What is on and off treatment?

Understanding "On Treatment" and "Off Treatment" States

"On treatment" and "off treatment" are clinical states that describe whether a patient is actively receiving therapeutic medication, with critical implications for disease control, recurrence risk, and treatment monitoring across multiple medical conditions.

Core Definitions

On Treatment State

• Patients are actively receiving therapeutic medication at doses intended to control their disease 1
• This state is associated with lower risks of disease recurrence or progression compared to being off treatment 1
• Patients remain in this state until they experience complications requiring discontinuation (such as major bleeding or intracranial hemorrhage) or until treatment is intentionally stopped 1

Off Treatment State

• Patients have discontinued active therapy either temporarily or permanently 1
• This transition occurs after:
  • Major adverse events (intracranial hemorrhage, major bleeding) 1
  • Achievement of treatment goals (complete remission) 1
  • Patient/physician decision to discontinue 1
  • Treatment failure or intolerance 1

Context-Specific Applications

In Anticoagulation Therapy

• On treatment: Patients receiving anticoagulants with lower VTE recurrence risk 1
• Off treatment: Significantly elevated recurrence risk that varies by time from initial thrombotic event 1
• Patients typically transition off treatment after major bleeding complications 1

In Autoimmune Blistering Diseases (Bullous Pemphigoid/Mucous Membrane Pemphigoid)

Complete remission off therapy is defined as absence of new or established lesions while off all therapy for at least 2 months 1

Complete remission on therapy means absence of lesions while receiving minimal maintenance therapy for at least 2 months 1

• Minimal therapy thresholds include:
  • Prednisone ≤0.1 mg/kg/day 1
  • Clobetasol propionate ≤20 g/week 1
  • Specific low-dose immunosuppressants (azathioprine ≤0.7-1.0 mg/kg/day, mycophenolate mofetil ≤500 mg/day, methotrexate ≤5 mg/week, dapsone ≤50-100 mg/day) 1

In Prostate Cancer (Androgen Deprivation Therapy)

Intermittent ADT involves planned cycling between on-treatment and off-treatment periods 1

• Off-treatment intervals provide:
  • Reduced treatment side effects 1
  • Quality-of-life benefits 1
  • Lower costs 1
• Patients require close monitoring even during off-treatment periods with frequent follow-up visits 1

In Chronic Hepatitis B

Sustained off-therapy response represents the ideal endpoint 1, 2

• For HBeAg-positive patients: Sustained HBeAg seroconversion with HBV DNA <2000 IU/mL and ALT normalization off therapy 1, 2
• For HBeAg-negative patients: Sustained HBV DNA reduction and ALT normalization off therapy, though this is rarely achieved 1, 2
• Critical caveat: Even after achieving off-therapy endpoints, patients with significant fibrosis or cirrhosis require lifelong HCC screening 2

In Parkinson's Disease

"OFF episodes" refer to periods when medication effect wears off, causing return of parkinsonian symptoms 3, 4, 5, 6

• These are not the same as being "off treatment" but rather represent fluctuations in medication response 3, 4, 5
• OFF time includes both:
  • Wearing OFF: End-of-dose deterioration 6
  • Delayed ON/No ON: Delays in medication taking effect, which may comprise more than twice the OFF time as wearing OFF 6

Clinical Monitoring Implications

Risk Stratification

• Higher disease recurrence/reactivation risk exists in off-treatment states across most conditions 1, 2
• Time-varying risk: The longer patients remain off treatment from their initial disease event, the higher their recurrence risk 1

Switching Between Therapies

• Washout periods (being temporarily off treatment) are required when switching between immunosuppressive therapies 7, 8
• Traditional recommendation: Four times the drug's terminal half-life to minimize immunosuppressive burden 7, 8
• For biologics specifically: 3-month washout period before initiating new biologic therapy 7, 8

Monitoring Requirements

• Off-treatment patients require intensified surveillance for disease reactivation 2
• Regular blood tests and clinical assessments are mandatory, particularly in the first year after discontinuation 2

Important Clinical Pitfalls

• Do not assume "off treatment" always means treatment failure - it may represent successful achievement of remission endpoints 1, 2
• Overlapping immunosuppressive therapies should be avoided when transitioning between on-treatment states with different agents due to infection risk 7, 8
• Disease rebound is a significant concern when discontinuing certain therapies, particularly biologics, requiring careful transition planning 7
• Patient adherence to monitoring is critical even during planned off-treatment intervals, as in intermittent ADT 1