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A summary of: From pathophysiology of Sjögren’s syndrome to new clinical trials (EULAR 2018 session)

15 June 2018 Leave a comment

EULAR2018_LogoSometimes the most interesting sessions at a conference do not get the audience they deserve being programmed in smaller rooms and time-wise parallel to big (also interesting) clinical sessions. Today I chose the one in the little rooms at the back over the WIN and HOT major sessions at EULAR 2018 in Amsterdam to listen to a very interesting session with the title mentioned above. It was chaired by Timothy Radstake and Xavier Mariette (which in my opinion is already a recommendation of its own to pick this one from the parallel sessions). Several groups working together in EULAR projects presented their progress and current activities.  One of these  is eSSential – the EULAR Sjogren’s Syndrome Experimental aNd Translational Investigative Alliance Study Group. Francesca Barone (UK) spoke on behalf of this specific EULAR study group and presented an overview of recent advances and current ongoing studies in the field of Sjögren’s syndrome.

Francesca started off with a brief introduction of the pathogenesis of Sjögren’s syndrome (which might indeed be considered as a contradictio in terminis given its complexity). When she started her Sjögren’s syndrome related work there ws always the debate whether Sjögren’s syndrome was a B-cell driven or T-cell driven disease. And it appears neither of them, i,.e. there is no single acting immune cell driving the underlying pathophysiological mechanism of Sjögren’s syndrome. And no single mechanism as well.

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Read more…

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Categories: Uncategorized

A summary of: Rheumatic Musculoskeletal Diseases as comorbidity in cancer patients (EULAR 2018 session)

13 June 2018 Leave a comment

EULAR2018_Logo

By  Professor Maria Suarez-Almazor (USA)

EULAR 2018 – Amsterdam, Wednesday, June 13th.

Immunoediting (ability of cancer to change its genes), a short introduction scope

Cells may develop from normal cells to tumor cells and the immune system tries to eliminate those tumor cells by acting on tumorcells antigens.

There can then be a phase of equilibrium with normal cells and (almost all of the) developing tumor cells that are continuously being eliminated by the immune system.

However at a given point a subfraction of the developed tumor cells can get into a so-called dormancy state*, i.e. their antigens are no longer recognised by the immune system

*Wikipedia; Dormancy is a stage in cancer progression where the cells cease dividing but survive in a quiescent state while waiting for appropriate environmental conditions to begin proliferation again.Quiescence is the state where cells are not dividing but at arrest in the cell cycle in G0-G1. Dormant cancer cells are thought to be present in early tumor progression, in micrometastases, or left behind in minimal residual disease (MRD) after what was thought to be a successful treatment of the primary tumor

Once the cancer is there management of the patient that also has a rheumatic musculoskeletal disease involves balancing between sustained low disease activity of the RMD as well as enhance cancer survival by at the same time keeping anti-tumor treatment effective.

Nice formulated in this tweet by

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The management of #RMD in cancer patients includes controlling the RMD (QoL) + maximizing tumor response (survival) #EULAR2018

There are no guidelines for the treatment of patients with e.g. rheumatoid arthritis and cancer, which is anyway very context dependent in clinical practice and demands a personal approach whilst keeping quality of life in mind.

One of the issues is what to do with biologics treatment in a rheumatoid arthritis patient with a malignancy.  And what about cancer recurrence and when may it be considered safe to resume biologics treatment after the patient has had cancer?

Generally spoken one should distinguish several settings e.g. cancer survivors, patients with chronic (more or less stable) cancer and end-of-life (terminal) cancer patients with a palliative treatment. For cancer survivors there seems (in general) no increased risk to resume (or initiate) biologics treatment for rheumatoid arthritis, especially when five years have passed according to expert opinion. There is no consensus on resuming biologics treatment earlier in these cancer survivor patients with RMD. For the chronic cancer patient with RMD however there is no recommendation at all. It all comes down to a personal and context-dependent approach.

Cancer immunotherapy (checkpoint inhibitors)

e.g. ipimilumab for the treatment of melanoma can have a delayed response in RMD patients. The ipimilumab actually acts in the opossite way as abatacept does. Whereas tumor cells suppress the immunological response (less T-cell interaction with the tumor cells), by enhancing (rather then inhibting like abatacept does) co-stimulation of T-cells the immune response is aggravated. Ipimilumab acts as an anti-CTLA-4 drug. Abatacept as a CTLA-4 agonist.

 

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this tweet was commented on by:

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(…) Kumar and Ballas describe an interesting case of a patient with preexisting myasthenia gravis that acutely worsened after receiving PD-1 blockade. This patient’s myasthenia gravis was unresponsive to multiple immunosuppressant drugs until he received abatacept, a CTLA-4 agonist, which profoundly improved his symptoms. The Food and Drug Administration has approved abatacept for use in patients with rheumatoid arthritis, and we agree that this is an example of how therapies developed for autoimmune disease may be applied in the treatment of immune-related adverse events and how multidisciplinary management can further improve outcomes. Since CTLA-4 blockade has been shown to be beneficial among patients with cancer, it would be important to ensure that abatacept does not have detrimental effects on antitumor immunity if additional patients who have adverse events associated with immune checkpoint blockade are treated with this agent.

