TOFACITINIB SOLN,ORAL
Clinical Criteria Summary
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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
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Indication & Patient Population
- Treatment of adult patients with active ankylosing spondylitis (AS)
- Patients must have had an inadequate response or intolerance to one or more tumor necrosis factor inhibitors (TNFIs)
- Active AS defined by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and BASDAI back pain score ≥ 4 despite ≥ 2 NSAIDs, or intolerance to NSAIDs
Dosing & Administration
- Immediate-release: 5 mg twice daily
- Extended-release: 11 mg once daily
- Dose reduction required for patients receiving strong CYP3A4 inhibitors (e.g., ketoconazole) or moderate CYP3A4 inhibitors with a strong CYP2C19 inhibitor (e.g., fluconazole): immediate-release 5 mg once daily
- Dose reduction required for patients with moderate and severe renal impairment or moderate hepatic impairment: immediate-release 5 mg once daily
- Stable background therapies allowed: NSAIDs, methotrexate (≤ 25 mg/week), sulfasalazine (≤ 3 g/day), and oral glucocorticoids (≤ 10 mg/day prednisone equivalent)
Contraindications & Limitations of Use
- Not recommended for use in combination with biologic disease modifying antirheumatic drugs (DMARDs) or potent immunosuppressants such as azathioprine and cyclosporine
- Patients with current or prior treatment with targeted synthetic DMARDs (including JAK inhibitors) and current biologic DMARD therapy are excluded
Place in Therapy & Sequence of Use
- Conditionally recommended as second-line therapy after TNFIs or IL-17AIs for active AS with inadequate response or intolerance to NSAID therapy
- Conditionally recommended as third-line therapy after IL-17AIs for active AS after primary nonresponse to TNFI
- Conditionally recommended against for active AS in secondary nonresponders to TNFI
Safety & Vaccination Requirements
- Live vaccines should be administered at least 2 weeks prior to initiation of tofacitinib therapy
- All patients should complete the two-dose series of recombinant zoster vaccine (SHINGRIX) before becoming immunosuppressed
- If initiated before herpes zoster vaccination, vaccine series should preferably be given when immune response is likely strong and at least in process by the end of the first year of treatment
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Infections
- Exclusion: Active, serious, systemic or localized infection, including undrained abscess (may start/restart once controlled)
- Exclusion: Untreated latent or active tuberculosis infection
- Exclusion: Untreated HIV infection (treated, well-controlled, asymptomatic HIV-positive patients may be treated)
Malignancy & Cardiovascular Risk
- Exclusion: Malignancy within the previous 5 years other than successfully treated nonmelanoma skin cancer or successfully treated cervical cancer
- Exclusion: At increased risk of thrombosis or major adverse cardiovascular events where potential harms are expected to outweigh anticipated benefits
Laboratory & Hematologic Parameters
- Exclusion: Lymphocytes < 500 cells/mm3, neutrophils < 1000 cells/mm3, or hemoglobin < 9 g/dL (may start/restart once resolved; requires confirmation by repeat testing)
Hepatic Screening & Management
- Exclusion: Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis)
- Exclusion: HBsAg-negative but antibody-to-hepatitis-B-core-antigen (anti-HBc)-positive and not on antiviral prophylaxis (may initiate after starting prophylaxis; consultation with hepatologist or infectious diseases expert recommended)
- Inclusion: Current or past completion of hepatitis C screening (may initiate while waiting for results)
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 overlaps during treatment transition]
- Exclusion: Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation
Pregnancy & Lactation
- Exclusion: Pregnancy and females of reproductive potential not using adequate contraception
- Exclusion: Breastfeeding, unless breastfeeding occurs at least 18 hours after the most recent dose
Diagnosis, Monitoring & Prescribing Requirements
- Inclusion: Prescribed and monitored by a VA/VA Community Care rheumatologist, dermatologist, or locally designated expert
- Inclusion: Tofacitinib prescribed at the FDA-recommended dose for psoriatic arthritis, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias
- Inclusion: Inflammatory articular disease (joint, spine, and/or entheseal) and a definite or provisional diagnosis of active psoriatic arthritis
- 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: ONE tumor necrosis factor inhibitor (TNFI) is medically inadvisable, not tolerated, or not adequate after 3 months
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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
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Diagnosis & Indication
- Current or prior moderate to severe ulcerative colitis (UC) confirmed by endoscopy or imaging.
- Prescribed and monitored by a VA/VA Community Care gastroenterologist/hepatologist or locally-designated expert.
Screening & Laboratory Requirements
- Completed tuberculosis (TB) test using tuberculin skin test or interferon-gamma release assay (IGRA).
- Completed hepatitis B screening (at minimum, 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.
- Routine retesting is not required for prescription renewals; retesting in high-risk patients should be considered.
Exclusion Criteria
- Uncontrolled, active, severe infection including evidence of C. difficile and undrained abscess (may start/restart once infection treatment initiated).
- Untreated latent or active tuberculosis infection.
- Hepatitis B surface antigen (HBsAg)-positive and not on antiviral prophylaxis (may initiate after starting 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, unless treating gastroenterologist and oncologist agree risk-benefits favor use.
- 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 resolved).
- 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.
- Lactation/providing breastmilk to an infant unless it occurs at least 18 hours after the most recent dose.
- Concomitant live or live-attenuated vaccines or administration of inactivated, live, or live-attenuated vaccines less than 2 weeks before initiation.
Treatment History & Sequencing (Additional Inclusion Criteria)
- 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.
Special Populations & Counseling
- If HBsAg-negative but anti-HBc-positive: 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 women who can become pregnant: Pregnancy status verified. Counseling provided on potential risks vs benefits of treatment and the use of effective contraception.
Dosing & Monitoring
- Prescribe at the FDA-recommended dose for UC, adjusting for CYP3A4 drug interactions, moderate or severe renal impairment, moderate hepatic impairment, and hematocytopenias.
- Discontinue if no response after 16 weeks of induction with tofacitinib 10 mg twice daily (or extended-release tofacitinib 22 mg once daily).
- Patients achieving response or remission should have dose reduced to 5 mg twice daily (or 11 mg once daily of extended-release tofacitinib) and use the lowest effective dose needed to maintain response.
- Use of higher induction doses beyond induction should be limited to patients with loss of response for the shortest duration clinically feasible.