Adult inflammatory myopathies are rare conditions. Amongst them, inclusion body myositis (IBM) is considered to be the most common acquired myopathy in adults above 50 years of age, follows a slowly progressive course, and ultimately leads to severe disability. The case of a 57-year-old patient with long standing rheumatoid arthritis (RA) who developed muscle wasting and weakness of the quadriceps femoris after initiation of anti-TNFalpha treatment is presented. Further workup including muscle biopsy revealed IBM. Initiation of rituximab for continuing synovial inflammation led to remission of RA, but no amelioration of muscle weakness was noted. Although cases of IBM in patients with autoimmune disorders have occasionally been reported and are believed to more favourably respond to immunosuppressive treatment, our patient was unresponsive to glucocorticoids. Furthermore, deterioration of muscle strength was noted with both adalimumab and etanercept treatment. Rituximab, not previously used in IBM, successfully controlled RA, but showed no effect on muscle strength. The present case underlines the therapeutic difficulties in IBM and suggests that anti-TNFalpha therapy might even be deleterious. While an early trial of the lymphocyte-depleting antibody alemtuzumab in IBM showed promising results, selective anti-B-cell-therapy remained without effect in our patient.