ICI-associated myositis
Also called: inflammatory myopathy · ICI myositis · immune-related myositis · checkpoint inhibitor myopathy
Around 1% on anti-PD-(L)1, and the member of the myositis/myocarditis/myasthenia triad most likely to present first — 9% of cases carry myocarditis and 9% myasthenia gravis. CK cuts both ways: some patients are asymptomatic with a raised CK, others symptomatic with a normal one, so neither result closes the question.
Reported frequency
1% — Myositis in patients treated with anti-PD-(L)1 ICIs
of Not stated in the chapter · SITC's chapter statement, given without a cohort or denominator. Carried because it is the only frequency figure any source held here reports for this entity, and its denominator field says what is missing
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Severity and class
1% anti-PD-(L)1 vs <1% anti-CTLA-4 — Myositis frequency by ICI class
of Not stated — SITC gives the two class figures without numerators or cohort sizes · SITC's chapter statement. The chapter adds that little systematic data exist for other ICIs, so this comparison covers two classes and not the field
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Onset
No source cited here reports an onset window for ICI myositis. The neurological median of 29 days belongs to myasthenia gravis in a different study and is not carried across, even though the two co-occur. The bucket does not narrow a statement no source made.
Presentation
- · Muscle weakness in the limbs, and myalgia
- · Restricted eye movement
- · Problems with speaking or swallowing
- · Asymptomatic with an elevated CK — SITC names this as a presentation, so a raised CK on a routine panel is a finding, not noise
- · Symptomatic with a NORMAL CK — the converse SITC also names, and the reason a normal CK does not exclude myositis
Differential
- · Myasthenia gravis, which SITC separates electrodiagnostically and which carries 9% of myositis cases — fatigable weakness with ptosis and diplopia points there
- · Myocarditis, present in 9% of myositis cases and the reason cardiac testing belongs in this work-up rather than in the follow-up
- · Statin and other drug-induced myopathy
- · Hypothyroidism, itself an ICI toxicity, and other metabolic causes of a raised CK
- · Malignant infiltration, deconditioning and cachexia
Work-up
Rheumatology or neurology consultation · All patients
SITC attaches it to POSSIBLE myositis, before the diagnosis is established, and again at grade 3.
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Creatine kinase · All patients
The central test and the one most likely to mislead. SITC states both failure modes explicitly: asymptomatic patients with raised CK, and symptomatic patients with normal CK. Its trajectory also gates the 4-6 week escalation decision.
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Monitoring for signs of myocarditis · All patients
SITC requires it in every possible myositis. This is the finding that converts the ICI decision from hold to permanent discontinuation, and myocarditis is the member of the triad with 50% reported fatality.
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Monitoring for signs of myasthenia gravis · All patients
The third member of the triad, present in 9% of myositis cases; SITC evaluates all three together.
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Assessment of respiratory and diaphragmatic muscle involvement · All patients
SITC names diaphragmatic or respiratory muscle involvement as a direct mechanism of death from myositis itself, separate from the myocarditis route.
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Assessment for dysphagia · All patients
Difficulty swallowing is both a presenting symptom and, at grade 3, one of the three findings that triggers IV methylprednisolone with plasmapheresis or IVIG.
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Grade ladder
Grade 1
Continue the ICIOutpatientGrade 1 — and the rung with a trap in it. ASCO's cross-organ default continues an ICPi at grade 1 and its exceptions are neurologic, hematologic and cardiac, not musculoskeletal, so on its face it applies here. SITC overrides it conditionally: grade 1 myositis presenting with an elevated CK AND muscle weakness should be managed as grade 2. A grade 1 myositis with both findings is therefore not a grade 1 decision.
Dose not carried
SITC offers oral corticosteroids at this level and states no dose, route, taper or duration for them — the chapter's only myositis dose is the grade 3 prednisone 1 mg/kg. The rung records that a steroid may be offered without a dose being carried, rather than importing the grade 3 figure downward.
- · Analgesia with acetaminophen or NSAIDs if no contraindications are present
- · Rheumatology or neurology consultation — SITC attaches it to possible myositis, not to a grade
- · Monitor for myocarditis and myasthenia gravis from the first presentation
Escalate when: An elevated CK together with muscle weakness — SITC's explicit instruction is to manage that combination as grade 2, so it is the trigger rather than a reason to watch. Any cardiac or myasthenic sign escalates independently.
Grade 2
Hold the ICIOutpatientGrade 2 — ASCO may suspend the ICPi for most grade 2 toxicities, with consideration of resuming when symptoms revert to grade 1 or lower. This rung also receives the grade 1 cases that carry both an elevated CK and muscle weakness.
Dose not carried
Same as grade 1: oral corticosteroids are offered without a stated dose. SITC's 1 mg/kg prednisone figure is written for grade 3 and is not pulled down to this rung.
