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CPD

What Have We Learned About Managing Patients With Inflammatory Diseases During the COVID-19 Pandemic?

  • Authors: Tim Raine, MD; Christopher Griffiths, OBE, MD, FMedSci; Georg Schett, MD
  • CPD Released: 7/30/2020
  • THIS ACTIVITY HAS EXPIRED
  • Valid for credit through: 7/30/2021
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Target Audience and Goal Statement

This educational activity is intended for an international audience of non-US gastroenterologists, dermatologists, and rheumatologists.

The goal of this activity is to increase clinicians' knowledge and competence regarding the management of patients with chronic immune-mediated inflammatory diseases (IMIDs) during the coronavirus disease 2019 (COVID-19) pandemic.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Latest information on COVID-19 and its impact on patients with inflammatory diseases
    • Latest information on safety of continuation of biologic therapies in virus-naive or infected patients
  • Have greater competence related to
    • Managing patients with inflammatory disease who are infected with COVID-19


Disclosures

WebMD Global requires each individual who is in a position to control the content of one of its educational activities to disclose any relevant financial relationships occurring within the past 12 months that could create a conflict of interest.


Faculty

  • Timothy Raine, MD

    Gastroenterologist
    Addenbrooke's Hospital
    Cambridge University Hospitals
    Cambridge, UK

    Disclosures

    Disclosure: Timothy Raine, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: AbbVie; Bristol Myers Squibb Company; Celgene; Ferring; Gilead; GlaxoSmithKline; LabGenius; Janssen Pharmaceutical Companies; Mylan; Merck Sharp & Dohme; Novartis; Pfizer; Sandoz; Takeda; UCB
    Received grants for clinical research from: AbbVie

  • Christopher Griffiths, OBE, MD, FMedSci

    Foundation Professor of Dermatology
    Consultant Dermatologist Director
    University of Manchester
    Manchester, UK

    Disclosures

    Disclosure: Christopher Griffiths, OBE, MD, FMedSci, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: AbbVie; Almirall; Celgene; Eli Lilly; Janssen Pharmaceutical Companies; Novartis; Sandoz
    Served as a speaker or a member of a speakers bureau for: AbbVie; Almirall; Celgene; Eli Lilly; Janssen Pharmaceutical Companies; Novartis; UCB
    Received grants for clinical research from: AbbVie; Celgene; Eli Lilly; Janssen Pharmaceutical Companies; Novartis; UCB

  • Georg Schett, MD

    Chief
    Internal Medicine 3
    Universitätsklinikum Erlangen
    Friedrich-Alexander Universität
    Erlangen-Nürnberg, Germany

    Disclosures

    Disclosure: Prof Georg Schett, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: AbbVie; Bristol Myers Squibb Company; Celgene; Chugai; Eli Lilly; Gilead; Janssen Pharmaceutical Companies; Novartis; Roche; UCB
    Served as a speaker or a member of a speakers bureau for: AbbVie; Brisotl Myers Squibb; Celgene; Chugai; Eli Lilly; Gilead; Janssen Pharmaceutical Companies; Novartis; Roche; UCB
    Received grants for clinical research from: Bristol Myers Squibb; Celgene; Chugai; Eli Lilly; Novartis; Roche

Editors

  • Roderick Smith, MS

    Senior Medical Education Director, Medscape, LLC

    Disclosures

    Disclosure: Roderick Smith, MS, has disclosed no relevant financial relationships.

  • Rosalyn Blumenthal, PhD

    Scientific Content Manager, Medscape, LLC

    Disclosures

    Disclosure: Roz Blumenthal, PhD, has disclosed no relevant financial relationships.

Content Reviewer

  • Anjali Mehra, MD

    Lead Medical Education Director

    Disclosures

    Disclosure: Anjali Mehra, MD, has disclosed no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.


Accreditation Statements

    For Physicians

  • The Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the United Kingdom (FPM) has reviewed and approved the content of this educational activity and allocated it 0.50 continuing professional development credits (CPD).

    Contact WebMD Global

For questions regarding the content of this activity, contact the accredited provider for this CME/CE activity noted above. For technical assistance, contact [email protected]


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CPD

What Have We Learned About Managing Patients With Inflammatory Diseases During the COVID-19 Pandemic?

