Mycophenolate mofetil for lupus related myelopathy

Myelopathy is a rare manifestation of systemic lupus erythematosus (SLE). The standard treatment consists of high dose corticosteroids and intravenous pulse cyclophosphamide (CYC).¹,² Despite this, our previous experience indicated that half of the patients with lupus related myelopathy did not respond completely to CYC treatment.³ Moreover, toxicities of CYC are of major concern, particularly severe infections and ovarian failure.⁴ Therefore, less toxic or more effective alternative treatments are needed.

Mycophenolate mofetil (MMF) is a relatively new immunosuppressive agent that has increasingly been used in patients with SLE because of its favourable efficacy and safety.⁵ Controlled trials have confirmed its efficacy in the induction and maintenance treatment of proliferative lupus nephritis.⁶,⁷ MMF has also been reported to be useful in refractory multiple sclerosis.⁸ However, information about the efficacy of MMF in neuropsychiatric SLE is scant. We here report our preliminary experience of the use of combined corticosteroid and MMF in the treatment of lupus related myelopathy.

Three patients who fulfilled the 1982 American College of Rheumatology criteria for SLE and had acute myelopathy were treated with a protocol consisting of high dose corticosteroids (daily intravenous methylprednisolone pulses (15 mg/kg) for 3 days, followed by oral prednisolone 0.6 mg/kg/day for 6 weeks, then tapered by 5 mg/week until <10 mg/day) and MMF (2 g/day for 6 months, followed by 1 g/day in two divided doses). Intravenous immunoglobulin for one course (5 days of 0.4 g/kg) could be given as rescue treatment if the response was suboptimal. Rehabilitative support was also provided. Patients were followed up to determine any relapse of myelitis and adverse events related to drug treatment. Muscle strength was measured by the Medical Research Council grades (0–5). Functional status was assessed by the modified Barthel index (for activity of daily living, score 0–100)⁹ and the expanded disability status scale used in patients with multiple sclerosis (score 0–10).¹⁰

Table 1 shows the clinical characteristics of our patients. All were women and their mean age was 39 years. One patient had previously been refractory to CYC while the other two were reluctant to receive CYC because of the worry about toxicities. Table 2 shows the functional status of the patients before and after treatment for 3 months. Two patients responded partially despite the addition of intravenous immunoglobulin, while one had complete clinical recovery. While receiving maintenance treatment with low dose prednisolone and MMF, two patients had a relapse of myelitis that subsequently responded partially to pulse methylprednisolone and CYC. No patients developed leucopenia or gastrointestinal intolerance to MMF.

Table 1 Clinical characteristics and outcome of the three female patients studied.

Patient No	Age (years)	SLE duration (years)	Previous treatments	aPL	CSF findings	MRI findings	Treatment response and outcome	Adverse effects
1	51	8	Pred, HCQ, CYC (myelopathy refractory to CYC)	+	Lymphocytic pleocytosis ↑ in protein	Normal (brain) Multiple T2 hyperdense signals at thoracic and lumbar cord	Partial response with residual weakness and urge incontinence. Relapse at 8 months and responded partially to pulse CYC	Nil
2	39	0	Nil	–	Lymphocytic pleocytosis ↑ in protein ↓ in sugar	Normal (brain) Longitudinal T2 hyperdense signal spanning from C3 to C8 level (cord)	Partial response after 6 weeks. Relapse at 5 months and responded partially to pulse CYC	One episode of UTI
3	27	2	Pred, HCQ, CSA	–	Lymphocytic pleocytosis ↑ in protein ↓ in sugar Oligoclonal IgG band +ve	Normal (brain, brainstem and spinal cord)	Complete response after 3.5 weeks Remained in remission at 12 months	One episode of herpes zoster at month 2

SLE, systemic lupus erythematosus; aPL, antiphospholipid antibodies (positive for either the anticardiolipin antibody or the lupus anticoagulant on two occasions more than 6 weeks apart); CSF, cerebrospinal fluid; MRI, magnetic resonance imaging; Pred, prednisolone; HCQ, hydroxychloroquine; CYC, cyclophosphamide; CSA, ciclosporin A; UTI, urinary tract infection.

Table 2 Clinical response of patients with lupus related myelopathy.

Clinical response	At presentation	3 Months after treatment
Modified Barthel index (0–100)
Patient 1	54	85
Patient 2	30	94
Patient 3	40	100
EDSS (0–10)
Patient 1	6.5	3.5
Patient 2	8.5	2.5
Patient 3	8.0	0
Lower limb muscle strength (grade 0–5)
Patient 1	R: 3; L: 3	R: 4; L: 4
Patient 2	R: 0; L: 2	R: 5; L: 5
Patient 3	R: 2; L: 2	R: 5; L: 5
Urinary bladder function
Patient 1	Catheter dependent	Mild urge incontinence
Patient 2	Catheter dependent	Post‐voiding RU: <50 ml
Patient 3	Catheter dependent	Normal

EDSS, expanded disability status scale; R, right; L, left; RU, residual urine.

Our experience indicates that although MMF is well tolerated, its efficacy in lupus myelopathy is only modest. Two of our three patients responded partially and their myelopathy relapsed while receiving MMF maintenance treatment. Although complete neurological recovery of myelopathy has not been universally reported with conventional CYC treatment,¹,² controlled trials are needed to compare the relative efficacy of CYC and MMF in this condition. Currently, MMF for lupus myelopathy should be restricted to those who are refractory/intolerant to, or reluctant to receive, CYC.