- For International Humira, the debate centers on whether there is further downside to AbbVie’s 2019 guidance of a 30% ex FX decline. This follows several downward revisions by management over the last year.

- For US Humira, the drug will face competition from several novel mechanisms of action, including JAK, IL-17, and IL-23 inhibitors in rheumatoid arthritis and psoriasis. These drugs could also present downside risk to Humira estimates.

- Skyrizi and upadacitinib are the most often-cited drugs within the pipeline. While they could offset some of the gap, AbbVie is looking at a $10B+ revenue gap from Humira, and Skyrizi/upadacitinib do not look exciting enough to cover the shortfall.

- AbbVie's Humira represents a sizeable portion of revenue, and will see biosimilar competition soon in the EU and in the US

- In the EU, a more biosimilar-friendly environment (net of regional differences) and the launch of at least three biosimilars could lead to more significant declines than expected.

- In the US, competition is not expected until 2023, and biosimilars have not gained much traction to date. However, the environment is changing.

- The pipeline looks promising with numerous label expansions planned that could offset Humira sales declines. Some investors are skeptical over whether it will be enough.

- Ultimately, the lack of visibility on Humira's growth trajectory prevents most of the street from turning more positive. 4Q18 Humira performance will be closely watched.