Authors: Tim Raine, MD; Christopher Griffiths, OBE, MD, FMedSci; Georg Schett, MDFaculty and Disclosures
THIS ACTIVITY HAS EXPIRED

CPD Released: 7/30/2020

Valid for credit through: 7/30/2021

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SEGMENT 1

Timothy Raine, MD: Hello. My name is Dr Tim Raine. I'm a gastroenterologist at Addenbrooke's Hospital in Cambridge, United Kingdom. Welcome to this Medscape program titled, "What Have We Learned About Managing Patients With Inflammatory Diseases During the COVID-19 Pandemic?"

Now, COVID-19 has, undoubtedly, had a profound impact on medical practices in hard-hit countries across the whole globe. In addition to treating patients with COVID, many hospitals and clinics have had to make drastic changes to all aspects of everyday patient care. This has had a dramatic impact, in particular, on the way we treat and manage patients with immune mediated inflammatory conditions.

In this 3-part video series, I'll be joined by Dr Christopher Griffiths, a professor of dermatology at the University of Manchester in the United Kingdom and Dr Georg Schett, an expert in rheumatology and immunology at the Friedrich Alexander University in Erlangen-Nürnberg, Germany. We will be discussing key aspects of the management of patients with chronic inflammatory conditions during the COVID-19 pandemic. We'll also take a look towards the future as we attempt to reopen services in midst of uncertainty and the implications of all of this for our hospitals and for our patients.

I want to begin by considering the impact of COVID-19 on our patients with inflammatory bowel disease. If I could choose 1 word to summarize this impact, it will be anxiety. Throughout it, even in a country that's been relatively badly hit by the COVID pandemic, such as the United Kingdom, is the majority of our patients still will not have personally encountered the novel virus. Nevertheless, all of our patients will have been affected by the anxiety that comes with the knowledge that that virus is circulating in our communities. This anxiety touches a number of domains. There are anxieties related to the way that the diseases our patients have may interact with the novel coronavirus and the drugs that they may be taking may interact with the coronavirus. But there's also another layer of anxiety, anxiety around the disruption to their normal interaction with their healthcare professionals, disruption of their access to their regular inflammatory bowel disease team, and even disruption to their regular interactions with their primary care practitioners.

What can we as medical professionals working with patients with inflammatory bowel disease do to alleviate some of this anxiety? Well, certainly some of it comes down to effective communication with our patients and reassuring them to some extent about what we already know. As has been previously discussed in webinars within this Medscape series, we're starting to see data emerging from large scale international registries, which suggests that there's no particular risk signal associated with inflammatory bowel disease and COVID-19 in general.

That said, there may be a small risk associated with patients with active inflammatory bowel disease. For that reason, it's all the more important that we work to keep our patients' disease under control. Importantly, there's little, if any, signal of risk with almost all of the drugs that we routinely use in inflammatory bowel disease with the notable exception of course, corticosteroid therapy, which doesn't appear to be associated with an increased risk of adverse outcomes. That said, even there, there's some confusion with recent results from the Recovery Trial, suggesting that dexamethasone used in dose equivalents, not dissimilar to the sorts of doses of corticosteroids that we typically use for inflammatory bowel disease, may indeed be protective against adverse outcomes and mortality for patients hospitalized with COVID-19.

Despite the urgency and obvious importance of generating research findings in this very fast moving area, it is important that we remain wary of all of the usual problems that are associated with reporting bias that can affect even large scale registry studies. In particular, it's important that we're careful about not departing from evidence for the management of inflammatory bowel disease, which has been built up over many years of careful clinical trials. In general, the principles of IBD management should remain largely unchanged during the pandemic. As I've said already, it remains as important as ever for our patients that we monitor and control their disease flares in a timely manner. It is of course, important as ever that we seek to minimize corticosteroid exposure and consider corticosteroid sparing therapies where appropriate.

We've seen broad international consensus building around these concepts. In particular, relatively early in the pandemic, the international organization for inflammatory bowel disease came together in a series of virtual consensus meetings. Generally, it's a series of guidelines, which effectively reassured us that we should continue business as usual, as much as possible for our patients with the important note that we should seek to avoid a minimized corticosteroid exposure. The IOIBD guidelines also recommended quite appropriately that we should seek and advise patients who acquire the novel coronavirus to discontinue their immunosuppressant medication until such time as they've recovered completely. In the United Kingdom, the British Society of Gastroenterology recently came together in a similar consensus program to pay particular attention to the unique challenge of the patients admitted to hospital with acute severe ulcerative colitis. Again, for the most part, the consensus that was reached reinforced the importance of sticking to established management algorithms, including the upfront use of intravenous high dose corticosteroids, even in patients with positive swab results for COVID, for the novel coronavirus.

