First-Line Treatment for Pneumocystis jirovecii Pneumonia (PJP)

Standard Treatment Regimen

• The American College of Oncology recommends high-dose trimethoprim-sulfamethoxazole (TMP-SMX) as the first-line treatment for PJP, dosed at 15-20 mg/kg/day of the trimethoprim component, divided into doses every 6-8 hours for 14-21 days, across all patient populations, including those with HIV, hematologic malignancies, solid organ transplants, and other immunocompromised states 1, 2

First-Line Alternative Regimens

• The American College of Oncology recommends clindamycin (600-900 mg IV every 6-8 hours or 300-450 mg PO every 6 hours) plus primaquine (15-30 mg base PO daily) as the preferred alternative when TMP-SMX cannot be used due to allergy, intolerance, or treatment failure 1, 3
• Clindamycin plus primaquine is superior to pentamidine for both efficacy and safety 3
• Clindamycin plus primaquine requires G6PD testing before initiation due to risk of hemolytic anemia in G6PD-deficient patients 1, 3

Adjunctive Corticosteroid Therapy

• The American College of Oncology recommends adjunctive corticosteroids for patients with severe PJP (PaO₂ <70 mmHg or A-a gradient >35 mmHg on room air), which reduces mortality in HIV-infected patients, but notes that in non-HIV immunocompromised patients, adjunctive corticosteroids are not generally recommended and should only be considered on an individual basis for critical respiratory insufficiency 1

Treatment Duration and Monitoring

• The American College of Oncology recommends treatment duration of 14-21 days depending on clinical response for non-HIV patients 1
• If no response after 7 days, reassess with repeat imaging and consider bronchoscopy 1

Secondary Prophylaxis

• The American College of Oncology recommends secondary prophylaxis to prevent recurrence in all patients who have been successfully treated for PJP, with options including TMP-SMX, monthly aerosolized pentamidine, dapsone, and atovaquone 1, 2, 3

Common Pitfalls to Avoid

• The American College of Oncology recommends against delaying treatment while awaiting bronchoscopy if PJP is suspected based on clinical presentation and elevated LDH 1
• The American College of Rheumatology recommends considering drug interactions when using TMP-SMX with methotrexate, as this combination increases risk of severe cytopenia 4
• The American College of Oncology recommends always checking G6PD levels before using primaquine or dapsone to prevent life-threatening hemolysis 1, 3

Treatment of Pneumocystis jirovecii Pneumonia with Hypoxemia

Standard Treatment Regimen

• The American Thoracic Society recommends high-dose trimethoprim-sulfamethoxazole (TMP-SMX) at 15-20 mg/kg/day of the trimethoprim component divided every 6-8 hours for 14-21 days for the treatment of PCP with hypoxemia, with adjunctive corticosteroids added when PaO₂ is <70 mmHg on room air or alveolar-arterial gradient is >35 mmHg 5, 6

Adjunctive Corticosteroid Therapy for Hypoxemia

• The Infectious Diseases Society of America recommends adding prednisolone 40 mg twice daily for 5 days, followed by 40 mg once daily for 5 days, then 20 mg once daily for 11 days in patients with severe PCP defined by hypoxemia (PaO₂ <70 mmHg on room air or A-a gradient >35 mmHg) 5
• The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend corticosteroids alongside high-dose IV TMP-SMX and reduction in immunosuppressive medications for kidney transplant recipients with moderate to severe PCP (PaO₂ <70 mmHg or A-a gradient >35 mmHg) 6

Emerging Evidence on Lower-Dose TMP-SMX

• The current guideline evidence still recommends standard high-dose therapy, particularly for severe disease with hypoxemia, although recent research suggests potential benefits of lower dosing 5, 6

Treatment of Pneumocystis jirovecii Pneumonia (PJP)

Treatment Monitoring and Response Assessment

• The European Society for Medical Oncology recommends evaluating patients daily for clinical improvement, and not ordering repeat imaging earlier than 7 days after treatment initiation, with treatment failure criteria including persistent fever, progressive or new infiltrates, and rising inflammatory markers after 7 days 7
• The European Society for Medical Oncology suggests that bronchoscopy timing is critical, as BAL remains positive for P. jirovecii for several days despite appropriate therapy, so repeat bronchoscopy can confirm diagnosis even after treatment initiation 7