- · Analgesia with acetaminophen or NSAIDs if no contraindications are present
- · Serial CK, since its trajectory gates the later escalation decision
- · Continue monitoring for myocarditis and myasthenia gravis
Escalate when: Weakness severely limiting mobility, dysphagia, or any cardiac or respiratory involvement. A rising CK on treatment.
Grade 3
Hold — consider permanent discontinuationConsider admissionGrade 3 — the rung where SITC becomes specific. Refer to rheumatology or neurology, consider hospitalisation for severe weakness, hold the ICI until myositis is grade ≤1 while OFF immune suppression, and permanently discontinue if there is any evidence of myocardial involvement. That last clause is the reason the cardiac assessment is part of the work-up rather than a later question.
Corticosteroid 1 mg/kg/day (oral)
Pulse: Methylprednisolone IV 1–2 mg/kg, or a higher-dose bolus — SITC scopes this to grade 3 myositis WITH muscle weakness severely limiting mobility, cardiac or respiratory involvement, or dysphagia — not to every grade 3. Plasmapheresis or IVIG may be considered alongside it.
Taper within 6 weeks or longer, starting once: Not stated for this entity. SITC gives the starting dose and no taper; the ceiling shown is ASCO's cross-organ 'at least 4-6 weeks', a FLOOR in its own text, rendered open-ended rather than as a completion date. Do not confuse it with SITC's separate 4-6 week non-response window, which triggers escalation rather than reduction.
No step size or interval is carried: the source guideline states a total window and a response marker, and does not specify a cadence.
Second line
- Rituximab — Used in primary myositis; SITC does not recommend it here so much as note the experience.SITC advises caution given rituximab's long biological duration — the concern is the length of immunosuppression in a patient with active cancer, not an absolute bar.
- Plasmapheresis or intravenous immunoglobulin (IVIG) — Grade 3 myositis with weakness severely limiting mobility, cardiac or respiratory involvement, or dysphagia — considered alongside the IV methylprednisolone, not after it fails.
- Methotrexate, azathioprine, or mycophenolate mofetil — Symptoms and CK not improving, or worsening, after 4–6 weeks. This is a non-response window, not a taper window.
- · Hospitalisation may be considered for severe weakness
- · Establish whether there is myocardial involvement — it converts the hold into permanent discontinuation
- · The bar for resuming is grade ≤1 while OFF immune suppression, not grade ≤1 on steroids
Escalate when: Respiratory or diaphragmatic involvement, evidence of myocarditis, or no improvement in symptoms and CK by 4–6 weeks.
Grade 4
Discontinue permanentlyAdmitGrade 4 — SITC's musculoskeletal chapter states no grade 4 myositis paragraph. ASCO's cross-organ rule supplies the action: permanent discontinuation of ICPis at grade 4, with an endocrine exception that does not apply here. The management shown is SITC's grade 3 regimen, and the rung says so rather than presenting it as a grade 4 recommendation.
Corticosteroid 1–2 mg/kg/day (intravenous)
Pulse: Methylprednisolone IV 1–2 mg/kg, or a higher-dose bolus — Carried up from SITC's grade 3 escalation criteria, all of which — severe weakness, cardiac or respiratory involvement, dysphagia — are satisfied at grade 4. No grade 4 dose is separately stated.
Taper within 6 weeks or longer, starting once: Not stated for this entity; the ceiling is ASCO's cross-organ minimum taper length.
No step size or interval is carried: the source guideline states a total window and a response marker, and does not specify a cadence.
Second line
- Plasmapheresis or intravenous immunoglobulin (IVIG) — Severe weakness, cardiac or respiratory involvement, or dysphagia.
- Methotrexate, azathioprine, or mycophenolate mofetil — Symptoms and CK not improving, or worsening, after 4–6 weeks.
- · Admission, with respiratory support available for diaphragmatic involvement
- · Permanent discontinuation of the ICI
- · Cardiac assessment maintained — myocarditis is the other route to death in this entity
Escalate when: Already the top rung. Management of established respiratory failure or fulminant overlap myocarditis is beyond what the chapter held here states.
Rechallenge
individualized
This is the one wave-2 card whose chapter describes a route back rather than a stop. SITC holds the ICI at grade 3 until myositis is grade ≤1 while OFF immune suppression — a resumption condition, stated as such — and permanently discontinues only where there is evidence of myocardial involvement. So the stance turns on the cardiac question rather than on the myositis grade, and 'individualized' encodes that fork rather than flattening it. Note what is NOT here: no source cited reports a recurrence rate on resumption, and the 5-year figure SITC quotes runs the other way — half of myositis cases were ongoing or had left sequelae at the end of the observation period.
