Alemtuzumab (ALZ) belongs to the immune reconstitution therapies for relapsing-remitting multiple sclerosis (RRMS). ALZ therapy is associated with an increased risk for secondary autoimmune diseases (SAD), in particular autoimmune thyroid disorders (AITD), but there are also an association to increased risk of immune mediated thrombocytopenic purpura (ITP) and other rare autoimmune disorders.
To investigate the occurrence of SAD, other than AITD, and if auto-antibodies (Ab) could predict the development of non-thyroid SAD (NTSAD).
All RRMS patients in Sweden initiating ALZ (n=124, 74 females) 2014-2019, were consecutively included in this prospective observational study. Plasma samples were obtained prior to ALZ and at 6, 12 and 24 months of follow-up for analyses of glutamic acid decarboxylase Ab (GADAb), antinuclear Ab (ANA), smooth muscle Ab (SMA), antimitochondrial Ab (AMA) and anti-glomerular basement membrane Ab (GBMAb). Monthly blood and urine tests, as well as clinical symptoms, were followed to detect NTSAD.
At mean follow-up of 4.5 (SD 1.6) years 8 patients (6.5%) had developed NTSAD; 5 ITP (4%), 2 neutropenia (2%), and 1 warm antibody haemolytic anaemia (1%). Mean time from baseline to respective NTSAD was 2.1 (SD 1.7) years, 0.6 (SD 0.7) years, and 5.5 years. At their diagnoses positive auto-Ab against platelets, neutrophils and erythrocytes, were present in 1, 0 and 1 ALZ treated patient respectively. No treatment was given for ITP in 3, 1 had intravenous immunoglobulin, romiplostim, corticosteroids, 1 had platelet transfusion, corticosteroids. 1 with neutropenia had granulocyte-colony stimulating factor. No treatment was given for the case with haemolytic anaemia. At baseline 1% (n=1/115) had positive GADAb, 12% (n=13/112) positive ANA, 4% (n=5/112) positive SMA, 0% (n=0/112) positive AMA and 3% (n=3/115) positive GBMAb. Besides these, the number of patients who at least once during the follow-up were positive for the auto-Ab that we regulatory checked for was as follows; 1% (n=1/124) GADAb, 10% (n=13/124) ANA, 3% (n=4/124) SMA, 0% (n=0/124) AMA and 0% (n=0/124) GBMAb, none of these developed any associated NTSAD.
In this real-world cohort study the occurrence of NTSAD, after ALZ treatment, was mainly hematologic, most frequent ITP (4%) and the majority required no treatment. Although the occurrence of auto-Ab was slightly more common after ALZ, compared to the general population, no corresponding NTSAD was found. This was in contrast to thyroid auto-Ab which often precede thyroid disease.