Rheumatology News

In my last column, I explained how I’m like Tom Brady. I’m not really. Brady is a Super Bowl–winning quarterback worth over $200 million. No, I’m like Oprah. Well, trying anyway.

Brady and Oprah, in addition to being gazillionaires, have in common that they’re arguably the GOATs (Greatest Of All Time) in their fields. Watching Oprah interview Meghan Markle and Prince Harry was like watching Tom Brady on the jumbotron – she made it look easy. Her ability to create conversation and coax information from guests is hall-of-fame good. But although they are both admirable, trying to be like Brady is useful only for next Thanksgiving when you’re trying to beat your cousins from Massachusetts in touch football. Trying to be like Oprah can help you be better in clinic tomorrow. If we break down what she’s doing, it’s just fundamentals done exceedingly well.

1. Prepare ahead. It’s clear that Oprah has binders of notes about her guests and thoroughly reviewed them before she invites them to sit down. We should do the same. Open the chart and read as much as you can before you open the door. Have important information in your head so you don’t have to break from your interview to refer to it.

2. Sprinkle pleasantry. She’d never start an interview with: So why are you here? Nor should we. Even one nonscripted question or comment can help build a little rapport before getting to the work.

3. Be brief. Oprah gets her question out fast, then gets out of the way. And as a bonus, this is the easiest place to shave a few minutes from your appointments from your own end. Think for a second before you speak and try to find the shortest route to your question. Try to keep your questions to just a sentence or two.

4. Stay on it. Once you’ve discovered something relevant, stay with it, resisting the urge to finish the review of symptoms. This is not just to make a diagnosis, but as importantly, trying to diagnose “the real reason” for the visit. Then, when the question is done, own the transition. Oprah uses: “Let’s move on.” This is a bit abrupt for us, but it can be helpful if used sparingly and gently. I might soften this a little by adding “I want to be sure we have enough time to get through everything for you.”

5. Wait. A few seconds seems an eternity on the air (and in clinic), but sometimes the silent pause is just what’s needed to help the patient expand and share.

6. Be nonjudgmental. Most of us believe we’re pretty good at this, yet, it’s sometimes a blind spot. It’s easy to blame the obese patient for his stasis dermatitis or the hidradenitis patient who hasn’t stop smoking for her cysts. It also helps to be nontransactional. If you make patients feel that you’re asking questions only to extract information, you’ll never reach Oprah level.

7. Be in the moment. It is difficult, but when possible, avoid typing notes while you’re still interviewing. We’re not just there to get the facts, we’re also trying to get the story and that sometimes takes really listening.

I’m no more like Oprah than Brady, of course. But it is more fun to close my eyes and imagine myself being her when I see my next patient. That is, until Thanksgiving. Watch out, Bedards from Attleboro.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

In my last column, I explained how I’m like Tom Brady. I’m not really. Brady is a Super Bowl–winning quarterback worth over $200 million. No, I’m like Oprah. Well, trying anyway.

Brady and Oprah, in addition to being gazillionaires, have in common that they’re arguably the GOATs (Greatest Of All Time) in their fields. Watching Oprah interview Meghan Markle and Prince Harry was like watching Tom Brady on the jumbotron – she made it look easy. Her ability to create conversation and coax information from guests is hall-of-fame good. But although they are both admirable, trying to be like Brady is useful only for next Thanksgiving when you’re trying to beat your cousins from Massachusetts in touch football. Trying to be like Oprah can help you be better in clinic tomorrow. If we break down what she’s doing, it’s just fundamentals done exceedingly well.

1. Prepare ahead. It’s clear that Oprah has binders of notes about her guests and thoroughly reviewed them before she invites them to sit down. We should do the same. Open the chart and read as much as you can before you open the door. Have important information in your head so you don’t have to break from your interview to refer to it.

2. Sprinkle pleasantry. She’d never start an interview with: So why are you here? Nor should we. Even one nonscripted question or comment can help build a little rapport before getting to the work.

