Introduction
Inclusion body myositis (IBM) is a late onset inflammatory muscle disease (myopathy) with a distinctive pattern of proximal and distal limb weakness. In published series it has accounted for between 17 to 30% of all idiopathic inflammatory myopathies but the true proportion may be much higher (Carpenter 1978; Lotz 1989). In neuromuscular disease referral centres IBM is the commonest acquired myopathy over the age of 50 years. Muscle biopsy is essential for diagnosis and can be pathognomonic. The biopsy usually shows varying degrees of inflammation, with muscle fibres containing rimmed vacuoles. In the majority of cases IBM is a sporadic and isolated disorder. However there are a few cases where IBM occurs in association with an autoimmune disease (Rugiero 1995). In rare instances familial cases of IBM have occurred. A small proportion of these familial cases had histology identical to the sporadic form (Sivakumar 1997) but most are characterised by the absence of inflammatory infiltrates in the muscle biopsy and are more properly called inclusion body myopathy rather than inclusion body myositis (Argov 1984; Kalimo 1988; Cole 1988; Neville 1992). The inflammatory component seen in muscle biopsies of patients with sporadic IBM has prompted treatment with immune suppressive or modulating agents such as corticosteroids, cytotoxic drugs and intravenous gamma globulin.

Review of Treatments Used In IBM Based On Non‐Randomised Trials

Prednisone
A total of 112 patients have been reported in 15 retrospective reports of corticosteroid treatment in IBM with six of these reports being single cases. The cases reported in abstracts by Harati et al (Harati 1986), and Levin et al (Levin 1986) have not been published subsequently (personal communications). One of the four cases reported by Carpenter et al (Carpenter 1978) had been previously reported (Carpenter 1970). The 14 cases reported by Joffe et al are part of a larger series of 113 patients with inflammatory myopathy (Joffe 1993). Fourteen of the 25 retrospective cases described by Leff et al (Leff 1993) had previously been reported as part of a larger retrospective study of the inflammatory myopathies (Love 1991). Many of the retrospective cases reported had trials of corticosteroid treatment before recognition of the diagnosis of IBM, which only became evident as a result of the failure to respond. Prednisone was used in maximum doses of between 20 to 100mg daily with subsequent reduction of dose or alternate day dosing for maintenance therapy. The overall period of treatment ranged from two weeks to two years. The reports generally do not allow exact quantitation of the length of time the maximum dose was prescribed nor how the dose was tapered. In some reports treatment response was based on subjective patient reporting (Leff 1993). Of the 112 patients, 77 either showed no response to corticosteroid treatment or continued to deteriorate despite treatment. Four patients remained stable for a mean follow up of 36 months (Sayers 1992). Three patients showed slight or transient improvement (Hughes 1975; Sayers 1992). Twenty‐three patients showed a partial response, or improvement (Harati 1986; Levin 1986; Cohen 1989; Leff 1993; Joffe 1993) with one of these improving to normal and being maintained at this level at 24 month follow up (Cohen 1989). However it is instructive to note that in one of these reports of a good response to corticosteroid treatment, a second patient is mentioned who refused corticosteroid therapy but nevertheless had a spontaneous 90% improvement in strength (Levin 1986). The patient treated with corticosteroid subsequently deteriorated while the one with spontaneous remission was lost to follow up after one year (Levin personal communication). In one report the improvement was seen in three cases and occurred within days, with a slower improvement in Medical Research Council (MRC) strength scores over subsequent months (Harati 1986). These three cases had a marked inflammatory infiltrate on their muscle biopsies (Harati personal communication).
There have been two prospective open label trials of prednisone (Lindberg 1994; Barohn 1995). Five of the six cases reported in abstracts (Love 1991) have been published subsequently (Barohn 1995) (Lindberg personal communication). Four out of 16 patients showed transient improvement or stabilization of disease on corticosteroid; in one no quantitative testing was performed, in a second patient improvement was confined to the knee extensors. In a third while there was no clinical deterioration, quantitative myometry showed a steady decline throughout the 41 months on treatment (Lindberg 1994). The fourth patient showed a remarkable but short term improvement with a mean 19% gain in the strength of all tested muscles (Lindberg 1994). By contrast a second prospective trial of corticosteroid treatment found a continuing deterioration in all eight patients (Barohn 1995).
In summary, in only rare instances was there evidence that corticosteroids produced sustained, quantitatively demonstrated improvement. At best, "stabilization", usually for a matter of months, was noted. In the rare instances of improvement, studies were uncontrolled. Improvements seen with corticosteroids might not be due to an effect on IBM but on a co‐existing corticosteroid‐responsive disease. Perhaps as many as 25% of patients in this elderly age group might be expected to have a co‐existing condition such as obstructive lung disease, polymyalgia or osteoarthritis that would improve with corticosteroids.