Critical Clinical Pitfalls to Avoid

• The European Society for Medical Oncology advises against delaying treatment while awaiting bronchoscopy if PJP is suspected based on clinical presentation, CT findings suggestive of PJP, and elevated lactate dehydrogenase, and recommends starting high-dose TMP-SMX before bronchoscopy 7

Secondary Prophylaxis

• The European Society for Medical Oncology recommends that all patients successfully treated for PJP require secondary prophylaxis to prevent recurrence, with preferred agents including intermittent TMP-SMX or monthly aerosolized pentamidine 7
• The British Society of Gastroenterology suggests alternative agents for secondary prophylaxis, including dapsone 100 mg daily or atovaquone 1500 mg daily for sulfa-allergic patients 8

Special Populations

• The European League Against Rheumatism recommends PJP prophylaxis for patients on triple immunosuppression, with a prophylaxis regimen of TMP-SMX 800/160 mg three times weekly 9
• The British Society of Gastroenterology advises PJP prophylaxis for high-risk scenarios, including corticosteroids >2 weeks plus cyclophosphamide, or corticosteroids plus thiopurine plus calcineurin inhibitor/infliximab 8
• The European Society for Medical Oncology recommends PJP prophylaxis for all patients receiving teclistamab or elranatamab due to a 3.6-4.9% incidence in clinical trials 10
• The European Society for Medical Oncology suggests considering PJP prophylaxis with TMP-SMX for brain metastases patients on steroids >few weeks plus additional immunosuppressive systemic therapy 11

Treatment of PJP Pneumonia with Hypoxia in Chronic Steroid Users

Critical Management Considerations for Chronic Steroid Users

• The European Association of Neuro-Oncology and European Society for Medical Oncology guidelines suggest that patients on chronic steroids are at high risk for PJP and require additional corticosteroids as adjunctive therapy for severe PJP, which serves a different purpose than the baseline immunosuppressive steroids, in patients with hypoxia (PaO₂ <70 mmHg or A-a gradient >35 mmHg) 12, 13
• The Annals of Oncology recommends that patients on chronic steroids should not have their baseline steroids abruptly discontinued during PJP treatment, as this can precipitate adrenal crisis, and the adjunctive corticosteroid regimen for PJP should be given in addition to their baseline steroid requirement 12

Secondary Prophylaxis After Successful Treatment

• The Annals of Oncology guidelines recommend that any patient requiring >20 mg prednisone (or equivalent) daily for >4 weeks should receive PJP prophylaxis with TMP-SMX, which provides a 91% reduction in PJP occurrence, and the European Association of Neuro-Oncology and European Society for Medical Oncology guidelines specifically recommend PJP prophylaxis with trimethoprim-sulfamethoxazole for brain tumor patients requiring steroid treatment >4 weeks 12

Pneumocystis jirovecii Pneumonia Treatment and Prophylaxis

Special Populations Requiring Prophylaxis

• The Centers for Disease Control and Prevention recommends initiating prophylaxis in HIV-infected patients with CD4+ counts <200 cells/μL or <20% of total T-lymphocytes 14
• The National Comprehensive Cancer Network recommends that allogeneic stem cell transplant recipients receive prophylaxis for at least 6 months and while receiving immunosuppressive therapy, and patients receiving alemtuzumab require prophylaxis for a minimum of 2 months after treatment and until CD4 count is >200 cells/μL 15
• The National Comprehensive Cancer Network also recommends that patients receiving temozolomide with radiation therapy require prophylaxis during concurrent treatment and until recovery from lymphocytopenia 15

Treatment of Pneumocystis jirovecii Pneumonia (PJP)

Secondary Prophylaxis

• The American Association for the Study of Liver Diseases recommends continuing secondary prophylaxis for at least 6-12 months post-transplant in solid organ transplant recipients 16
• Secondary prophylaxis should be continued while immunosuppression persists in other populations, with options including TMP-SMX, dapsone, atovaquone, and monthly aerosolized pentamidine, although specific recommendations may vary by guideline society 16

Treatment of Pneumocystis jirovecii Pneumonia (PJP)

Management of Immunosuppressive Therapy During Treatment

• The American Society of Hematology recommends temporarily discontinuing bispecific antibody therapy during active PJP treatment until symptom resolution 17, 18, 19

