Table 1.
The class of evidence, overall efficacy, common and more significant side effects of immunomodulatory treatment options in MG.
| Class of Evidence (Supportive Studies) |
Overall Outcome | Adverse Effects | Level of Recommendations | |
|---|---|---|---|---|
| Prednisone | II [48,49,50,51,54,65,68,201,202] | Generally effective in ocular and generalized MG | Weight gain, edema, hypertension, hyperglycemia, osteoporosis, cataracts, infections, neuropsychiatric symptoms | Ocular and generalized MG who do not respond to pyridostigmine (level B). Monotherapy in selected patients if they are controlled by a low dose (level B) |
| Azathioprine | II [60,61,62,63,64,65,67,68,69,70] | Effective as a steroid-sparing agent | Leukopenia, hepatotoxicity, pancreatitis, sepsis like idiosyncratic reaction | MG not controlled with low steroid dose (level B) |
| Tacrolimus | II [81,82,83,84,85,86,87,88,90,92] | Effective as a steroid-sparing agent | Well tolerated in doses used for MG. Hypertension, nephrotoxicity, hyperglycemia, hypomagnesemia, tremors, diarrhea, nausea | MG not controlled with low steroid dose (level B) |
| Mycophenolate mofetil | II [94,95,97,98,99,100,101,102,103,104,105,203] | Although earlier results were promising, a subsequent large RCT did not prove steroid-sparing effects, which was attributed by some to issues with the study design, such as inadequate length of the study | Leukopenia, diarrhea, nausea, vomiting, hyperglycemia, headaches | MG not controlled with low steroid dose (level C) |
| Cyclosporine | II [111,112,113,114] | RCT supports the use of cyclosporine, but toxicity more frequent than for tacrolimus. | Nephrotoxicity, hepatotoxicity, hypertension, hypertrichosis, gingival hyperplasia, tremor, optic neuropathy | Level B recommendation, but use is limited by toxicity |
| Methotrexate | II [56,119,120] | Although a large RCT did not prove a steroid-sparing effect, a post hoc analysis suggested some efficacy in secondary endpoints | Hepatotoxicity, pulmonary fibrosis, infection |
Insufficient evidence to recommend use (level U) |
| Cyclophosphamide | II [18,124,125,126] | Effective in patients with refractory generalized MG, including steroid-sparing effects | Bone marrow suppression, hemorrhagic cystitis, alopecia, infections, infertility, nausea and vomiting, neoplasia | MG refractory to other treatments (Level C), concern regarding severe adverse effects, studies conducted before the introduction of newer targeted therapies |
| Rituximab | II [132,133,134,135,136,137,138,139,140,141,142,143,144,145,146,147,149,150,204] | Efficacy more pronounced in MuSK Ab+, but also has shown efficacy and steroid-sparing effects in treatment refractory AChR Ab+ MG. A double blind RCT of rituximab did not prove steroid-sparing effect in AChR Ab+ MG but some have attributed the negative results to the design of the study | Well-tolerated in MG cases. Infusion-related reactions, hypotension, infections, leukopenia, thrombocytopenia, alopecia areata | MuSK Ab+ MG (level B), treatment refractory AChR Ab+ MG (level C) |
| Eculizumab | I [155,156,157,205] | Effective in refractory AChR Ab+ generalized MG, with long term steroid-sparing effects | Well-tolerated. Infusion-related reactions, severe meningococcal infection, other infections, headaches, musculoskeletal pain | Treatment refractory, highly symptomatic AChR Ab+ MG (level B), widespread use limited because of the price. |
| Efgartigimod | I [164,206] | Effective in generalized MG patients who remain highly symptomatic after treatment with pyridostigmine, steroids or NSI | Well-tolerated. Allergic reactions, headache, infections, leukopenia, myalgia | Level B recommendation for patients still symptomatic on pyridostigmine, steroids or NSI. Only approved for AChR Ab + MG, but may work for other MG subtypes, widespread use may be limited because of the price |
| IVIG | II [12,13,14,55,165,166,167,168,169,172,173,174,175,207,208,209,210] | Effective in MG exacerbation and crisis, and in refractory generalized MG, including long term steroid-sparing effects | Headache, urticaria, nephrotoxicity, thrombotic events, myalgia, fever, flu like symptoms |
MG exacerbation or crisis (level B); maintenance therapy in refractory generalized MG (level C); in association with starting steroids or NSI (level C); widespread use limited because of the price |
| PLEX | II [16,166,167,185,187,188,190,209] | Effective in MG exacerbation and crisis, and in refractory generalized MG | Line infection, pneumothorax, hypocalcemia, hypotension, fever, coagulopathy, allergic reactions | MG exacerbation or crisis, (level B), maintenance therapy in refractory generalized MG (level C); use could be limited by availability of expertise and sometimes by need for central venous access |
| Thymectomy | II [7,196,199,200] | Effective in AChR Ab+ patients 18–65 years of age, including steroid-sparing efficacy. Not effective in MuSK Ab+ MG | Surgical complications, postoperative MG exacerbation | Must be carried out in MG with thymoma (level A); Recommended for 18–50-year-old, non-thymomatous AChR Ab + (level B), Not recommended in MuSK Ab + MG; inadequate evidence in double seronegative MG (level U) |
Class of evidence is based on guidelines proposed by “2017 AAN Clinical Practice Guideline Process Manual” [211]. Levels of recommendation: A, effective, must be offered; B, probably effective, should be offered; C, possibly effective, may be offered; U, evidence is insufficient to support or refute the use [211,212,213]. NSI, non-steroid immunosuppressant; RCT, randomized clinical trial.