embase, Cochrane Library, Scopus, Web of Science Core Collection, and CINAHL on preoperative and postoperative patient-reported outcomes (PROs) in patients with and without a history of opioid use undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). Six cohort studies with data on 7,356 TJA patients were included in the final analysis—three studies had data on TKA patients, while two studies evaluated both TKA and THA patients, and one study only reviewed THA data. Overall, the study authors concluded that TJA patients appear to have worse pain and functional outcomes if they are preoperative opioid users compared to opioid-naïve patients; those with a history of opioid use also tend to use more opioids after surgery. Still, the authors noted that both sets of patients benefited from TJA. They also added that further research is necessary to determine “our understanding of the independent impact of opioid use on outcomes after surgery.”