- · Myositis at grade ≤1 while off immune suppression — SITC's bar, and it is off suppression, not on it
- · No evidence of myocardial involvement; any such evidence makes discontinuation permanent
- · Rheumatology or neurology involvement in the decision
Deliberately not carried
- divergences — Empty because only ONE society chapter for this organ is held here — the same structural limit as the other wave-2 organs. ASCO appears via its cross-organ ladder quoted from the abstract and establishes no musculoskeletal chapter coverage, so 'rheum' stays off ASCO's IRAE_GUIDELINE_ORGANS row. Note that ASCO and SITC do pull in different directions at grade 1 here, which is unusual for these cards, but a divergence needs two sources addressing the same decision and ASCO's is a cross-organ default rather than a myositis position. The interaction is described in the grade 1 gradeDefinition instead of being encoded as a disagreement.
- incidence — The 1% figure is SITC's chapter statement and comes with no cohort, denominator or study. It is carried because it is the only frequency any source held here reports for this entity, with its denominator field saying plainly that none was given. No primary myositis cohort was resolved in this pass — the pharmacovigilance study cited elsewhere in the atlas breaks out the neurological phenotypes, not myositis.
- gradeThreePlus — Null. No source cited here reports a grade ≥3 rate for myositis. The neurological sub-1% high-grade figure carried on the neuro cards is organ-scoped to the nervous system and is not extended here.
- mortality — Null. SITC describes two mechanisms of death — associated myocarditis, and direct diaphragmatic or respiratory involvement — and states no rate for either. The 50% figure in the chapter is not mortality: it is the share of cases ongoing or with sequelae at 5 years, a different measure, and it is carried in the citation's quote and the entry prose rather than in this field.
- onset — No onset window is stated for myositis in any source cited here. The bucket is 'any-time' and all three numeric fields are null. Myasthenia gravis's 29-day median comes from a different study of a different phenotype and is not borrowed, notwithstanding that the two co-occur in 9% of cases.
- ladder[].steroid dose, grades 1-2 — SITC offers oral corticosteroids at these levels and names no dose. The chapter's 1 mg/kg prednisone is written for grade 3, and pulling it down would present a grade 3 dose as a grade 1 recommendation. Both rungs carry kind: unsourced and say a steroid may be offered without a dose being carried.
- ladder[].taper — No taper window, start trigger or step cadence is stated for myositis. Grades 3-4 show ASCO's cross-organ 'at least 4-6 weeks' as an open-ended ceiling labelled as ASCO's, with all three cadence fields null together. The startTrigger text warns against confusing it with SITC's separate 4-6 week NON-RESPONSE window, which triggers escalation to steroid-sparing agents — two 4-6 week intervals in one chapter pointing in opposite directions is a real misreading risk.
- ladder.g4 — SITC's chapter has no grade 4 myositis paragraph. The action comes from ASCO's cross-organ grade 4 rule and the management is SITC's grade 3 regimen carried up, on the basis that every one of SITC's grade 3 escalation criteria is satisfied at grade 4. The gradeDefinition states this rather than presenting the rung as separately sourced.
- guidelinePmids — Left empty although ASCO and SITC are rows in guidelines.ts: their stored keyRecommendation strings are renal-scoped and would surface kidney dosing on a rheumatology card.
Sources
- Brahmer JR, et al. (2021) Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse eventsCited for: Myositis frequency by ICI class, its association with myocarditis and myasthenia gravis at 9% each, the mechanisms of fatality, the symptom range including the asymptomatic-with-raised-CK and symptomatic-with-normal-CK presentations, the 5-year sequelae figure, and the whole graded ladder — the rheumatology or neurology referral, the rule that grade 1 with raised CK and weakness is managed as grade 2, the grade 3 prednisone dose, the IV methylprednisolone and plasmapheresis or IVIG escalation, the hold-until-grade-1 rule with permanent discontinuation on myocardial involvement, the 4-6 week non-response trigger for steroid-sparing agents, and the rituximab caution.Supporting text: the full text
- Schneider BJ, et al. (2021) Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: ASCO Guideline UpdateCited for: The cross-organ ladder. Note what it does NOT say here: its continue-at-grade-1 default excepts neurologic, hematologic and cardiac toxicities and does not except musculoskeletal ones — so unlike the heart and nerve cards, ASCO's grade 1 default does apply to myositis on its face, which is precisely why SITC's raised-CK-and-weakness rule matters.Supporting text: the PubMed abstract (checkable at the link above)
- Johnson DB, et al. (2019) Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study.Cited for: That myasthenia gravis was distinguished from the other neurological phenotypes by frequent CONCURRENT myocarditis and myositis, alongside its early onset and roughly 20% fatality — the pharmacovigilance evidence that this triad co-occurs rather than being three independent toxicities that happen to share symptoms.Supporting text: the PubMed abstract (checkable at the link above)