Cytotoxic Therapy
All of the patients treated with cytotoxic therapy had failed a treatment trial of corticosteroid. In many cases the cytotoxic therapy was in addition to corticosteroid treatment.

Cyclophosphamide: of 11 patients with refractory inflammatory myopathy treated with cyclophosphamide, two had IBM (Cronin 1989). One received only one course of treatment which caused severe nausea and vomiting while the other received the planned seven courses. Neither showed any response.

Chlorambucil: two patients who failed to respond to intravenous cyclophosphamide also failed to respond to a trial of chlorambucil (Cronin 1989). Another patient who had failed previous trials of prednisone both alone and in combination with methotrexate, azathioprine or cyclophosphamide improved in terms of function and quantitative muscle strength during the first 15 months of treatment with chlorambucil. The treatment was continued for a three year period but without further improvement. Withdrawal of the chlorambucil after three years had not resulted in any deterioration at the time of the report (Jongen 1995).

Azathioprine: in a retrospective study, three out of 15 patients treated with azathioprine reported some improvement while the rest deteriorated (Leff 1993). Azathioprine was given with methotrexate in one arm of a prospective open, randomized, cross‐over study. Of nine patients, two showed minor improvement and four stabilized during the six month study period (Leff 1993). Azathioprine was one of three additional immunosuppressants given in combination with prednisone to 15 patients. Individual patients were not identified but in this group, one patient stabilized and five had short term benefit (Sayers 1992). Seven patients given azathioprine 150mg/day for an unspecified period showed no response (Lindberg 1994).

Methotrexate: three patients gained a long term remission while on methotrexate (Sayers 1992). In a retrospective study of 12 patients three showed a minor response and one stabilized (Leff 1993). Six of the 10 patients reported by Joffe et al did not respond to methotrexate at all and the rest showed a partial response (Joffe 1993). In a prospective trial two out of nine patients improved and a further four stabilized when treated with methotrexate in combination with azathioprine (Leff 1993).

Cyclosporin: this was one of the additional treatments added to prednisone in 15 patients, with some receiving azathioprine or methotrexate as alternatives. Individual patients were not identified but six were either stable or had short term benefit (Sayers 1992). In a prospective trial in six patients two had to withdraw at four weeks because of side effects and the rest had no benefit (Lindberg 1994).

Total Body Irradiation: four patients have been treated with whole body irradiation (Kelly 1984; Kelly 1986). An initial report (Kelly 1984) suggested partial improvement in one patient. This improvement was subjective and not substantiated by objective measures; the patient deteriorated subsequently (Kelly 1986). The other three patients had no subjective improvement and continued to deteriorate despite treatment (Kelly 1986).

Plasma Exchange: two patients were inadvertently included in a randomised trial of treatment of dermatomyositis and polymyositis; no benefit was noted (Miller 1992).

Leukopheresis: a patient (Dau 1987) showed a "partial response" to leukopheresis which was not maintained. Another patient showed a partial response to apheresis on one occasion but no further details are given (Leff 1993).

Intravenous Immunoglobulin: five prospective open label trials of intravenous immunoglobulin (IVIG) have been reported. The two cases reported by Lindberg et al (Lindberg 1994) were receiving low dose IVIG (400mg/kg/month) on a long term basis for co‐existing common variable immune deficiency, and where also treated with corticosteroid and cyclosporin A. Neither the low dose IVIG nor occasional ten fold dose increases had any effect on their muscle weakness. Three out of four patients responded to high dose IVIG (2g/kg) in one prospective open label trial (Soueidan 1993), while in another similar trial (Amato 1994) there was no response in nine patients. In five patients treated with IVIG for periods of up to six months myometry showed improvement in some muscle groups in some patients, but no functional improvement occurred (Mastaglia 1991; Mastaglia 1993).