Of course it's appropriate to involve appropriate specialists in infectious disease early in the hospitalization of patients who swabbed positive for the novel virus. For patients who failed to respond to initial corticosteroid therapy, there was broad consensus within the group that rescue therapy with infliximab remained appropriate. For those patients who did not respond to rescue therapy, there was no support for the idea that surgery should be delayed. I'll come back to some of the anxieties and concerns around surgery later in this talk. For patients who respond to medical therapy, again, the principle remains that corticosteroids should be tapered in a timely manner and patients transitioned to all of the standard licensed maintenance therapies with a strong emphasis on the role of thromboprophylaxis for patients who have tested positive for the novel virus.

Of course, most of our patients with inflammatory bowel disease are not hospitalized and we remain largely an outpatient specialty. It's perhaps in outpatients that we've seen some of the biggest challenges and changes to the way we work. Of course, as a community, we've shifted very rapidly to using telemedicine where possible then we should remind ourselves that patients still do value human contact either through the use of video consultation or where appropriate, still offering some patients face to face consultations. We know from our patient communities that these are particularly valued by patients who are facing major changes in their treatment management, such as the need for surgery. For these patients, it's important that we find ways to continue to offer them face to face consultations whilst assuring their and our own safety. To this end, well established principles of infection control remain as important as ever.

We tend to screen patients with a telephone call prior to their scheduled appointment time. At the point of arrival for either the presence of symptoms or recent contacts with confirmed cases. All individuals within our hospitals are currently wearing masks, including patients and physicians alike. Of course this doesn't remove us from the important need to continue to observe appropriate social distancing measures and regular hand hygiene. Finally, it's absolutely vital that we limit accompanying persons to only those who are completely essential for a patient's medical care. The same principles that face us in the outpatient clinic have also affected our infusion services. We've managed to maintain a full infusion service throughout the pandemic through exactly these same principles, but that's where possible, we've tried to reduce our dependency upon the infusion service by switching to subcutaneous drugs where appropriate. In fact, although it's not licensed in inflammatory bowel disease, we have switched many of our patients on intravenous infliximab to subcutaneous infliximab, which of course has phase 2 data in inflammatory bowel disease and now has a license in rheumatoid arthritis.

Exactly the same principles of infection control apply within our endoscopy unit. It's interesting to note that we have seen something of a pendulum swinging endoscopy very early in the pandemic, endoscopy activity was very rapidly and almost globally shut down. But of course, we've realized that we have to start to rebuild that capacity as quickly as possible and as safely as possible. In order to do so, we need a series of layers of triage. We have to triage patients according to their risk of carrying the novel virus, and we also have to triage the procedures that patients are undergoing in terms of urgency and risk to the patients of not undergoing those procedures. Not to triage patients is vital that patients are contacted prior to that visits and asked about possible symptoms or contacts with the novel virus.

In Cambridge we're also swabbing all of our patients 72 hours prior to their appointments with a rapid laboratory turn around for the results so that negative patients can be contacted and told to begin preparations for their endoscopy. Now, of course, even with a negative swab and negative symptoms, it's possible that there may be some false negative results, but with current circulating population levels of the virus as low as they currently are in our local community, we recognize that this is a safe measure to continue to adopt, but we're keeping a close eye on the circulating levels of the virus. In other words, the pretest probability within our local community. In order to protect our staff, it's appropriate, the PPE is offered. But again, we know that there's been a global supply problem with PPE, and it's not necessary to use the highest levels of protective equipment for all procedures. In low risk patients who have swabbed negative for the virus undergoing low risk procedures, we use standard fluid resistant surgical masks.

But of course not all patients will have access to endoscopy. Again, there are well-established tools within inflammatory bowel disease for avoiding the need for endoscopy. I'm referring of course, to fecal calprotectin. Even with fecal calprotectin there have been some concerns around the risk of aerosolizing feces, which may carry the virus within analyzing the laboratories. For that reason, we've validated and made available home fecal calprotectin kits that patients can complete and use within the privacy of their own homes. These seem to have a very high degree of acceptability to our patients. Of course, during the months of shutdown, we've built up something of a backlog of urgent referrals, and we're having to work as a team to triage and understand which of those have to go to the front of the queue.

