Table 3.

Benefits and Risks of Biologics vs JAK Inhibitors

Medication	Benefits	Risks	Convenience/Desirability	Comments
Biologics	More precise targeting than immunosuppressants and oral JAK inhibitors No lab monitoring required	Associated pain, risk of injection site reaction	Requires refrigeration and special shipping	All AD biologics administered subcutaneously
Dupilumab	High efficacy for inflammation and itch No increased risk of systemic infection Fewer skin infections Excellent safety to date Requires no lab monitoring Available for 6 months and older with AD	Conjunctivitis Red face syndrome reported in real-life experience, but not trials Rare arthritis Rare psoriasiform dermatitis	Given every 2–4 wks Pain with injection	Longest duration of experience in AD Only new systemic medication shown to be efficacious for other atopic disorders and thus can have potential benefits on other atopic conditions
Tralokinumab	Moderate efficacy for inflammation and itch No increased risk of systemic infection or herpes Fewer skin infections High safety to date Requires no lab monitoring	Excellent safety- Conjunctivitis is adverse event but may be less than with dupilumab	Given every 2–4 wks Usually 2 syringes per dose Pain with injection	Although no head-to-head trials, phase 3 trial results suggest lower efficacy short-term than dupilumab or lebrikizumab Efficacy improves with time Only available for adults
Lebrikizumab	High efficacy for inflammation and itch No increased risk of systemic infection or herpes Fewer skin infections High safety to date Requires no lab monitoring	Conjunctivitis is adverse event	Given every 2–4 wks Pain with injection	Not yet FDA-approved
Nemolizumab	High efficacy for itch in some studies	High creatine kinase levels Possible worsening or new onset asthma	Given every 4 wks	Not yet FDA-approved Lower efficacy for inflammation than other biologics Role in treating AD is unclear, given availability of other biologics with greater anti-inflammatory efficacy Only published phase 3 study from Japan and 60mg dosing (vs 30mg in ongoing studies)
JAK Inhibitors	Small molecule inhibitors with rapid clearance	Require lab monitoring All with boxed warning based on tofacitinib data (malignancy, thrombosis, cardiovascular issues, serious infections, death)	Oral Easy to stop and start (eg, for short-term/seasonal use) Multiple doses available to tailor to patient needs	Broader range of effects, which means potential value for other concomitant non-atopic disorders (eg alopecia areata and vitiligo), but also higher risk for side effects
Baricitinib	Currently FDA-approved for adults with alopecia areata (4mg) More modest efficacy than other JAK inhibitors, but also fewer tolerability issues	Boxed warning Not as targeted as JAK1 selective medications but less adverse events than other JAKi in trials Headache, nasopharyngitis, increased infections, including herpetic	Daily administration Does not require refrigeration	Not FDA-approved for AD (approved in Europe)
Abrocitinib	High efficacy suggests use for severe AD Flexibility in dosing – start at 100mg daily and can increase to 200mg daily	Boxed warning Nausea/vomiting, headache, nasopharyngitis, infections, including herpes simplex and zoster, acne Abnormal platelet counts, increased transaminases, high creatine kinase, hyperlipidemia	Daily administration Easy to stop and start Does not require refrigeration	12-week head-to-head trial in adults suggests that only 200mg dose is more efficacious than dupilumab 300mg every 2 wks for itch (and not for IGA 0/1/EASI-75)
Upadacitinib	High efficacy suggests use for severe AD Flexibility in dosing – start at 15mg daily and can increase to 30mg daily	Boxed warning Acne, headache, nasopharyngitis, infections, including herpes simplex and zoster Abnormal blood counts, increased transaminases, high creatine kinase, hyperlipidemia	Daily administration Easy to stop and start Does not require refrigeration	16-week head-to-head trial in adults suggests that 30mg dose is more efficacious than dupilumab 300mg every 2 wks