The treatment ladder

Low start or high start, and the early dip

Pascuzzi's 1984 series started prednisone at 60–80 mg a day: 80.2% reached remission or marked improvement. Seybold and Drachman built the slowly rising schedule in 1974 to avoid the early worsening seen with 60–100 mg doses. In a cross-sectional study of 590 Japanese patients, a low-dose regimen was more likely than a high-dose one to reach minimal manifestations on ≤5 mg a day (odds ratios 10.4, 2.75 and 1.86 at years 1, 2 and 3). ^{263,416,482,489}

Early worsening was reported in 21% to 48% of patients across older series, 42% of 55 Korean patients within 4 weeks, and 26% of 62 Japanese patients within 2 weeks. The risk factors differ by study: Bae 2006 found older age, severe bulbar symptoms and more severe disease, but not the dose per kg; Kanai 2019 found a start of 40 mg/day or more, thymoma-associated or early-onset MG, and upper-limb weakness. ^29,280,482

These are published regimens quoted for study. The drug, dose and schedule for any person are set by the treating clinician.

Refractory MG

The international consensus defines refractory MG as post-intervention status unchanged or worse after corticosteroids and at least two other immunosuppressants, used at adequate dose for adequate time, with persistent symptoms or side effects that limit function. ⁴⁷⁶

The German guideline uses "highly active" disease instead. Despite adequate therapy, any one of these counts: persistent symptoms of MGFA IIb or worse and/or at least 2 severe exacerbations needing IVIG, plasma exchange or immunoadsorption within a year of diagnosis; MGFA IIa or worse with a severe exacerbation or crisis in the past year; or MGFA IIa or worse for more than 2 years. The Nordic guidance notes that 10–20% of patients stay moderately to severely weak after at least two high-dose immunosuppressants. ^200,549

EPITOME and the eye-only form

EPITOME planned 88 participants but randomised only 11. Treatment failed in 100% on placebo (5) against 17% on prednisone (6), p = 0.02, and minimal manifestation status took a median of 14 weeks at an average of 15 mg a day. ⁴⁴

The 2020 update makes steroids the first immunosuppressant when ptosis or double vision that has not responded to cholinesterase inhibitors is limiting, notes that low doses may suffice, and allows thymectomy for AChR+ ocular MG when immunosuppression is declined, contraindicated or ineffective. In an observational study, generalization at 2 years was 7% with prednisone against 36% without. A 2025 review says ocular MG has no agreed management criteria, and the Nordic guidance leaves it out. ^{200,304,305,381}

RINOMAX against BeatMG

RINOMAX (new-onset generalized MG, 47 patients): one 500 mg dose gave minimal manifestations at 16 weeks in 71% against 29% on placebo, and rescue treatment was needed by 4% against 36%. BeatMG (established, mild to moderate AChR+ MG on prednisone): the steroid-sparing endpoint was met by 60% against 56%, a futility result. ^396,425

A 2025 Cochrane review found little or no steroid-sparing difference but a probable large drop in relapses needing rescue (220 vs 490 per 1,000). In MuSK MG, 58% against 16% reached the favourable outcome in a blinded review, and a meta-analysis found 82% reached minimal manifestations or better. ^76,105,233

IVIG and plasma exchange

The consensus uses them short-term for breathing or swallowing problems, before surgery with significant bulbar weakness, or when a rapid response is needed, and calls them probably equally effective in severe generalized MG. In Barth 2011 (84 patients), 69% improved on IVIG and 65% on plasma exchange by day 14. Which acts faster is still argued: expert consensus favours plasma exchange in crisis, while Barth found no significant difference in QMG change. In MuSK MG, plasma exchange improved 93% and IVIG 61%. ^34,216,476

Difficulty breathing or swallowing is an emergency. See Myasthenic crisis.

Who it is recommended for

MGTX randomised 126 people aged 18–65 with non-thymomatous AChR+ generalized MG: over 3 years QMG averaged 6.15 against 8.99 and prednisone 44 against 60 mg alternate days. The 2020 update says thymectomy should be considered early at ages 18–50, and strongly considered at any age if immunotherapy fails. It finds no indication in MuSK, LRP4 or agrin MG. The age ceiling is debated: MGTX enrolled people up to 65, the 18–50 framing follows a post hoc analysis with no significant benefit at 50 or over (only 17 MGTX participants were that old), and late-onset cohorts disagree. ^{78,228,381,552}

More in Thymectomy over the years.

Complement and FcRn inhibitors

C5 inhibitors (eculizumab, ravulizumab, zilucoplan) are labelled for AChR+ generalized MG and carry a boxed meningococcal warning. FcRn blockers lower IgG; rozanolixizumab and nipocalimab are labelled for AChR+ or MuSK+ disease, and the US efgartigimod IV label was broadened to all adult generalized MG on 8 May 2026. Where guidance places these drugs differs: see the guidance buttons above. ^{137,144,163,165,167,171,173}

More in Complement & FcRn inhibitors.

What "good enough" means

The goals disagree. International: minimal manifestation status or better with no more than grade 1 side effects. Japanese: the same, on prednisolone ≤5 mg a day. German: complete disease control. Nordic: no number, but ambitious goals agreed by patient and doctor. Once goals hold for 6 months to 2 years, the consensus tapers slowly, adjusting no more often than every 3–6 months. ^{200,372,476,549}