Particular area of challenge has been patients in clinical trials where there's been a need for mandated endoscopy throughout the period of shutdown. This has of course, led to some deviations of protocols and it's important that we liaise closely with our sponsors to understand how this can be overcome. But I think one of the key principle here is that even patients who have missed an essential trial mandated endoscopy is vital that patients continue to have access to their trial medications. We have both a legal, but importantly, a moral obligation to our patients to ensure they have ongoing access to drugs, even with breaches that might previously have led to suspension from clinical trials.

Finally, the other backlog that we've all built up is in patients who are waiting for semi-elective or elective surgery. This is an area of particular concern, both to our patients and our surgical colleagues because of high reported rates of peri-operative mortality, for patients who have acquired the novel virus either prior or immediately after their surgery.

Nevertheless, it's vital that we do start to rebuild our surgical capacity. All of the previously mentioned measures in terms of patient screening and triage apply, but particularly within our surgical units, all of our staff working there are undergoing regular asymptomatic screening so that we can continue to monitor and detect the levels of circulating virus within our health care worker population. Fortunately, these levels are extremely low at the moment, but we have been able to identify the initial clusters that have built up and take appropriate measures to protect both our patients and our staff before those clusters have spread into wider circulating pools.

Some final thoughts, it's absolutely true that we have all faced unprecedented challenges during this pandemic. This has led to substantial anxieties amongst all of us. But of course, particularly amongst our patients. There've been lots of novel solutions throughout this. For example, telemedicine, and some of these solutions will actually be a long-term benefit, both to us as clinicians and to our patients, but it is an unfortunate reality that we're all realizing that shutting down services is perhaps a lot easier than reopening them. Now we need to start to plan and deliver during a recovery phase while accepting a high level of uncertainty about possible future waves of coronavirus infections, and future impacts on our services.

In the next segment, Dr Griffiths will provide his insights on the impact of COVID-19 on the care of dermatology patients with immune mediated inflammatory conditions. Thank you for watching.

SEGMENT 2

Christopher Griffiths, OBE, MD, FMedSci: Hello, I'm Chris Griffiths. I'm foundation professor of dermatology and chairman of the department of dermatology at the University of Manchester and also a practicing consultant dermatologist. In this segment I'll be discussing the impact of COVID-19 on patients with chronic inflammatory skin disease, but particularly focusing in on the skin disease psoriasis.

I'm going to discuss how COVID-19 affects outcomes in people with psoriasis who develop the condition, and conversely how do systemic therapies, and comorbidities, and the demographic variables of people with psoriasis affect the outcomes of the COVID-19 itself. I'm going to preside some data from observational studies published to date, and also global registries which have been set up to try and ascertain the true outcomes with this disease.

The first study I'm going to discuss, and it's 1 of 2 Italian studies, is by Damiani from The Journal of Dermatology Therapy. This is a retrospective study comparing patients in a Milan hospital in Northern Italy, who had psoriasis and who are on systemic therapy, 1193 patients, and they were compared with the background population in Northern Italy in the region of Lombardy. Probably those who are conversant with the COVID-19 pandemic will know that the first recorded cases in Europe were in Northern Italy. This study was run from February the 21st, when the first COVID cases recorded in Italy, through to April the 9th of this year, 2020.

What they found, in a nutshell, was that there is a higher rate of symptomatic coronavirus infection in these patients. Self-quarantined examples was 17 patients, and 5 of these were hospitalized. That's with patients on biologics, but comparing the risk of admission to ICU, intensive care units, between these psoriasis patients and the general population, and also the risk of death, there was seemed to be no increased risk, which is reassuring.

The other study is by Gisondi and colleagues, published in The British Journal of Dermatology, also from Italy. This was a retrospective Italian multicenter study in psoriasis patients on biologic treatment. These are people with moderate to severe disease, and over 5000 patients followed out from February the 20th through to April the 1st, 2020. During that period of the study there were no COVID-19 related deaths. The hospitalization rate for these patients was similar to that observed in the general population. Again, very similar to the previous study, and the incidence of COVID-19 infection per 100,000 was 5.6 compared with 5.9 in the general population. So, again, no significant difference. Both of these studies are reassuring.

