JAK Inhibitors

Fast-acting oral medicines for moderate to severe ulcerative colitis and Crohn’s disease. This article focuses on tofacitinib and upadacitinib, how they work, who they may help, how they are taken, and key safety steps that matter before and during treatment.

JAK inhibitors calm inflammation by blocking Janus kinase signaling inside immune cells. They are pills, not injections. Many people notice symptom relief within days to weeks. Serious risks exist, so careful screening and monitoring are required. (gastro.org)

Key takeaways

• Upadacitinib is FDA‑approved for adult ulcerative colitis and Crohn’s disease; tofacitinib is approved for adult ulcerative colitis only. (fda.gov)

• Onset is fast. Tofacitinib improved rectal bleeding and stool frequency by day 3 in trials. Upadacitinib showed clinical response as early as week 2. (pubmed.ncbi.nlm.nih.gov)

• The class carries boxed warnings for serious infections, blood clots, major cardiovascular events, certain cancers, and death. Risk is higher in older adults and current or past long‑term smokers. (fda.gov)

• Vaccines and labs are essential. Screen for TB and hepatitis. Give recombinant shingles vaccine if possible before starting. Check CBC, liver tests, and lipids after starting. (xeljanz.pfizerpro.com)

• As of October 13, 2025, the FDA expanded the upadacitinib IBD indication to allow use after at least one systemic therapy if TNF blockers are clinically inadvisable. Coverage policies may still require step therapy. (prnewswire.com)

What are JAK inhibitors

JAK inhibitors are targeted synthetic medicines that block intracellular signals that drive inflammation. In IBD, they can reduce symptoms quickly and help heal the bowel lining over time. Upadacitinib targets JAK1 preferentially. Tofacitinib targets JAK1 and JAK3. These differences may affect dosing and lab effects, but both require the same safety screening. (news.abbvie.com)

Who are they for

• Ulcerative colitis: Both tofacitinib and upadacitinib are options for adults with moderate to severe disease. The AGA living guideline lists both among effective advanced therapies. In practice, FDA labeling and insurance often influence sequence. (gastro.org)

• Crohn’s disease: Upadacitinib is approved for induction and maintenance in adults. Tofacitinib did not meet endpoints in phase 2 Crohn’s studies and is not approved for Crohn’s. (fda.gov)

How fast do they work

• Tofacitinib: Post‑hoc analyses show improvement in stool frequency and rectal bleeding by day 3 of induction. (pubmed.ncbi.nlm.nih.gov)

• Upadacitinib: In Crohn’s disease, response and endoscopic improvement were superior to placebo by week 12, with symptom improvement seen as early as week 2 in induction trials. In ulcerative colitis, similar rapid improvements were seen. (fda.gov)

How are they taken

Safety and key risks

All JAK inhibitors carry boxed warnings. The FDA found increased risks of serious heart‑related events, certain cancers, blood clots, and death in a large safety trial with tofacitinib. The warnings now apply to this class, including upadacitinib. Extra caution is advised in people 65 or older, current or past long‑term smokers, and those with cardiovascular risk. Use the lowest effective dose. (fda.gov)

Serious infections can occur, including shingles, pneumonia, TB, and fungal infections. Stop treatment during serious infection until controlled. Upadacitinib has rare reports of gastrointestinal perforation, especially with risk factors like diverticulitis or concurrent NSAIDs or steroids. (drugs.com)

Screening, vaccines, and monitoring

Before starting either medicine:

• Screen for TB and hepatitis B and C. Update routine vaccines. Avoid live vaccines during therapy. (xeljanz.pfizerpro.com)

• Give recombinant zoster vaccine (Shingrix) to immunocompromised adults 19 years or older, ideally before therapy. Two doses are required. (cdc.gov)

After starting:

• Tofacitinib: Check CBC, hemoglobin, and neutrophils at baseline, at 4 to 8 weeks, then every 3 months. Check liver tests periodically. Check lipids at 4 to 8 weeks. (xeljanz.pfizerpro.com)

• Upadacitinib: Check CBC and liver tests at baseline and periodically. Check lipids around 12 weeks, then per guidelines. Hold treatment for severe lab abnormalities. (rinvoqhcp.com)

Drug interactions and practical tips

• Strong CYP3A4 inhibitors change upadacitinib dosing during induction and maintenance. Check the label if using azole antifungals, clarithromycin, or certain antivirals. (drugs.com)

• Strong CYP3A4 inhibitors or combined moderate CYP3A4 plus strong CYP2C19 inhibitors require tofacitinib dose reductions. Avoid strong CYP3A4 inducers that may lower exposure. (pfizermedical.com)

• Do not combine JAK inhibitors with biologics or other potent immunosuppressants. (fda.gov)

Where they fit in treatment

Guidelines list both agents as effective options for moderate to severe ulcerative colitis, with higher relative efficacy seen for upadacitinib in some analyses, particularly after prior biologic exposure. For Crohn’s disease, upadacitinib is recommended for induction and maintenance in adults, including after anti‑TNF exposure. Access is shaped by FDA labeling and insurer policies. (gastro.org)

Special situations

• Pregnancy and breastfeeding: Both drugs should be avoided in pregnancy when possible. Effective contraception is advised during therapy and for about 4 weeks after the last dose. Breastfeeding is not recommended while taking JAK inhibitors, and for a short window after the last dose per product guidance. Discuss timing if planning pregnancy. (drugs.com)

• Blood clots or heart disease history: Many clinicians avoid JAK inhibitors in people with prior VTE, strong cardiovascular risk, or active cancer, unless benefits clearly outweigh risks. Shared decision making is essential. (fda.gov)

FAQs

Can JAK inhibitors be used with biologics

They are not used with biologics or other potent immunosuppressants because of infection and safety risks. (fda.gov)

How soon should improvement be expected

Many patients notice symptom relief within 1 to 2 weeks. Some tofacitinib users improved by day 3 in trials. Endoscopic healing takes longer. (pubmed.ncbi.nlm.nih.gov)

Are there situations to stop or pause therapy

Yes. Pause during serious infection, with very low blood counts, marked anemia, suspected drug‑induced liver injury, or a blood clot. Restart only after evaluation. (rinvoqhcp.com)

Does upadacitinib help Crohn’s disease

Yes. The FDA approved upadacitinib for adult Crohn’s disease in May 2023. Induction is 45 mg daily for 12 weeks, then 15 mg daily for maintenance, with 30 mg for select refractory cases. (fda.gov)

What about insurance and sequencing

As of October 13, 2025, the FDA allows earlier upadacitinib use when TNF blockers are not advisable after at least one systemic therapy. Health plans may still require step therapy, which varies by plan. (prnewswire.com)