3. Be brief. Oprah gets her question out fast, then gets out of the way. And as a bonus, this is the easiest place to shave a few minutes from your appointments from your own end. Think for a second before you speak and try to find the shortest route to your question. Try to keep your questions to just a sentence or two.

4. Stay on it. Once you’ve discovered something relevant, stay with it, resisting the urge to finish the review of symptoms. This is not just to make a diagnosis, but as importantly, trying to diagnose “the real reason” for the visit. Then, when the question is done, own the transition. Oprah uses: “Let’s move on.” This is a bit abrupt for us, but it can be helpful if used sparingly and gently. I might soften this a little by adding “I want to be sure we have enough time to get through everything for you.”

5. Wait. A few seconds seems an eternity on the air (and in clinic), but sometimes the silent pause is just what’s needed to help the patient expand and share.

6. Be nonjudgmental. Most of us believe we’re pretty good at this, yet, it’s sometimes a blind spot. It’s easy to blame the obese patient for his stasis dermatitis or the hidradenitis patient who hasn’t stop smoking for her cysts. It also helps to be nontransactional. If you make patients feel that you’re asking questions only to extract information, you’ll never reach Oprah level.

7. Be in the moment. It is difficult, but when possible, avoid typing notes while you’re still interviewing. We’re not just there to get the facts, we’re also trying to get the story and that sometimes takes really listening.

I’m no more like Oprah than Brady, of course. But it is more fun to close my eyes and imagine myself being her when I see my next patient. That is, until Thanksgiving. Watch out, Bedards from Attleboro.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

In my last column, I explained how I’m like Tom Brady. I’m not really. Brady is a Super Bowl–winning quarterback worth over $200 million. No, I’m like Oprah. Well, trying anyway.

Brady and Oprah, in addition to being gazillionaires, have in common that they’re arguably the GOATs (Greatest Of All Time) in their fields. Watching Oprah interview Meghan Markle and Prince Harry was like watching Tom Brady on the jumbotron – she made it look easy. Her ability to create conversation and coax information from guests is hall-of-fame good. But although they are both admirable, trying to be like Brady is useful only for next Thanksgiving when you’re trying to beat your cousins from Massachusetts in touch football. Trying to be like Oprah can help you be better in clinic tomorrow. If we break down what she’s doing, it’s just fundamentals done exceedingly well.

1. Prepare ahead. It’s clear that Oprah has binders of notes about her guests and thoroughly reviewed them before she invites them to sit down. We should do the same. Open the chart and read as much as you can before you open the door. Have important information in your head so you don’t have to break from your interview to refer to it.

2. Sprinkle pleasantry. She’d never start an interview with: So why are you here? Nor should we. Even one nonscripted question or comment can help build a little rapport before getting to the work.

3. Be brief. Oprah gets her question out fast, then gets out of the way. And as a bonus, this is the easiest place to shave a few minutes from your appointments from your own end. Think for a second before you speak and try to find the shortest route to your question. Try to keep your questions to just a sentence or two.

4. Stay on it. Once you’ve discovered something relevant, stay with it, resisting the urge to finish the review of symptoms. This is not just to make a diagnosis, but as importantly, trying to diagnose “the real reason” for the visit. Then, when the question is done, own the transition. Oprah uses: “Let’s move on.” This is a bit abrupt for us, but it can be helpful if used sparingly and gently. I might soften this a little by adding “I want to be sure we have enough time to get through everything for you.”

5. Wait. A few seconds seems an eternity on the air (and in clinic), but sometimes the silent pause is just what’s needed to help the patient expand and share.

6. Be nonjudgmental. Most of us believe we’re pretty good at this, yet, it’s sometimes a blind spot. It’s easy to blame the obese patient for his stasis dermatitis or the hidradenitis patient who hasn’t stop smoking for her cysts. It also helps to be nontransactional. If you make patients feel that you’re asking questions only to extract information, you’ll never reach Oprah level.