I think the real way that we can get accurate data, though, is through psoriasis registries and I'm going to describe 2 global psoriasis registries, as I have the privilege of being involved with. The first is called PsoProtect. This is run by Dr Satveer Mahil, Professor Catherine Smith, Professor Jonathan Barker at Kings College London, and myself here in Manchester. These are clinician reported outcomes in their patients with psoriasis, who they have confirmed diagnosis of COVID-19 or suspected of COVID-19.

At the time of this presentation, more than 370 cases have been reported from around the world. The vast majority are from Europe, but more than 20 countries are represented in this survey. The average age of the patients in the study so far is 50. The vast majority have chronic plaque psoriasis, that's 97%. The vast majority have moderate to severe disease. They're on systemic therapies. As you might expect in patients with psoriasis, the BMI is high at 30, and the average duration of COVID symptoms was 17 days.

Data is available at this stage from 200 patients. The majority of patients were on biologic therapies, whether it be a TNF inhibitors, or inhibitors or IL-17, IL-23 p19, or the p40 inhibitor, ustekinumab, which targets IL-12 and IL-23. Very few were on topical therapies alone. The good news is, is that the vast majority of patients recover fully. There were unfortunately some deaths, but very few, and some had longer term chronic complications such as pulmonary disease.

The other registry is the PsoProtectMe Registry. This is again global, and this is patient self-reported information. Patients themselves can go onto the website and report information, not necessarily whether they have COVID or been suspected having COVID, but how they're coping in this COVID-19 pandemic. In fact, only 5% of the more than 1500 patients from over 39 countries around the world who reported so far had confirmed COVID-19 infection. The vast majority did not go to hospital, only 10% went to hospital. Did the COVID-19 infection clear? Yes, in the vast majority of patients it did respond.

What we're seeing there in those 2 registries is that in the PsoProtect and PsoProtectMe registries is that the disease itself, if anything, may have got a little bit worse, but the vast majority of patients, there was no real difference to their severity of psoriasis if they were infected by COVID. Of course the key question is whether some of the therapies which they are on for their psoriasis, particularly immunomodulatory therapy changes the outcome to the disease.

What I'm going to describe now is data, mainly from what are called immune-mediated inflammatory diseases, which have similar mechanisms and similar treatments to psoriasis. Where it's important to state in the advice that we're giving our patients, there's no evidence today to support discontinuation or changing the dosing regimen of biologic therapies in patients during the COVID-19 pandemic, unless they are demonstrating overt signs of infection. That's what we do for any infection, not just COVID-19. There's no evidence that the use of anti-TNF inhibitors increases the risk of coronavirus infection. In fact, from inflammatory bowel disease studies and from studies in rheumatic diseases, there's some evidence that they might be beneficial in the sense that they may reduce hospitalization.

Conversely, there's evidence from rheumatic diseases that the use of prednisone greater than 10 mg/day, but remember, prednisone isn't used very often for psoriasis, prednisone increases the risk of hospitalization. At present, there's not a lot of data around the use of anti-IL-17 or IL-23 biologics as to whether they affect the outcomes in COVID, but I would surmise that it's going to be similar to the anti-TNF biologics and that it may, at the very least not increase the risk of being admitted to hospital. It may actually reduce it.

But one of the major concerns, and one of the concerns that we've seen in our hospitals here in Manchester and has been replicated around the world is that there's a huge risk of inflammatory skin diseases, such as psoriasis being neglected during the pandemic, leading to disease flares. Patients are reluctant to come to the hospital. They cannot be seen in the current environment. We've already seen that of course, with skin cancer as well, that people with skin cancers are not coming to hospital, they'd rather stay away because they're concerned that hospitals are where they're going to catch COVID.

What are the changes to practice during the COVID pandemic? I've referred to COVID as being a disruptive technology, it's changed the way we manage patients with psoriasis in a very rapid fashion. Teledermatology, which has always been on the sidelines is now very much to the fore in the way that we are managing our patients, either using video conferencing or telephone virtual consultations. I think this in present and in the future will reduce the need for inpatient follow-up visits. I still think there's going to be a need for inpatient visits for making a diagnosis and maybe discussing any significant changes in disease activity.

