Background Connective tissue diseases (CTDs) are a broad spectrum of autoimmune conditions including different entities such as systemic sclerosis (SSc), Sjogren syndrome (SSj), systemic lupus erythematosus (SLE) and autoimmune myositis. There are many patients that do not meet the classification or diagnostic criteria and they fall under the diagnosis of Undifferentiated connective tissue disease (UCTD). Treatment of refractory forms of these could be challenging and clinicians sometimes are forced to try off label drugs such as biologics on the basis of scarce literature support and the experience on different rheumatic disease.
Objectives To evaluate duration of biologic drug administered off label for the treatment of CTD and investigate variables possibly associated to drug suspension.
Methods We used ACE program to search among Mayo Clinic clinical records all the patients that had in their records the words “undifferentiated connective tissue disease” or “lupus” or “myositis” or “Sjogren” or “systemic sclerosis” or “scleroderma”(and acronyms) AND “infliximab” or “etanercept” or “golimumab” or “certolizumab” or “tocilizumab” or “abatacept” or “adalimumab” (and their brand names).
All records were checked for definite diagnosis and patients with uncertain ones where excluded. Also medications were checked, patients without any information about treatments where excluded. All the records of the selected patients were used to collect information about the off label biologic treatment but also clinical, serological and demographic variables.
Results We collected data on 122 patients with connective tissue diseases, some of them had other concomitant autoimmune diseases with indication for biologic treatment (e.g. rheumatoid arthritis, etc). We analyze the group with some CTD alone (n=72) considering SLE (n=18 – 25%), inflammatory myositis (n=22 – 31%) and UCTD (n=32 – 44%). In this group the first biologic was etanercept in 55%, adalimumab in 18%, infliximab in 17%, golimumab in 1% and abatacept in 8%. The 22% tried also a second biologic and 4% a third. We consider for analysis the first treatment.
Mean treatment duration was 0.8 (±1.1)years. In our population 12,5% experienced a flare of CTD, 12,5% had infections, 18% had allergic reactions (of any type). The 44% experienced primary failure, 11% loss of efficacy, 31% had minor adverse events, 14% major ones (possible more than one reason for interruption).
Analysis showed no definite factors correlated with treatment duration or failure or adverse events, No difference due to type of CTD.
Conclusions The study is retrospective and this limits the conclusions to be taken from it, however is one of largest population of off label treatments in CTDs so far. Due to retrospective data we choose as outcome only treatment duration and adverse events, direct outcomes of efficacy were impossible to evaluate. Our results indicates a poor treatment duration of biologics given off label in CTDs with a relevant prevalence of adverse events and failures. It has to be underlined that our population was mainly on TNF blockers.
These data discourage the use of biologics, mainly of TNF blockers in CTDs, even if they still can be considered with caution in very selected cases after failure of the other on label medications.
Disclosure of Interest None declared