TOFACITINIB TAB,SA

Diagnosis & Monitoring

• Definite or provisional diagnosis of active ankylosing spondylitis (or radiographic axial spondyloarthritis)
• Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
• Routine retesting for tuberculosis and hepatitis screening is not required for prescription renewals; consider retesting in high-risk patients

Active Infection & Immunodeficiency

• Exclusion: Uncontrolled active infection (initiation/restart permitted once treatment for the infection is initiated)
• Exclusion: Untreated latent or active tuberculosis infection
• Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (initiation permitted after starting prophylaxis)
• Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
• Exclusion: Congenital or acquired immunodeficiency
• Inclusion: Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
• Inclusion: Completed hepatitis B screening (at minimum, HBsAg, total anti-HBc and anti-HBs)
• Inclusion: Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
• Additional: If HBsAg-negative but anti-HBc-positive with consult deemed indicated, GI/liver or infectious diseases expert must advise on antiviral prophylaxis or preemptive monitoring for HBV reactivation

Malignancy

• Exclusion: Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless rheumatologist and oncologist agree that risk-benefits favor using the drug)

Hematologic & Hepatic Parameters

• Exclusion: Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (initiation/restart permitted once lymphopenia, neutropenia, and/or anemia resolve)
• Exclusion: Severe hepatic impairment (Child-Pugh class C)

Cardiovascular Risk

• Exclusion: At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh the anticipated benefits

Concomitant Medications & Vaccines

• Exclusion: Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin) (except during treatment transition overlaps)
• Exclusion: Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
• Inclusion: Offered all age-appropriate vaccinations prior to initiating therapy
• Note: Recombinant zoster vaccine should be completed or at least initiated by the end of the first year, preferably when dosage is low, disease is stable, or at other times when a robust immune response to vaccination can be expected

Pregnancy, Lactation & Counseling

• Exclusion: Pregnancy
• Exclusion: Breastfeeding
• Additional Inclusion (Females who can become pregnant): Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
• Additional Inclusion (Females who are breastfeeding/providing breastmilk to an infant): Counseling provided on potential risks vs benefits of treatment

Prior Therapy Requirements

• Inclusion: ONE tumor necrosis factor inhibitor (TNFI) is medically inadvisable, not tolerated, not adequate after 3 months, or lost response
• Note: Criteria apply only to new starts; patients on tofacitinib who are stable (responded after 16 weeks and/or controlled on maintenance therapy) should not be switched to a criteria-required prior drug for nonmedical reasons

Dosing & Administration Considerations

• Prescribed at the FDA-recommended dose for ankylosing spondylitis, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
• Use with extreme caution in patients 65 years or older due to higher risks of serious infections, fatal infection, and possibly increased mortality

Criteria for TOFACITINIB SOLN,ORAL and TOFACITINIB TAB,ORAL (Psoriatic Arthritis Indication)

Exclusion Criteria

• Active infection (may initiate/restart once treatment for the infection is initiated)
• Untreated latent or active tuberculosis infection
• Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
• Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
• Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer
• At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
• Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (may start/restart once lymphopenia, neutropenia, and/or anemia resolve)
• Severe hepatic impairment (Child-Pugh class C)
• Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin)
• Pregnancy and females of reproductive potential not using adequate contraception
• Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation of tofacitinib therapy

Inclusion Criteria

• Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally designated expert
• Has inflammatory articular disease (joint, spine, and/or entheseal) and a definite or provisional diagnosis of active psoriatic arthritis
• Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
• Completed hepatitis B screening (HBsAg, total hepatitis B core antibody [anti-HBc] and antibody to hepatitis B surface antigen [anti-HBs])
• Current or past completion of hepatitis C screening (may initiate while waiting for test results)
• ONE tumor necrosis factor inhibitor (TNFI) is medically inadvisable, not tolerated, or not adequate (i.e., NO or partial response after 12 weeks or loss of initial response)

Additional Inclusion Criteria

• If HBsAg-negative but anti-HBc-positive and consult deemed indicated: GI/liver or infectious diseases expert has been consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation
• For females who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception
• For females who are breastfeeding/providing breastmilk to an infant: Advised to avoid breastfeeding during treatment and for at least 18 hours after the last dose of tofacitinib (or 36 hours after sustained-action tofacitinib); counseling provided on potential risks vs benefits

Sequencing & Clinical Management Considerations

• Applies to new starts only; patients on treatment who are stable should not be switched to a criteria-required prior treatment for nonmedical reasons
• Sequencing therapies for active psoriatic arthritis: 1L csIMM (for predominantly peripheral arthritis, no axial disease, no severe psoriasis, no IBD/uveitis) or TNFi; 2L IL-17i (ixekizumab preferred) or JAKi; 3L IL-12/23i or IL-23i (not for axial disease); 4L Abatacept (not for axial disease); Other: Apremilast, Deucravacitinib
• Routine rescreening is not required for prescription renewals; retesting in high-risk patients should be considered
• Vaccinations should be updated before initiation when possible; recombinant zoster vaccine should be completed or at least initiated by the end of the first year of treatment, preferably when dosage is low, disease is stable, or a robust immune response can be expected