But I think for those patients who are resuming traditional appointments, the face-to-face appointments, there's going to be still for the foreseeable future a strong emphasis on patient safety, whereas screening, using masks and hygiene, and limiting the number of accompanying persons at the visits. I'm sure that what's going to happen is going to be less routine blood monitoring.

What are my final thoughts? Well, the COVID-19 pandemic has been one of the most significant events of my working lifetime. I'm sure it's true for other medics who I work with.

What we've seen so far is that maybe COVID-19 is not making the psoriasis or atopic dermatitis worse, but we need to monitor that. It's going to require longer term studies, longer term registries, continuing to accrue data, to truly understand the situation, maybe the use of antibody testing to see what is the denominator, how many patients with psoriasis in greater Manchester contracted COVID-19 and how many then developed overt symptomatology. But one thing that this pandemic has done is changed the way that we manage our patients, not just now, but in the future. We'll wait to see whether that is going to be permanent. Where is this going ... to be a little blip and returning back to what we've always done when time moves on?

Thank you for listening. In this final segment, which I'm going to move on to next by Dr Georg Schett, and he will provide insights on the impact of COVID-19 on the care of rheumatology patients with immune-mediated inflammatory conditions.

SEGMENT 3

Prof Georg Schett, MD: Hello, ladies and gentleman. My name is Georg Schett. I'm professor of rheumatology and immunology at the Friedrich-Alexander University of Erlangen, which is in Germany. I want to share with you some thoughts about the impact of COVID-19 in rheumatic and musculoskeletal diseases today.

As you know, we are treating, like in other fields of medicine, like dermatology and gastroenterology, we are treating patients with rheumatoid arthritis, for spondyloarthritis with drugs which affect cytokines. Like for instance, TNF, IL-17, or IL-6. What is very important is to know that these cytokines are the seminal part in the pathogenesis of COVID-19, as they are important in mounting inflammation in the lung when the lung is affected by a SARS-CoV-2. What is also important that many of these cytokines also are important immune surveillance. We are eager always to look at the infection risk in patients treated with inhibitors against TNF, IL-6, or IL-17.

What is quite interesting is we know that there is some small increased risk of a bacterial infection. But interestingly, none of these cytokines inhibitors, particular not TNF alpha blockers, IL-17 blockers, IL-23 blockers, or IL-6 blockers show an increased risk for viral infection. That is quite interesting. The only drug, a class which shows some increased risk of viral infection are JAK inhibitors, particularly the reactivation of herpes zoster virus, has been reported in JAK inhibitor treat the patients. However, what is also very important that there are not many data on respiratory infections. So far it offers no evidence that JAK inhibitors have some adverse role and respiratory infection. Maybe it will be that actually these drugs, which we use in a rheumatic and musculoskeletal disease are not very dangerous in respiratory viral infections.

Therefore it's important to know the current situation. What do we know about the risk of patients with rheumatic and musculoskeletal diseases to suffer from COVID infection? There are several data sets. There is one, a very interesting study from Italy, which is a place of a high prevalence of COVID. These authors identified 65 patients with RNA confirmed COVID-19 infection and RMDs. What they showed is actually, there is no significant difference in these patients with respect to symptoms before admission to the hospital, duration of stay in the hospital or chest x-ray inflammation between RMD patients and controls. What is even more important that patients dying from COVID infection are typically older, also in RMDs than the survivors. What we know well from the general population, that age is an important risk factor for COVID-19 also applies to RMDs, but other potential risk factors were not confirmed.

What is important for instance, that therapy did not impact the severity of COVID infection and did not increase the risk of death due to COVID-19, which is, I think, very important, suggests that the outcome from COVID-19 in RMDs is driven by age and comorbidities, rather than by the rheumatic disease or by the degree of immune intervention.

These findings have essentially been reconfirmed in other strong epidemic center of COVID-19, which is New York City. In a recent publication in The New England Journal of Medicine, the authors analyzed patients with rheumatic diseases and other immune-mediated inflammatory diseases with respect to COVID infection. They showed actually that patients who have mild infection, ambulatory patients, as compared to hospitalized patients with more severe infections, had an equal pattern of cytokine blockers. There was no enrichment of treatment with cytokine blockers in the severely affected patients, suggesting that again, what the Italian studies showed, that it is not impacting the course of COVID-19 whether you use a cytokine blocker or not.