[Correspondence Adverse Events Associated with Immune Checkpoint Blockade March 22, 2018 N Engl J Med 2018; 378:1163-1165 DOI: 10.1056/NEJMc1801663 Metrics]

Immunotherapy Related adverse events (irAEs)

Can be mild to life threatening!

The clinical pictures rheumatologist encounter when patients on immunotherapy are referred by the oncologists include:

  1. artritis/arthralgia (an oligoartritis type, an reactive arthritis like type and a rheumatoid arthritis type, the latter possibly already subclinical present before and becoming climical upon immunotherapy (checkpoint inhibitor)
  2. a polymyalgia rheumatica like syndrome which responds to corticosteroids but tends to re-occur upon resuming immunotherapy
  3. a polymyositis like clinical entity without rash and often lacking the accompanying antibodies, cave myocarditis

Management of immunotheraoy related adverse events (recommendations by ioncologists)

  1. early referral to rheumatologists
  2. discontinuation of immunotheraoy (temporary)
  3. immunosuppression starting with corticosteroids at higher dosages than normally would have been given in same rheumatic condition. Tocilizumab might be a promising option that does not seem to affect the immunotherapy efficacy too much, but this is from personal experience of Prof Suarez-Almazor and expert opinion, needs further investigations.

My summary from my handwritten notes having listened to this lecture that gives a scope and a general overview of several relevant aspects. It could well be incomplete and at points not fully correct, feel free to add comments or correct if necessary.

Categories: meeting report

PARA study Rotterdam: >10 years of research on RA and pregnancy

26 September 2015 Leave a comment

The annual 2-day conference of the Dutch Rheumatology Association (NVR) took place last week. One of the invited speakers was Dr RJEM Dolhain (photo) from Erasmus University Medical Center, Rotterdam, the Netherlands. Dr Dolhain provided the audience with a nice overview of what over a decade of research (in the so-called PARA study 2002-2015) in rheumatoid arthritis and pregnancy has yielded so far. The Rotterdam PARA study can be considered as the world’s largest (and ongoing) study of pregnancy related topics in rheumatoid arthritis (follow-up of n=300 of which 250 women have become pregnant). The highlights (i.e. from my own notes during his excellent talk) are listed in this blogpost. Read more…

2013 in review

31 December 2013 Leave a comment

The WordPress.com stats helper monkeys prepared a 2013 annual report for this blog.

Here’s an excerpt:

A San Francisco cable car holds 60 people. This blog was viewed about 2,900 times in 2013. If it were a cable car, it would take about 48 trips to carry that many people.

Click here to see the complete report.

Categories: Algemeen

What is new in Sjögren’s Syndrome (EULAR 2013)

16 June 2013 Leave a comment

Hendrika Bootsma (The Netherlands) at EULAR 2013 Madrid, June 14.

Diagnosis / classification criteria

2013-06-15 11.44.27Criteria must be clear, easy to apply and specific. “The previous AECG classification criteria for Sjögren’s syndrome had been criticized for including subjective tests (symptoms of oral and ocular dryness), physiologic measures that lack specificity, and objective tests that are not diagnostically equivalent. Therefore, the Sjögren’s International Collaborative Clinical Alliance Research Groups proposed an alternative criteria set composed of only objective measures (including lip biopsy). The level of agreement between the preliminary American College of Rheumatology (ACR) criteria and the AECG criteria was high when all objective tests were available to define the AECG criteria but low when subjective tests were allowed to replace the objective tests.” (Bootsma, H., Spijkervet, F. K. L., Kroese, F. G. M. and Vissink, A. (2013), Toward new classification criteria for Sjögren’s syndrome?. Arthritis & Rheumatism, 65: 21–23. doi: 10.1002/art.37701) 

Dealing with a rare disease such as relapsing polychondritis: “food for thought”…

19 May 2013 7 comments

Working as a rheumatologist in an average peripheral hospital means occasionally being confronted with conditions that are quite rare. One of these conditions is Relapsing Polychondritis (RPC), a quite typical condition in terms of how it can be recognised just based on the clinical presentation. However it is a condition not seen that foten at all in a regular rheumatology outpatient clinic.

The weird thing in medicine is that rare conditions happen to be encountered clustered in time in two or three cases shortly after one another, followed by a quite long period in which one does not see the same condition.

That’s also what happened to me for Relapsing Polychondritis. As a trainee in rheumatology I was actually lucky to meet two patients with Relapsing Polychondritis within a month’ s time. Ever since I have not seen a patient with Relapsing Polychondritis untill last month, and guess what…the case was followed by another one in the same month, so again “two-in-a-row” after not having seen RPC in about 4 years. Read more…

My selection of ACR2012 Sjögren’s Syndrome Abstracts (2)

18 November 2012 Leave a comment

This year’s annual scientific meeting of the American College of Rheumatology (ACR) included 76 accepted abstracts on Sjögren’s Syndrome. In this blogpost I name a selection of them that may have clinical relevance for rheumatologists in daily practice together with a few more basic research oriented abstracts that I personally consider of interest. Read more…