Secondary Prophylaxis

• The Infectious Diseases Society of America recommends TMP-SMX 800/160 mg (double-strength) three times weekly for secondary prophylaxis, providing 91% reduction in PJP occurrence and 83% reduction in PJP-related mortality 18
• The American Society of Transplantation recommends continuing secondary prophylaxis for at least 6-12 months post-transplant in solid organ transplant recipients, and while immunosuppression persists in other populations 18

Pneumocystis Jirovecii Pneumonia Prevention and Treatment

Pathophysiology and Risk

• P. jirovecii is a unicellular fungal organism that colonizes the respiratory tract of healthy individuals, but causes severe pneumonia when cell-mediated immunity is impaired, particularly in patients with compromised T-cell function 20
• The infection progresses from minor illness to severe inflammatory pneumonia with respiratory failure, particularly in patients with compromised T-cell function 20

High-Risk Populations Requiring Prophylaxis

• Acute lymphoblastic leukemia (ALL) patients throughout anti-leukemic therapy are at high risk for PJP, according to the National Comprehensive Cancer Network (NCCN) 21
• Allogeneic stem cell transplant recipients are at high risk for PJP for at least 6 months post-transplant and while receiving immunosuppressive therapy, as recommended by the NCCN 21
• Patients receiving bispecific antibodies, such as teclistamab or elranatamab, are at high risk for PJP due to a 3.6-4.9% incidence in trials, as reported in the Blood Cancer Journal 22
• Patients on prolonged corticosteroids, receiving ≥20 mg prednisone daily (or equivalent) for ≥4 weeks, are at high risk for PJP, according to the NCCN 21
• Patients receiving specific immunosuppressive agents, including alemtuzumab, purine analogs, and T-cell depleting agents, are at high risk for PJP, as recommended by the NCCN 21

Prophylaxis Regimens

• Atovaquone 1500 mg daily is an alternative prophylaxis option for TMP-SMX intolerant patients, as recommended by the NCCN 21
• Dapsone 100 mg daily is an alternative prophylaxis option for TMP-SMX intolerant patients, but requires G6PD testing, as recommended by the NCCN 21
• Aerosolized pentamidine 300 mg monthly is an alternative prophylaxis option for TMP-SMX intolerant patients, as recommended by the NCCN 21

PJP Pneumonia Treatment in Sulfa-Allergic Patients

Secondary Prophylaxis

• The Centers for Disease Control and Prevention recommends atovaquone 1,500 mg PO daily as a preferred oral option for secondary prophylaxis in sulfa-allergic patients 23
• The Centers for Disease Control and Prevention recommends dapsone 100 mg PO daily as an option for secondary prophylaxis in sulfa-allergic patients, requiring G6PD testing 23
• The Centers for Disease Control and Prevention recommends aerosolized pentamidine 300 mg monthly as an option for secondary prophylaxis in sulfa-allergic patients 23
• Secondary prophylaxis should continue for at least 6-12 months post-transplant in solid organ recipients, and indefinitely while immunosuppression persists in other populations 23
• In HIV patients, secondary prophylaxis should continue until CD4 count >200 cells/μL for at least 3 months 23

Treatment of PCP Pneumonia

First-Line Alternative Regimens

• The Centers for Disease Control and Prevention recommends pentamidine isethionate as a second-line alternative for patients intolerant of TMP-SMX or demonstrating clinical treatment failure after 5-7 days, with dosing at 4 mg/kg/day once daily administered intravenously over 60-90 minutes for 21 days 24
• The Centers for Disease Control and Prevention suggests that after 7-10 days of clinical improvement with IV pentamidine, consider switching to oral atovaquone to complete the 21-day course 24
• The Centers for Disease Control and Prevention advises against combining pentamidine with TMP-SMX, as there is no evidence for synergistic effects and potential for increased toxicity 24
• The Centers for Disease Control and Prevention recommends trimethoprim-dapsone as an alternative oral regimen, with dosing at trimethoprim 20 mg/kg/day plus dapsone 100 mg daily for 21 days 24

Monitoring and Treatment Adjustments

• The Centers for Disease Control and Prevention recommends that if no clinical improvement is seen within 5-8 days, consider switching to an alternative agent 24
• The Centers for Disease Control and Prevention warns of pentamidine-specific toxicities, including renal toxicity, severe hypotension, prolonged QT interval, cardiac arrhythmias, and hypoglycemia 24

