Stem cell transplant has been shown to be effective for scleroderma in multiple international trials. The latest trial included participants from both US and Canada, where Calgary was one of the participating sites.
These trials included scleroderma patients with the diffuse form of the disease (skin involvement which includes the trunk and/or above the elbows and knees), within around 4 years of disease onset, and most had scleroderma lung disease as well.
Compared with the intravenous medication cyclophosphamide, stem cell transplant led to improved survival – meaning that on average, people lived longer if they had the stem cell transplant versus if they had the cyclophosphamide. Many patients also experienced dramatic improvements in skin thickening, mobility, function, and in their lung disease.
The downside of stem cell transplant included serious infections, and heart or kidney failure. An increased risk of death from the procedure was also observed.
In early 2018, Dr. Murray Baron (McGill University) brought together Canadian rheumatologists, hematologists, and scleroderma patient representatives to review the evidence behind and potential of stem cell transplant therapy in scleroderma.
At this inaugural meeting, they discussed how the procedure works at a cellular level, the various protocols available, the resources available in each province, and how to perform the procedure with the highest yield of benefit with the lowest risk of adverse events.
Plans were set in motion to form a Canadian standardized protocol and criteria for stem cell transplant in scleroderma. Working groups were formed to organize concurrent data collection and research.
In Manitoba, we formed a working group to operationalize the procedure. Dr. David Szwajcer and Dr. Craig Speziali from Hematology as members of the Manitoba Blood and Marrow Transplant Program have experience performing stem cell transplants for other indications.
Along with representatives from Rheumatology (Dr. David Robinson and Dr. Ada Man), the group obtained institutional approval and set up a protocol for performing stem cell transplants in patients with scleroderma here in Winnipeg. We began doing this procedure at the end of 2018 and plan to continue to work together with the Canadian group, with the ultimate goal of providing a safe and effective therapy for scleroderma patients.
A major aim for scleroderma research in Manitoba has been to describe scleroderma as it affects Manitobans. This includes finding out how many people have the disease, understanding how it affects their lives, as well as etiological risk factors possibly unique to Manitoba.
Our first project was to describe the Manitoban scleroderma population. Alireza Almaleki (medical student) and Dr. Ada Man, surveyed all of the rheumatologists in the province and used the hospital database to estimate the prevalence of scleroderma in Manitoba.
We found that there were between 246-261 cases of scleroderma per 1 million population, which was comparable to other estimates in North America, and slightly higher than in BC.
The gender distribution, scleroderma subtype proportions, and the clinical manifestations (organ involvement) were similar to that found in the existing literature. A high proportion of our patients were either current or ex-smokers (45%).
From this prevalence study, we found that certain regions in Manitoba seemed to have a higher than expected density of scleroderma patients.
Dr. Charlie Yang (internal medicine resident), under the supervision of Dr. Annaliese Tisseverasinghe is currently further investigating whether there may be true geographic clustering of scleroderma cases, and whether they may be related to certain environmental exposures.
Manitoba is a participating site for the Phase 3 clinical trial of a cannabinoid receptor 2 (CB2) agonist for the treatment of diffuse cutaneous scleroderma.
CB2 receptors are found in many tissues of the body, including immune cells, fibroblasts, muscle, and endothelial cells. CB2 receptor activation can lead to anti-inflammatory and anti-fibrotic effects, which have been shown in laboratory studies and in mouse studies.
The drug in this trial is not from cannabis but rather is made in the lab and binds to the some common receptors. In the Phase 2 clinical trial of the same this drug, scleroderma patients experienced substantial improvements in their skin thickening and other patient reported outcome measures.
Phase 2 studies are small and this new phase 3 study will help to see if this is truly effective as well as safe in scleroderma.
