What is a typical triple therapy regimen?

Triple Therapy Regimens

The term "triple therapy" refers to different treatment combinations depending on the clinical context, with the most common being: (1) protease inhibitor + pegylated interferon + ribavirin for hepatitis C, (2) oral anticoagulant + aspirin + P2Y12 inhibitor for patients with atrial fibrillation undergoing PCI, and (3) inhaled corticosteroid + long-acting β-agonist + long-acting muscarinic antagonist for COPD.

Hepatitis C Triple Therapy

For treatment-naïve genotype 1 hepatitis C patients, triple therapy consists of a protease inhibitor (telaprevir or boceprevir) combined with pegylated interferon and ribavirin. 1

Telaprevir-Based Regimen

• 12 weeks of telaprevir plus pegylated interferon-alpha and ribavirin, followed by 32 weeks of pegylated interferon-ribavirin alone (total 48 weeks) 2
• In the ADVANCE trial, this regimen achieved 75% SVR rates compared to 44% with standard dual therapy alone 1
• No lead-in phase is used with telaprevir 1

Boceprevir-Based Regimen

• 4-week lead-in phase of pegylated interferon-ribavirin, followed by 32 weeks of boceprevir triple therapy, then 12 weeks of pegylated interferon-ribavirin (total 48 weeks) 2
• The SPRINT-2 trial demonstrated 66% SVR rates with this approach versus 38% with standard therapy 1
• The lead-in phase increases rapid virological response rates and allows treatment duration shortening to 28 weeks in responders 1

Patient Selection Criteria

• Triple therapy should be initiated quickly in patients with severe fibrosis (F3-F4), is indicated for moderate fibrosis (F2), and considered case-by-case for mild fibrosis 2
• For relapsers after prior pegylated interferon-ribavirin therapy, triple therapy achieved 83-88% SVR rates 1
• For partial responders, SVR rates were 40-59% 1
• For null responders with severe fibrosis, triple therapy achieved approximately 15% SVR in F4 patients and 40% in F3 patients 2

Cardiovascular Triple Therapy (Atrial Fibrillation + PCI)

For patients with atrial fibrillation requiring oral anticoagulation who undergo PCI, triple therapy consists of oral anticoagulant + aspirin + clopidogrel, but should be limited to the shortest necessary duration.

Duration Recommendations

• 1 month of triple antithrombotic therapy is recommended irrespective of stent type used 1
• May be extended up to 6 months in patients at high ischemic risk due to ACS or complex anatomical/procedural characteristics that outweigh bleeding risk 1
• After completing triple therapy, transition to dual antithrombotic therapy (oral anticoagulant + aspirin or clopidogrel) up to 12 months, followed by oral anticoagulant alone 1

Important Caveats

• Ticagrelor or prasugrel are NOT recommended as part of triple antithrombotic therapy—only clopidogrel should be used 1
• When rivaroxaban is used, the 15-mg once-daily dose may be used instead of the conventional 20-mg dose 1
• Target INR should be maintained at 2-2.5 (lower end of therapeutic range) when warfarin is used 1
• Proton pump inhibitors should be used routinely to reduce gastrointestinal bleeding risk 1

COPD Triple Therapy

For chronic obstructive pulmonary disease, triple therapy consists of an inhaled corticosteroid + long-acting β-agonist + long-acting muscarinic antagonist.

Indications

• Recommended for patients who experience recurrent exacerbations despite dual bronchodilator therapy or LABA/ICS combination 3
• Earlier initiation of triple therapy in patients at high risk of acute exacerbation provides net benefit, with a gain of 4.8 quality-adjusted life-years per 100 patients over 20 years 4
• Each 30-day delay in triple therapy initiation after COPD hospitalization increases the odds of any exacerbation by 13% and severe exacerbation by 10% 5

Patient Selection

• Greatest benefit in patients with high symptom burden (modified Medical Research Council dyspnea scale score >1), with net QALY gain of 5.9 per 100 patients 4
• Prompt initiation (within 30 days) following hospitalization for COPD exacerbation reduces subsequent exacerbations and healthcare costs 5

Lupus Nephritis Triple Therapy

For proliferative lupus nephritis, triple therapy consists of standard-of-care (mycophenolate or cyclophosphamide + corticosteroids) plus either belimumab or a calcineurin inhibitor (voclosporin). 1

Belimumab-Based Triple Therapy

• More effective in patients with proteinuria <3 g/day 1
• May decrease rate of severe flares and slow decline of kidney function 1
• Can be used if GFR is at least 30 ml/min per 1.73 m² 1
• Most effective on background of mycophenolate; uncertain effectiveness with cyclophosphamide 1

Calcineurin Inhibitor-Based Triple Therapy

• May be considered in patients with relatively good kidney function (eGFR ≥45 ml/min per 1.73 m²) who have heavy proteinuria due to podocyte injury 1
• Voclosporin is oral only, whereas belimumab requires intravenous/subcutaneous administration 1
• Use cautiously if GFR is impaired (e.g., <45 ml/min per 1.73 m²) 1