Adjunctive Corticosteroid Therapy

• The National Kidney Foundation recommends that for severe PCP with hypoxemia, add corticosteroids regardless of which anti-PCP agent is used 25

Critical Pitfalls to Avoid

• The Centers for Disease Control and Prevention advises against using pentamidine and TMP-SMX together due to increased toxicity without added benefit 24

Secondary Prophylaxis for Pneumocystis jirovecii Pneumonia (PCD Guideline)

Indication for Lifelong Prophylaxis

• All patients who have been successfully treated for PCP should receive lifelong secondary prophylaxis to prevent recurrence. 26

Alternative Prophylactic Regimens (TMP‑SMX‑Intolerant Patients)

• Aerosolized pentamidine 300 mg administered monthly via a Respirgard II nebulizer is recommended as an alternative prophylaxis option when TMP‑SMX cannot be used. 26

Special Populations Requiring Continuous Prophylaxis

• Individuals with a prior episode of PCP must continue prophylaxis indefinitely, irrespective of CD4 count or clinical status. 26

TMP‑SMX Prophylaxis for Pneumocystis jirovecii in Immunocompromised Patients During Sepsis Treatment

Guideline Recommendations and Indications

• The EULAR (European Alliance of Associations for Rheumatology) guideline recommends trimethoprim‑sulfamethoxazole (TMP‑SMX) prophylaxis for patients receiving rituximab, cyclophosphamide, and/or high‑dose glucocorticoids to prevent Pneumocystis jirovecii pneumonia (PJP) and other opportunistic infections【27】.
• The ASCO/IDSA (American Society of Clinical Oncology / Infectious Diseases Society of America) guideline advises TMP‑SMX prophylaxis for cancer‑related immunosuppression when patients are at risk for prolonged neutropenia or are receiving ≥20 mg prednisone equivalents daily for ≥1 month【28】.

Rationale for Continuing TMP‑SMX While Treating Sepsis

• Prophylactic TMP‑SMX specifically targets Pneumocystis jirovecii, a critical threat in immunocompromised patients, and its protective role remains essential even when the patient is concurrently receiving vancomycin and piperacillin‑tazobactam (Zosyn) for bacterial sepsis【27】【28】.

Avoiding Premature Discontinuation

• Broad‑spectrum antibiotics used for sepsis (e.g., vancomycin, Zosyn) do not provide coverage for PJP; therefore, discontinuing TMP‑SMX solely because multiple antibiotics are being administered can increase the risk of PJP【27】【28】.
• The prophylactic dose of TMP‑SMX serves a distinct immunologic purpose and should be maintained unless specific adverse effects (e.g., severe hyperkalemia, pancytopenia, acute kidney injury) develop【27】【28】.

Renal Dosing Adjustments and Secondary Prophylaxis for Pneumocystis jirovecii Pneumonia

Treatment Dosing Adjustments in Renal Impairment

• In patients with creatinine clearance 10–30 mL/min, trimethoprim‑sulfamethoxazole should be reduced to 5 mg/kg of the trimethoprim component every 12 hours; for creatinine clearance < 10 mL/min, the dose should be given once every 24 hours. 29

Secondary Prophylaxis Regimens and Dosing

• The preferred secondary prophylaxis regimen is trimethoprim‑sulfamethoxazole double‑strength (800/160 mg) taken three times weekly, which provides an approximate 91 % reduction in PJP incidence and an 83 % reduction in PJP‑related mortality. 29

• For patients with renal impairment creatinine clearance 15–30 mL/min, the prophylactic trimethoprim‑sulfamethoxazole dose should be halved; for creatinine clearance < 15 mL/min, either the half‑dose may be continued or an alternative prophylactic agent should be used. 29

Guideline Recommendations for Timing of Rituximab Resumption After Pneumocystis jirovecii Pneumonia

Assessment of Treatment Response

• The European Society for Medical Oncology (ESMO) recommends that imaging studies to reassess response to high‑dose trimethoprim‑sulfamethoxazole should not be ordered earlier than 7 days after therapy initiation because earlier imaging does not reliably reflect treatment efficacy. 30
• According to ESMO, clinical status should be evaluated daily, but definitive radiologic response cannot be confirmed before day 7 of antimicrobial therapy. 30
• ESMO notes that bronchoalveolar lavage (BAL) specimens often remain positive for P. jirovecii for several days despite appropriate treatment, making early microbiologic testing an unreliable indicator of cure. 30
• Persistent fever, worsening infiltrates on imaging, or rising inflammatory markers after 7 days of therapy are typical signs of treatment failure and should prompt consideration of alternative antimicrobial regimens, per ESMO guidance. 30

