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Steroids for an immunotherapy side effect are reduced slowly, usually over at least 4 to 6 weeks, because stopping too fast can bring it back. A month or more of higher-dose steroids weakens defences against Pneumocystis pneumonia, so a preventive antibiotic (usually co-trimoxazole) is often given. Your body's own steroid production may need checking before the last tablets stop.
Steroids are the first-line treatment for most irAEs, and their own harms (hyperglycaemia, mood change, insomnia, gastritis, weight gain, osteoporosis and opportunistic infection including Pneumocystis pneumonia) need counselling (SITC 2021, LE: 1). ASCO 2021 (abstract): taper over at least 4 to 6 weeks. SITC tapers over 4 to 6 weeks for hepatitis, pneumonitis and myocarditis, but within 4 weeks for colitis (LE: 1).
Pneumocystis prophylaxis: ASCO/IDSA 2018 recommends it for regimens carrying more than 3.5% risk, for example 20 mg prednisone equivalent or more daily for a month or longer. ECIL-5 (haematological patients) lists more than 4 weeks of corticosteroids as a main indication and makes trimethoprim/sulfamethoxazole the drug of choice, with pentamidine, atovaquone and dapsone second-line.
Adrenal axis: doses equivalent to 7.5 mg prednisolone or more for over 3 weeks can suppress the adrenal glands, so ESE 2022 advises at least a morning cortisol (with ACTH, and a Synacthen test if needed) before stopping. The 2024 ESE/Endocrine Society guideline on glucocorticoid-induced adrenal insufficiency tapers faster in the supraphysiological range and more slowly at physiological doses.
Why: Knowing what to look for lets the patient report problems early.
“When beginning corticosteroid therapy, patients should be specifically counseled about potential toxicities, including hyperglycemia, mood disturbances, insomnia, gastritis, weight gain, and opportunistic infections (eg, Pneumocystis pneumonia)”
Why: Reducing too quickly can make the inflammation come back.
“Corticosteroids should be tapered over the course of at least 4-6 weeks.”
Why: At this dose and duration the risk of a serious Pneumocystis lung infection is high enough to justify prevention.
“Pneumocystis jirovecii prophylaxis is recommended for patients receiving chemotherapy regimens that are associated with a > 3.5% risk for pneumonia as a result of this organism (eg, those with ≥ 20 mg prednisone equivalents daily for ≥ 1 month or on the basis of purine analog usage).”
ASCO and Infectious Diseases Society of America, Journal of Clinical Oncology 2018
Why: Co-trimoxazole is the most effective preventive; the others are alternatives for allergy or intolerance.
“All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated.”
European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy 2016
Why: Withdrawal symptoms and adrenal insufficiency mostly appear at the low end of the taper.
“In general, tapering of glucocorticoids can be more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing.”
European Society of Endocrinology and Endocrine Society, European Journal of Endocrinology 2024
Why: Long steroid courses can switch off the adrenal glands, and stopping suddenly can cause an adrenal crisis.
“Use of doses equivalent to 7.5 mg prednisolone or higher for more than 3 weeks can lead to secondary adrenal insufficiency. Thus, at least a medication fasting morning cortisol (plus ACTH) and if needed a 250 µg Synacthen® test should be considered if glucocorticoids are considered to be stopped.”
European Society of Endocrinology, European Journal of Endocrinology 2022
Why: Prolonged high-dose steroids add harm without benefit when the toxicity is steroid-refractory.
“However, in patients who do not respond to initial corticosteroid therapy, second-line immunosuppressive therapy should be considered.”
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
On the taper, ASCO 2021 (abstract) sets at least 4 to 6 weeks and SITC 2021 agrees for most organs (LE: 1 for hepatitis) but tapers colitis within 4 weeks (LE: 1). On Pneumocystis, the ASCO/IDSA 2018 threshold (20 mg prednisone equivalent or more daily for 1 month or more) is the guideline written for adults with cancer in general and is the clearest trigger; ECIL-5 uses more than 4 weeks of corticosteroids in haematological patients and makes co-trimoxazole the drug of choice (graded A-II for adults in its abstract). SITC 2021 names Pneumocystis among the risks to counsel about but sets no prophylaxis threshold in the text read. On the adrenal axis, ESE 2022 advises a morning cortisol before stopping after more than 3 weeks at 7.5 mg prednisolone or more, and the 2024 ESE/Endocrine Society guideline tapers more slowly at physiological doses. None of these is a trial in checkpoint inhibitor patients.
ASCO, Journal of Clinical Oncology 2021 · SITC, Journal for ImmunoTherapy of Cancer 2021 · ASCO and Infectious Diseases Society of America, Journal of Clinical Oncology 2018 · European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy 2016 · European Society of Endocrinology, European Journal of Endocrinology 2022 · European Society of Endocrinology and Endocrine Society, European Journal of Endocrinology 2024
Where it differs: Tapers corticosteroids within 4 weeks after colitis improves to grade 1 or less, instead of over 4 to 6 weeks as for hepatitis and pneumonitis.
Evidence: LE: 1.
Where it differs: Uses duration (more than 4 weeks) rather than a dose threshold, and gives co-trimoxazole 2 to 3 times weekly for the whole period at risk.
Evidence: IDSA grading; co-trimoxazole as drug of choice in adults graded A-II.
European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy 2016
Where it differs: For rheumatic irAEs, tapers to the lowest effective dose that controls symptoms rather than to zero over a fixed period, with a conventional DMARD above 10 mg/day prednisone.
Evidence: LoE 4; level of agreement 9.4 out of 10.
European Alliance of Associations for Rheumatology (EULAR), Annals of the Rheumatic Diseases 2021
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Counsel about steroid toxicities, including Pneumocystis pneumonia | LE: 1 | SITC, Journal for ImmunoTherapy of Cancer 2021 |
| Taper over at least 4 to 6 weeks | expert consensus | ASCO, Journal of Clinical Oncology 2021 |
| Taper within 4 weeks after colitis improves to grade 1 or less “Corticosteroids should be tapered within 4 weeks after improvement of diarrhea or colitis symptoms to grade ≤1” | LE: 1 | SITC, Journal for ImmunoTherapy of Cancer 2021 |
| Co-trimoxazole 2 to 3 times weekly as the drug of choice for Pneumocystis prophylaxis in adults “Trimethoprim/sulfamethoxazole given 2-3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults” | A-II | European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy 2016 |
| More than 4 weeks of corticosteroids as a main indication for prophylaxis “The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children.” | not graded in the abstract | European Conference on Infections in Leukaemia (ECIL-5), Journal of Antimicrobial Chemotherapy 2016 |
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