Infliximab
Remicade and biosimilars (Inflectra, Renflexis, Avsola, Ixifi)
Infliximab — Approved Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Rheumatoid arthritis — moderate to severe | Adults | In combination with methotrexate (required) | FDA Approved |
| Crohn’s disease — moderate to severe (including fistulising) | Adults and ≥6 years | Monotherapy or adjunctive | FDA Approved |
| Ulcerative colitis — moderate to severe | Adults and ≥6 years | Monotherapy or adjunctive | FDA Approved |
| Ankylosing spondylitis | Adults | Monotherapy | FDA Approved |
| Psoriatic arthritis | Adults | With or without MTX | FDA Approved |
| Plaque psoriasis — chronic severe | Adults | Monotherapy (close monitoring required) | FDA Approved |
Infliximab was the first chimeric anti-TNF-α monoclonal antibody approved in the United States (1998), initially for Crohn’s disease. Its RA indication, approved in combination with methotrexate, was established through the landmark ATTRACT and ASPIRE trials demonstrating inhibition of radiographic progression and improvement in physical function. Unlike adalimumab, infliximab requires concurrent methotrexate for the RA indication per the FDA label, reflecting both the drug’s chimeric (human-murine) structure and the role of MTX in reducing immunogenicity.
Sarcoidosis — refractory pulmonary, ocular, or systemic disease. Evidence quality: Moderate (open-label trials, case series).
Behcet’s disease — severe mucocutaneous and ocular manifestations. Evidence quality: Moderate (retrospective studies, expert consensus).
Pyoderma gangrenosum — refractory to conventional immunosuppressants. Evidence quality: Low (case series, case reports).
Infliximab Dosing by Clinical Scenario
Adult Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| RA — with methotrexate (required) | 3 mg/kg IV at Weeks 0, 2, 6 | 3 mg/kg IV Q8W | 10 mg/kg Q8W or 3–10 mg/kg Q4W | MTX is required per FDA label; dose escalation or interval shortening for incomplete responders Higher doses/frequencies increase serious infection risk |
| Crohn’s disease — adult (including fistulising) | 5 mg/kg IV at Weeks 0, 2, 6 | 5 mg/kg IV Q8W | 10 mg/kg Q8W | Dose escalation for loss of response; consider discontinuation if no response by Week 14 |
| Ulcerative colitis — adult | 5 mg/kg IV at Weeks 0, 2, 6 | 5 mg/kg IV Q8W | 5 mg/kg Q8W | No approved dose escalation in the UC label |
| Ankylosing spondylitis | 5 mg/kg IV at Weeks 0, 2, 6 | 5 mg/kg IV Q6W | 5 mg/kg Q6W | Q6W maintenance (not Q8W) — shorter interval than most other indications |
| Psoriatic arthritis | 5 mg/kg IV at Weeks 0, 2, 6 | 5 mg/kg IV Q8W | 5 mg/kg Q8W | May use with or without MTX |
| Plaque psoriasis — chronic severe | 5 mg/kg IV at Weeks 0, 2, 6 | 5 mg/kg IV Q8W | 5 mg/kg Q8W | Close monitoring required; only for candidates for systemic therapy when other options less appropriate |
Pediatric Dosing
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Pediatric Crohn’s disease (≥6 years) | 5 mg/kg IV at Weeks 0, 2, 6 | 5 mg/kg IV Q8W | 5 mg/kg Q8W | Same weight-based dosing as adults |
| Pediatric UC (≥6 years) | 5 mg/kg IV at Weeks 0, 2, 6 | 5 mg/kg IV Q8W | 5 mg/kg Q8W | Same weight-based dosing as adults |
Infliximab is unique among TNF inhibitors in that the RA starting dose (3 mg/kg) is lower than for all other indications (5 mg/kg). The FDA label mandates concomitant MTX for RA, which reduces anti-infliximab antibody formation and improves trough levels. For incomplete RA responders, the dose can be escalated up to 10 mg/kg or the interval shortened to every 4 weeks, though infection risk increases with higher exposure. Infusion must be administered over at least 2 hours with an in-line filter, and personnel and medications for hypersensitivity reactions must be immediately available.
