Prescription drug spending has skyrocketed over the past few years, with many Americans struggling to access proper treatment. Lawmakers have attempted to address this issue, but it is likely that the trend of escalating drug spending will continue as costly specialty drugs dominate the market.

All of the drugs that had the highest sales in 2016 are for specialty conditions, including autoimmune disorders and hepatitis C virus (HCV); however, the emergence of biosimilars may threaten their revenue into the future, according to The Motley Fool.

1. Adalimumab (Humira)
In 2016, adalimumab grossed $16.08 billion in sales, which is a 14.7% increase in revenue for AbbVie, according to the article. The drug is approved to treat several autoimmune conditions, including rheumatoid arthritis, ulcerative colitis, and psoriasis.

Biosimilars for adalimumab, including Boehringer Ingelheim’s product that has been submitted for regulatory review, may result in lowered spending on the biologic in the coming years.

2. Ledipasvir/sofosbuvir (Harvoni)
When this drug hit the shelves, many patients with HCV and healthcare providers experienced sticker shock. The high cost of the curative drug and the prevalence of HCV have driven the $9.08 billion sales for the drug, according to the article.

However, 2016 saw a 34.5% decrease in 2015 sales. Gilead may continue to see a downturn in profit from this blockbuster drug, as more patients are cured of HCV and with the approval of newer, less costly treatments.

3. Etanercept (Enbrel)
This autoimmune disease drug treats rheumatoid arthritis, plaque psoriasis, and psoriatic arthritis. Amgen and Pfizer reported $8.87 billion in total sales for etanercept in 2016.

While overall sales increased by 2.7%, Pfizer saw a downturn in overseas revenue in 2016 due to increased competition from biosimilars, according to the article. As more biosimilars are approved, it is likely that Amgen will see lower revenue in the United States and Canada.

4. Rituximab (Rituxan)
Partners Roche and Biogen reported total revenue of $8.58 billion for rituximab in 2016, which is a 2.7% increase from 2015. The drug is approved to treat non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, and granulomatosis with polyangiitis.

The Motley Fool reports that several rituximab patents are set to expire, meaning that biosimilar competitors will likely flood the market and reduce the biologic drug’s revenue.

5. Infliximab (Remicade)
Johnson & Johnson and Merck report a 10.6% decrease in revenue from 2015, with infliximab generating nearly $7.83 billion in 2016.

This significant reduction in revenue is likely attributable to biosimilar competition in Europe and their emergence in the United States. Pfizer recently launched infliximab-abda (Renflexis) after its approval in April 2017, which is just 1 of the biosimilars approved. This competition will likely further affect the branded biologics.