Exclusion Criteria

• Uncontrolled active infection (initiation/restart permitted once treatment for the infection is initiated)
• Untreated latent or active tuberculosis infection
• Hepatitis B surface antigen (HBsAg)-positive without antiviral prophylaxis (initiation permitted after starting prophylaxis)
• HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive without antiviral prophylaxis (initiation permitted after starting prophylaxis)
• Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients are eligible)
• Congenital or acquired immunodeficiency
• Malignancy within the previous 5 years, excluding successfully treated nonmelanoma skin cancer or cervical cancer (unless treating rheumatologist and oncologist agree risk-benefits favor use)
• Increased risk of thrombosis or major adverse cardiovascular events where potential harms outweigh anticipated benefits
• Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (initiation/restart permitted once cytopenias resolve)
• Severe hepatic impairment (Child-Pugh class C)
• Concomitant therapy with biologic disease-modifying antirheumatic drugs (bDMARDs), other immunosuppressive biologics, potent immunosuppressants (e.g., azathioprine, cyclosporine, tacrolimus), or strong CYP3A4 inducers (e.g., rifampin)
• Pregnancy
• Breastfeeding (unless occurring at least 18 hours after the most recent dose)
• Concomitant live or live-attenuated vaccines, or administration of inactivated/live/live-attenuated vaccines less than 2 weeks before initiation

Inclusion Criteria

• Prescribed and monitored by a VA/VA Community Care rheumatologist or locally designated expert
• Moderate to severe active rheumatoid arthritis
• FDA-recommended dose for rheumatoid arthritis, with adjustments for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
• Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA)
• Offered all age-appropriate vaccinations prior to initiating therapy
• Completed hepatitis B screening (at minimum: HBsAg, total anti-HBc, and antibody to hepatitis B surface antigen [anti-HBs])
• Current or past completion of hepatitis C screening (initiation permitted while awaiting results)
• Tumor necrosis factor inhibitor (TNFi) therapy is medically inadvisable, not tolerated, not adequate (no response to one TNFI after 3 months, partial response to 3-month trials of two TNFIs totaling 6 months), or lost response

Clinical Precautions & Monitoring Guidelines

• Extreme caution required for patients 65 years or older due to higher risks of serious infections, fatal infection, and possibly increased mortality
• Antiviral prophylaxis for HBV should utilize agents with a high genetic barrier to resistance (e.g., entecavir or tenofovir)
• Vaccinations should be updated prior to initiation when possible; recombinant zoster (SHINGRIX) vaccine should be completed or initiated by the end of the first year, preferably at low dosage, stable disease, or during periods expected to yield a robust immune response

Criteria for Tofacitinib (SOLN,ORAL / TAB,ORAL / TAB,SA) - Ulcerative Colitis

Exclusion Criteria

• Active infection (may start/restart once treatment for the infection is initiated)
• Untreated latent or active tuberculosis infection
• Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting antiviral prophylaxis)
• Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
• Congenital or acquired immunodeficiency
• Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer (unless treating gastroenterologist and oncologist agree that risk-benefits favor using the drug)
• At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
• Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (may start/restart once lymphopenia, neutropenia and/or anemia resolve)
• Severe hepatic impairment (Child-Pugh class C)
• Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation of tofacitinib therapy
• Concomitant JAK inhibitors, biologic immunomodulators, potent immunosuppressants (e.g., azathioprine and cyclosporine)
• Concomitant strong CYP3A4 inducers (e.g., rifampin)
• Pregnancy and females of reproductive potential not using adequate contraception
• Breastfeeding/providing breastmilk to an infant during treatment and for at least 18 hours after the last dose of tofacitinib (or 36 hours after last dose of sustained-action tablet [TOFACITINIB TAB,SA])

Inclusion Criteria

• Prescribed and monitored by a VA/VA Community Care gastroenterologist or locally designated expert
• Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging
• Offered all age-appropriate vaccinations prior to initiating therapy
• Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay [IGRA]
• Completed hepatitis B screening (HBsAg, total antibody-to-hepatitis-B-core-antigen [anti-HBc], and antibody to hepatitis B surface antigen [anti-HBs])
• Current or past completion of hepatitis C screening (may initiate while waiting for test results)

Additional Inclusion Criteria (One must be selected)

• Tumor necrosis factor inhibitor (TNFI) is medically inadvisable (Infliximab/biosimilar is the preferred TNFI in UC)
• Primary nonresponse, inadequate partial response, or loss of response after 12 weeks of one TNFI in the presence of adequate TNFI levels (mechanistic failure)
• Loss of response to a TNFI despite therapeutic drug monitoring (TDM)-based optimized dosing to address pharmacokinetic failure (Infliximab/biosimilar is the preferred TNFI)
• Ustekinumab is medically inadvisable, inadequate, not tolerated, or lost response

Additional Inclusion Criteria (Select if applicable)

• If HBsAg-negative but anti-HBc-positive and consult deemed indicated: A GI/liver or infectious diseases expert has been consulted for advice on whether to start antiviral prophylaxis or to preemptively monitor for HBV reactivation
• For females who can become pregnant: Pregnancy status verified; counseling provided on potential risks vs benefits of treatment and the use of effective contraception
• For females breastfeeding/providing breastmilk: Counseling provided on potential risks vs benefits of treatment

Dosing, Monitoring, & Sequencing Considerations

• Prescribed at the FDA-recommended dose for ulcerative colitis, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
• Use with extreme caution in patients 65 years or older due to higher risks of serious infections, fatal infection, and possibly increased mortality
• Routine retesting is not required for prescription renewals; retesting in high-risk patients should be considered
• Applies only to new starts; patients on tofacitinib who are stable (responded to induction and/or controlled on maintenance therapy) should not be switched to a criteria-required prior drug for nonmedical reasons
• Sequencing: 1L includes Infliximab (preferred), adalimumab, or ustekinumab; Vedolizumab may be used 1L for “moderate” UC, absence of extraintestinal manifestations, or pouchitis. 2L includes Vedolizumab, or either tofacitinib or upadacitinib after TNFi. 3L includes Guselkumab, risankizumab, or either etrasimod or ozanimod. 4L includes Mirikizumab