Pharmacology
Mechanism of Action
Infliximab is a chimeric (human-murine) IgG1κ monoclonal antibody with a molecular weight of approximately 149.1 kDa. It binds with high affinity to both soluble and transmembrane forms of TNF-α, neutralising the cytokine’s ability to engage its cell-surface receptors (TNFR1 and TNFR2). By blocking TNF-α signalling, infliximab downregulates pro-inflammatory cascades in the synovium, intestinal mucosa, and skin. Binding to transmembrane TNF-α can also trigger complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity of TNF-expressing inflammatory cells, contributing to apoptosis of activated macrophages and T cells. Unlike fully human anti-TNF antibodies, infliximab’s murine variable regions contribute to a higher baseline immunogenicity, making concomitant immunomodulator therapy important for sustained efficacy.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | IV infusion; 100% bioavailability; Cmax achieved at end of infusion | IV route ensures complete and immediate delivery; no absorption variability |
| Distribution | Vss 3–6 L; primarily intravascular; linear PK (dose-proportional Cmax) | Low Vd reflects confinement to plasma and interstitial space typical of IgG |
| Metabolism | Proteolytic catabolism; not CYP-metabolised; however, TNF-α normalisation may restore CYP450 activity | No direct CYP interactions; monitor narrow-TI CYP substrates (e.g., warfarin) when initiating |
| Elimination | Median terminal t½ 7.7–9.5 days (single dose, FDA PI); clearance 11–15 mL/h; anti-drug antibodies increase clearance ~2.7-fold | Concomitant MTX/immunomodulators reduce ADA formation and prolong effective drug exposure; half-life may be longer (~14 d) at steady state in pop PK models |
Side Effects
Adverse reaction data below are derived from pooled clinical trials in RA patients receiving 4 or more infusions (FDA PI Table 2; N=1,129 infliximab-treated vs N=350 placebo), unless otherwise stated.
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Infections (overall) | 36% vs 25% placebo | Most commonly respiratory tract (URI, sinusitis, pharyngitis, bronchitis) and UTI; average follow-up 51 vs 37 weeks |
| Nausea | 21% vs 20% placebo | Usually mild; may occur during or after infusion |
| Infusion-related reactions | 20% vs 10% placebo | Includes fever, chills, chest pain, dyspnoea, pruritus, urticaria; most common reason for discontinuation |
| Headache | 18% vs 14% placebo | Can occur during or after infusion; usually self-limiting |
| Upper respiratory infection | >10% | Includes sinusitis and pharyngitis; reflects immunosuppression |
| Abdominal pain | 12% vs 8% placebo | Higher rates (26%) in Crohn’s disease population |
| Diarrhoea | 12% vs 12% placebo | Similar to placebo in RA trials |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Rash | 10% vs 5% placebo | Includes non-specific eruptions; evaluate for paradoxical psoriasis |
| Dyspepsia | 10% vs 7% placebo | Usually mild; symptomatic management |
| Fatigue | 9% vs 7% placebo | May relate to underlying disease activity or infusion |
| Arthralgia | 8% | Can also be a feature of delayed hypersensitivity reactions |
| Bronchitis | 10% vs 9% placebo | Part of the broader respiratory infection pattern |
| Cough | 7% | Evaluate persistent cough for TB or opportunistic infection |
| Urinary tract infection | 6% | Treat promptly; recurrent UTIs warrant further evaluation |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Serious infections (pneumonia, cellulitis, sepsis, abscess) | 5.3% vs 3.4% placebo (1-year RA studies) | Any time during treatment | Discontinue infliximab; initiate appropriate antimicrobials; do not restart until infection fully resolved |
| Tuberculosis (active or reactivation) | 0.4% vs 0% placebo in RA | Weeks to months; often disseminated/extrapulmonary | Screen before and during therapy; treat latent TB before starting; stop infliximab for active TB |
| Invasive fungal infections (histoplasmosis, coccidioidomycosis) | Rare (7 cases in clinical trials) | Variable; consider in endemic regions | Empiric antifungal therapy for febrile patients from endemic areas; discontinue infliximab |
| Severe infusion reactions (anaphylaxis, hypotension, seizures) | <1% of patients | During or within 1 hour of infusion | Stop infusion immediately; administer epinephrine, antihistamines, corticosteroids; permanent discontinuation for anaphylaxis |
| Delayed hypersensitivity (serum sickness-like) | ~1% (higher with re-treatment after drug holiday) | 2–14 days after infusion | Treat with corticosteroids and antihistamines; avoid re-administration |
| Lymphoma | 0.08/100 PY (~3-fold higher than general population) | Months to years | Evaluate unexplained lymphadenopathy or constitutional symptoms; refer to oncology |
| Hepatosplenic T-cell lymphoma (HSTCL) | Very rare | Months to years; mainly young males with IBD on thiopurines | Almost universally fatal; highest risk with concurrent azathioprine/6-MP |
| Hepatotoxicity (acute liver failure, jaundice, cholestasis) | Rare (post-marketing) | Weeks to months | Discontinue if jaundice or ALT ≥5× ULN; some cases required liver transplantation |
| Heart failure (new onset or worsening) | Dose-related (higher at 10 mg/kg) | Weeks to months | Contraindicated at doses >5 mg/kg in moderate/severe CHF (NYHA III/IV); discontinue if CHF worsens |
| Demyelinating disease | Rare | Weeks to months | Discontinue; refer to neurology |
| Lupus-like syndrome | Rare | Months of treatment | Discontinue; syndrome typically resolves |
| HBV reactivation | Rare (carriers at risk; some fatal) | During or months after stopping therapy | Screen all patients before initiation; stop infliximab and start antiviral if reactivation occurs |
| Reason for Discontinuation | Incidence | Context |
|---|---|---|
| Infusion reactions | ~3% | Most common reason overall; all patients recovered after stopping the infusion |
| Serious infections | <1% | Pneumonia, cellulitis most frequent |
| Elevated liver enzymes | Rare | More common with concurrent MTX |
Infusion reactions are the hallmark adverse event distinguishing infliximab from subcutaneous TNF inhibitors. Premedication with acetaminophen, antihistamines, and/or corticosteroids can reduce the frequency and severity of reactions. For mild-to-moderate reactions, the infusion rate can be slowed or temporarily stopped, then cautiously restarted. Serious reactions (<1%) require permanent discontinuation. Patients who develop anti-infliximab antibodies are 2–3 times more likely to experience an infusion reaction, reinforcing the importance of concomitant immunosuppression and regular scheduled dosing without treatment interruptions.