Criteria for Safely Resuming Rituximab

• The ESMO guideline states that rituximab may be restarted only after chest imaging has normalized or shown significant improvement, indicating adequate resolution of pulmonary involvement. 30

All facts are derived from the European Society for Medical Oncology recommendations published in Annals of Oncology (2015) 30.

TMP‑SMX as the Preferred Agent for Pneumocystis jirovecii Pneumonia

1. Superior Efficacy and Cost‑Effectiveness

• The Centers for Disease Control and Prevention (CDC) recommends trimethoprim‑sulfamethoxazole (TMP‑SMX) as the first‑line agent for both primary and secondary prophylaxis of PCP because it provides greater overall efficacy and lower drug acquisition cost than aerosolized pentamidine when patients can tolerate oral therapy. 31
• In the ACTG 021 trial, initiating secondary prophylaxis with TMP‑SMX yielded higher prophylactic success rates than alternative regimens, even among patients with advanced immunosuppression who often cannot tolerate prolonged therapy. 31
• TMP‑SMX delivers systemic antimicrobial activity against Pneumocystis spp., whereas aerosolized pentamidine achieves only local pulmonary concentrations and may miss extrapulmonary infection. 32

2. Proven Efficacy Across Diverse Patient Populations

• In immunosuppressed pediatric oncology patients, a regimen of TMP‑SMX (150 mg/m² trimethoprim + 750 mg/m² sulfamethoxazole) administered three consecutive days per week prevented all cases of PCP, compared with a 21 % incidence in placebo‑treated children. 32
• Among adults with Kaposi’s sarcoma, none of the 30 patients receiving TMP‑SMX prophylaxis developed PCP, whereas 16 of 30 untreated patients did. 32
• The CDC recommends TMP‑SMX as first‑line prophylaxis for children aged ≥6 years, mirroring adult recommendations because of its favorable safety profile, proven efficacy, and ease of administration relative to aerosolized agents. [33][34]

3. Recommended Prophylaxis Regimens

3.1 Adults (Primary & Secondary Prophylaxis)

• One double‑strength tablet (800 mg sulfamethoxazole / 160 mg trimethoprim) taken once daily, seven days per week. 31

3.2 Children (Prophylaxis)

• Trimethoprim 150 mg/m² plus sulfamethoxazole 750 mg/m² divided twice daily on three non‑consecutive days per week (e.g., Monday‑Tuesday‑Wednesday), with a maximum daily dose not exceeding 320 mg trimethoprim and 1 600 mg sulfamethoxazole. [33][35]

4. Alternative Therapies When TMP‑SMX Is Contra‑Indicated

• Aerosolized pentamidine (300 mg once monthly via nebulizer) is listed as a second‑line prophylactic option. 31
• Dapsone (100 mg daily for prophylaxis; 100 mg daily combined with trimethoprim 20 mg/kg/day for treatment) may be used after confirming normal glucose‑6‑phosphate dehydrogenase (G6PD) activity. 35

5. Management of TMP‑SMX Intolerance

• Mild hypersensitivity reactions (e.g., rash, pruritus) do not preclude continued use; breakthrough PCP rates were similar in patients with prior mild intolerance versus those without (32 % vs 26 %). 36
• Desensitization protocols can enable some patients with previous adverse reactions to tolerate TMP‑SMX, although clinicians remain cautious about severe hypersensitivity. 36
• Life‑threatening reactions (anaphylaxis, Stevens‑Johnson syndrome, severe hypotension) mandate permanent discontinuation of TMP‑SMX. 35
• For moderate reactions (e.g., rash, neutropenia), a temporary discontinuation with re‑challenge after ≤2 weeks is advised. 35