Another study that I think is very important that these data have to be confirmed, but they were confirmed multiple times. There is actually a global rheumatology registry on COVID-19. Some of the data that just published in The Annals of the Rheumatic Diseases on a larger number of patients, over 600 patients. What the authors showed that the risk of hospitalization in this population due to COVID-19 was based again on age, on co-morbidity, and interestingly, also on prednisolone dose. A dose over 10 mg/day, which is considered to be immuno-suppressive, was actually increasing the odds for hospitalization. What is even more important that neither a conventional DMARD therapy, nor a biologic or targeted synthetic DMARD therapy, namely JAK inhibitors, were associated with hospitalization. With anti-TNF alpha agents, the hospitalization rate was even lower. Suggesting again, that we do not think that the immune effect of cytokine inhibitors or other DMARDs used in rheumatic diseases are particularly endangering patients who have severe COVID infection. Even there might be some protective role of these drug with respect to infection.

A very recent study, we have done in our center with over 2000 individuals are investigated, we looked actually at anti-SARS-CoV-2 immune reaction. In healthy controls and patients with immune-mediated inflammatory disease. The bottom line, 2% of the general population develop an IgG response against SARS-CoV-2, whereas the risk is about the same in immune patients taking conventional DMARDs. But very striking, what was very interesting is that people taking cytokine inhibitors, namely TNF inhibitors, JAK inhibitors, IL-6 inhibitors, IL-17 inhibitors or IL-23 inhibitors have a significantly lower risk to develop a SARS-CoV-2 immune response, suggesting that there is a partial protection of these patients from a coronavirus infection. Presumably because they do not mount so much inflammation. Therefore, they cannot develop a full blown immune response against the virus.

What is quite interesting that obviously this risk, is that the relative risk of a patient taking cytokine inhibitors with a rheumatic disease is 0.3, as compared to healthy controls to develop SARS-CoV-2 antibodies, which again, shows that we do not speak of a risk population here with patients with rheumatic diseases. Some of the treatments, actually, may have a positive impact on the risk for developing SARS-CoV-2 infection.

What are the conclusions? Overall, in rheumatic and musculoskeletal diseases, we do not see an increased risk to develop COVID-19. That's very important. Secondly, DMARDs, especially biologics, seem to mitigate the risk for COVID-19, and they're definitely not associated with a more severe disease course. That's concordant in all the studies which have been published so far.

What do we do in case of infection? Well in case of infection, you always have to individually judge whether treatment needs to be stopped. That might be appropriate in some patients, but may not be appropriate in others. Automatically, it probably is not automatic, always necessary to stop, especially the cytokine blocking therapy if there is a mild infection. If it's strong, of course we do that. But I think that has to be judged on the individual basis. What is also what we learned from these data that systemic corticosteroids are probably not very advisable. That's, I think, what we know. We ideally want to mitigate glucocorticoid use in patients with RMDs because of infections. That also seems to be a risk factor for severity of COVID-19.

General recommendations for rheumatologists working in this pandemic at the moment -- I think what we do, we have switched to wearing masks during the consultation, both with respect to the physician and the patient. What we also see, I think is important to manage the flow of the patient, that the waiting times are limited, that the number of patients scheduled for visits are basically carefully chosen, that there is no jamming, if you want, of patients in the waiting rooms and an increase of infection. What is also important that we avoid now that patients come with additional visitors with family members. We try to reduce the number of individual generally in the hospital, who are not patients and we're not doctors, in order to reduce all the infection risk. I think virtual visits are sometimes feasible. They're not always feasible, I should say, that they are trendy. Yes, I think it is possible that we can deal with patients in remission also via a virtual visit. But that's not a universal solution, and we are still dependent to see our patients and to better judge and investigate the patient to better judge how we pursue in the management of the patient.

Therefore, these general recommendations, I think, are very important for us. They are not necessarily different from the general population, but they also apply to us. I think I have shared with you some specific aspects of rheumatic and musculoskeletal disease and COVID-19. I think most stimulating aspect is that we should not be too scared about our treatment because we have no data that our treatments worsen the situations for our patients in this pandemic, I think, which is very stimulating.

I'd like to thank you for participating in this activity. Please continue on to answer the question that follow and complete the evaluation. Thank you.

This is a verbatim transcript and has not been copyedited.

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