Drug Interactions
Infliximab is not metabolised by CYP450 enzymes and has no conventional pharmacokinetic drug interactions. However, TNF-α suppression can normalise suppressed CYP450 activity in chronically inflamed patients, potentially altering levels of narrow-therapeutic-index CYP substrates. The most significant interactions are pharmacodynamic, relating to additive immunosuppression.
Monitoring
- TB ScreeningBefore initiation; periodically during therapy
RoutineTST or IGRA before starting. Treat latent TB before initiating infliximab. Repeat annually in patients with ongoing risk factors. Monitor for active TB throughout treatment, even if initial screening negative. - Hepatitis BBefore initiation; during and after therapy in carriers
RoutineScreen all patients (HBsAg, anti-HBc, anti-HBs). Carriers require monitoring of HBV DNA and LFTs throughout treatment and for several months after stopping. - Liver FunctionBaseline; periodically
RoutineALT/AST elevations more common with concurrent MTX. Discontinue if jaundice or ALT ≥5× ULN. Severe hepatic reactions including acute liver failure reported post-marketing. - CBCBaseline; then periodically
RoutineMonitor for cytopenias and pancytopenia. Urgently check if persistent fever, bruising, or pallor develops. - Vital Signs During InfusionEvery infusion
RoutineMonitor BP, HR, temperature, and SpO2 during and for at least 1 hour post-infusion. Have emergency medications immediately available. - Signs of InfectionEvery visit
RoutineAssess for fever, cough, weight loss, night sweats, or focal symptoms. Serious infection rate was 5.3% in 1-year RA studies. - Skin ExaminationAnnually
RoutineNMSC incidence raised with TNF blockers. Periodic examination, especially with prior skin malignancy or UV exposure history. - Heart FailureIf pre-existing
Trigger-BasedContraindicated >5 mg/kg in NYHA III/IV. Monitor for worsening dyspnoea, oedema in mild CHF; discontinue if worsening. - Neurological SymptomsIf new symptoms
Trigger-BasedEvaluate new visual changes, numbness, weakness, or seizures for demyelinating disease. Discontinue and refer.
Contraindications & Cautions
Absolute Contraindications
- Doses >5 mg/kg in moderate or severe heart failure (NYHA Class III/IV) — a dose-dependent increase in mortality and hospitalisation was observed in clinical trials at 10 mg/kg in CHF patients (FDA PI).
- Previous severe hypersensitivity reaction to infliximab, any inactive ingredient, or any murine proteins (includes anaphylaxis, hypotension, serum sickness).
Relative Contraindications (Specialist Input Recommended)
- Active serious infection — do not initiate until infection is fully controlled.
- Pre-existing demyelinating disease (MS, optic neuritis) — TNF blockade associated with exacerbation.
- Active or untreated latent TB — must complete or initiate latent TB treatment before starting.
- History of malignancy — risk-benefit evaluation required.
Use with Caution
- Mild heart failure (NYHA I/II) — monitor closely; discontinue if symptoms worsen.
- Elderly patients (≥65 years) — higher serious infection incidence.
- HBV carriers — monitor throughout and after treatment; initiate antiviral if reactivation occurs.
- Pregnancy — infliximab crosses the placenta. Avoid live vaccines in exposed infants for at least 6 months after birth.
- Re-initiation after drug-free interval — higher risk of infusion reactions and antibody formation; consider re-induction carefully.