6. Monitoring and Pitfalls

• Monthly complete blood count monitoring is recommended during TMP‑SMX prophylaxis to detect hematologic toxicity such as neutropenia or thrombocytopenia. 35
• Discontinuing TMP‑SMX prophylaxis in patients receiving broad‑spectrum antibiotics for sepsis is discouraged, as these agents do not provide PCP coverage and cessation increases infection risk. (Citation not required; excluded per instructions.)
• Breakthrough PCP while on TMP‑SMX is more often attributable to poor adherence or gastrointestinal malabsorption rather than antimicrobial resistance. [33][34]
• After breakthrough PCP, TMP‑SMX remains the preferred therapeutic agent provided the patient can tolerate, reliably ingest, and absorb the medication. [33][34][36][37]
• Aerosolized pentamidine should be avoided in individuals with a history of hypoglycemia, pancreatitis, arrhythmia, or severe hypotension related to pentamidine exposure. 36
• Pre‑treatment with inhaled β₂‑agonists (e.g., two puffs of albuterol 100 µg each, 10 minutes before administration) mitigates bronchospastic side effects of aerosolized pentamidine. [31][36]

Prophylaxis Regimens and Contraindications for PCP in Penicillin‑Allergic Immunocompromised Patients

First‑Line Prophylaxis Dose (TMP‑SMX)

• In immunocompromised patients who have a penicillin allergy, the CDC MMWR Recommendations advise using trimethoprim‑sulfamethoxazole 800 mg/160 mg (double‑strength) either three times weekly or one tablet daily as the standard prophylactic regimen for Pneumocystis jirovecii pneumonia (PCP)【38, 39】.

True Contraindications to TMP‑SMX

• A documented history of Stevens‑Johnson syndrome or a severe exfoliative rash triggered by sulfonamide drugs is considered a definite contraindication to TMP‑SMX prophylaxis in this population【38】.

Aerosolized Pentamidine Regimen

• When TMP‑SMX cannot be used, the CDC MMWR Recommendations permit inhaled pentamidine 300 mg administered once monthly via a Respirgard II or Fisoneb nebulizer to provide pulmonary PCP prophylaxis【38, 39】.

Contraindications to Aerosolized Pentamidine

• Patients with a prior episode of pentamidine‑related hypoglycemia, pancreatitis, cardiac arrhythmia, or severe hypotension should avoid aerosolized pentamidine because of the risk of recurrence【38, 39】.

Bronchospasm Prevention Prior to Pentamidine Inhalation

• Administration of two puffs of albuterol (100 µg each) before the inhaled pentamidine dose markedly reduces the incidence of bronchospasm associated with the procedure【38, 39】.

Trimethoprim‑Sulfamethoxazole Prophylaxis for Pneumocystis jirovecii Pneumonia in Interstitial Lung Disease

Indications for Prophylaxis

• In patients with interstitial lung disease who receive ≥20 mg prednisone (or equivalent) daily for ≥4 weeks, prophylaxis against PCP is recommended. Strength: moderate recommendation (NCCN). 40
• When corticosteroids are combined with any of the following agents—cyclophosphamide, rituximab, mycophenolate mofetil, azathioprine, or tocilizumab— prophylaxis is indicated regardless of steroid dose. Strength: strong recommendation (Rheumatology guideline). 41

Preferred Prophylactic Regimen

• Trimethoprim‑sulfamethoxazole (TMP‑SMX) double‑strength (800 mg/160 mg) administered three times weekly (consecutive or non‑consecutive days) is the preferred regimen for PCP prophylaxis in this population. Strength: strong recommendation (Rheumatology guideline). 41

Alternative Agents for TMP‑SMX Intolerance

• Dapsone 100 mg orally once daily may be used when TMP‑SMX cannot be tolerated; G6PD deficiency must be screened before initiation. Strength: moderate recommendation (allergy/immunology guideline). 42

Duration of Prophylaxis

• Continue prophylaxis for the entire period of high‑dose corticosteroid therapy (≥20 mg prednisone daily). 40
• Maintain prophylaxis while any cytotoxic or biologic immunosuppressive agent is being administered. 41

Monitoring and Safety Considerations

• Avoid concurrent use of treatment‑dose methotrexate with TMP‑SMX because of a high risk of severe bone‑marrow suppression. Strength: moderate recommendation (NCCN). 40
• Screen for latent tuberculosis before initiating rituximab or cyclophosphamide. Strength: moderate recommendation (NCCN). 40
• Test for hepatitis B and C prior to starting anti‑TNF therapy. Strength: moderate recommendation (NCCN). 40