Serious Infections: Patients treated with infliximab are at increased risk for developing serious infections leading to hospitalisation or death, including tuberculosis, invasive fungal infections, and bacterial, viral, and other opportunistic infections. Infliximab should be discontinued if a serious infection or sepsis develops.
Malignancy: Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers. Post-marketing cases of hepatosplenic T-cell lymphoma have occurred, almost always in young males with IBD receiving concurrent azathioprine or 6-mercaptopurine.
Patient Counselling
Purpose of Therapy
Infliximab works by blocking a protein called TNF-alpha that drives inflammation in conditions like rheumatoid arthritis. By reducing this inflammation, it helps relieve joint pain, stiffness, and swelling, and can slow or stop joint damage when used alongside methotrexate. It is given as an intravenous infusion in a clinic or infusion centre, typically over at least 2 hours.
How to Take
Infliximab is administered by a healthcare professional through an IV drip. For RA, patients typically receive infusions at Weeks 0, 2, and 6 (induction), then every 8 weeks thereafter. Each infusion usually lasts at least 2 hours, with monitoring during and after. Patients should inform their clinician if they feel unwell (fever, chills, chest tightness, difficulty breathing) during or shortly after the infusion.
Sources
- Janssen Biotech, Inc. INFLIXIMAB for injection, for intravenous use. Full Prescribing Information. Revised 10/2021. FDA LabelPrimary source for all dosing, indications, boxed warnings, adverse reaction incidence rates, and pharmacokinetic data.
- Janssen Biotech, Inc. REMICADE (infliximab) for injection. Full Prescribing Information. Janssen LabelMost recent branded Remicade label with updated immunogenicity data using ECLIA methodology.
- Maini R, St Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis factor α monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial (ATTRACT). Lancet. 1999;354(9194):1932-1939. doi:10.1016/S0140-6736(99)05246-0Pivotal phase III trial establishing infliximab + MTX efficacy for RA signs/symptoms and radiographic progression.
- Lipsky PE, van der Heijde DMFM, St Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. N Engl J Med. 2000;343(22):1594-1602. doi:10.1056/NEJM200011303432202ATTRACT 54-week results confirming sustained inhibition of structural damage with infliximab + MTX.
- St Clair EW, van der Heijde DMFM, Smolen JS, et al. Combination of infliximab and methotrexate therapy for early rheumatoid arthritis: a randomized, controlled trial (ASPIRE). Arthritis Rheum. 2004;50(11):3432-3443. doi:10.1002/art.20568Demonstrated superiority of infliximab + MTX over MTX alone in early RA for clinical, radiographic, and functional outcomes.
- Westhovens R, Yocum D, Han J, et al. The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities: a large, randomized, placebo-controlled trial (START). Arthritis Rheum. 2006;54(4):1075-1086. doi:10.1002/art.21734Large safety trial (>1,000 patients) assessing infliximab in RA patients with comorbidities including prior malignancy.
- Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res. 2021;73(7):924-939. doi:10.1002/acr.24596Current ACR guideline positioning TNF inhibitors as preferred biologics after csDMARD failure in RA.
- Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological DMARDs: 2022 update. Ann Rheum Dis. 2023;82(1):3-18. doi:10.1136/ard-2022-223356EULAR consensus on biologic DMARD sequencing and monitoring in RA.
- Tracey D, Klareskog L, Sasso EH, et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117(2):244-279. doi:10.1016/j.pharmthera.2007.10.001Comprehensive review of TNF-α biology and mechanisms of anti-TNF agents including infliximab.
- Klotz U, Teml A, Schwab M. Clinical pharmacokinetics and use of infliximab. Clin Pharmacokinet. 2007;46(8):645-660. doi:10.2165/00003088-200746080-00002Key PK review providing Vd, clearance, half-life estimates across indications and influence of MTX co-medication.
- Fasanmade AA, Adedokun OJ, Olson A, et al. Population pharmacokinetic analysis of infliximab in patients with ulcerative colitis. Eur J Clin Pharmacol. 2009;65(12):1211-1228. doi:10.1007/s00228-009-0718-4Population PK model identifying body weight, ATI status, and albumin as key covariates for infliximab clearance.
- Infliximab. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024. NCBI BookshelfPeer-reviewed clinical pharmacology overview covering all approved indications, dosing, adverse effects, and monitoring.
- Brandse JF, Mould D, Smeekes O, et al. A real-life population pharmacokinetic study reveals factors associated with clearance and immunogenicity of infliximab in inflammatory bowel disease. Inflamm Bowel Dis. 2017;23(4):650-660. doi:10.1097/MIB.0000000000001043Real-world pop PK study identifying body weight, albumin, and anti-drug antibodies as key determinants of infliximab clearance in IBD.