7. Be in the moment. It is difficult, but when possible, avoid typing notes while you’re still interviewing. We’re not just there to get the facts, we’re also trying to get the story and that sometimes takes really listening.

I’m no more like Oprah than Brady, of course. But it is more fun to close my eyes and imagine myself being her when I see my next patient. That is, until Thanksgiving. Watch out, Bedards from Attleboro.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

In my office, one of the many consequences of the COVID-19 pandemic has been a dramatic increase in telephone traffic. I’m sure there are multiple reasons for this, but a major one is calls from patients who remain reluctant to visit our office in person.

Our veteran front-office staff members were adept at handling phone traffic at any level, but most of them retired because of the pandemic. The young folks who replaced them have struggled at times. You would think that millennials, who spend so much time on phones, would have little to learn in that department – until you remember that Twitter, Twitch, and TikTok do not demand polished interpersonal skills.

To address this issue, I have a memo in my office, which I have written, that establishes clear rules for proper professional telephone etiquette. If you want to adapt it for your own office, feel free to do so:

1. You only have one chance to make a first impression. Even now, in the era of texting and email, the telephone remains our primary point of contact with new and long-time patients. The way we answer it determines, to a significant extent, how the community thinks of us, as people and as health care providers.

2. Answer all incoming calls before the third ring.

3. Answer warmly, enthusiastically, and professionally. Since the caller cannot see you, your voice is the only impression of our office a first-time caller will get.

4. Identify yourself and our office immediately. “Good morning, Doctor Eastern’s office. This is _____. How may I help you?” No one should ever have to ask what office they have reached, or to whom they are speaking.

5. Speak softly. This is to ensure confidentiality (more on that next), and because most people find loud telephone voices unpleasant.

6. Maintaining patient confidentiality is a top priority. It makes patients feel secure about being treated in our office, and it is also the law. Keep in mind that patients and others in the office may be able to overhear your phone conversations. Keep your voice down; never use the phone’s hands-free “speaker” function.

Be cautious about all information that is given over the phone. Don’t disclose any personal information unless you are absolutely certain you are talking to the correct patient. If the caller is not the patient, never discuss personal information without the patient’s permission.

7. Adopt a positive vocabulary – one that focuses on helping people. For example, rather than saying, “I don’t know,” say, “Let me find out for you,” or “I’ll find out who can help you with that.”

8. Offer to take a message if the caller has a question or issue you cannot address. Assure the patient that the appropriate staffer will call back later that day. That way, office workflow is not interrupted, and the patient still receives a prompt (and correct) answer.

9. All messages left overnight with the answering service must be returned as early as possible the very next business day. This is a top priority each morning. Few things annoy callers trying to reach their doctors more than unreturned calls. If the office will be closed for a holiday, or a response will be delayed for any other reason, make sure the service knows, and passes it on to patients.

10. Everyone in the office must answer calls when necessary. If you notice that a phone is ringing and the receptionists are swamped, please answer it; an incoming call must never go unanswered.

11. If the phone rings while you are dealing with a patient in person, the patient in front of you is your first priority. Put the caller on hold, but always ask permission before doing so, and wait for an answer. Never leave a caller on hold for more than a minute or two unless absolutely unavoidable.

12. NEVER answer, “Doctor’s office, please hold.” To a patient, that is even worse than not answering at all. No matter how often your hold message tells callers how important they are, they know they are being ignored. Such encounters never end well: Those who wait will be grumpy and rude when you get back to them; those who hang up will be even more grumpy and rude when they call back. Worst of all are those who don’t call back and seek care elsewhere – often leaving a nasty comment on social media besides.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a long-time monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

In my office, one of the many consequences of the COVID-19 pandemic has been a dramatic increase in telephone traffic. I’m sure there are multiple reasons for this, but a major one is calls from patients who remain reluctant to visit our office in person.

Our veteran front-office staff members were adept at handling phone traffic at any level, but most of them retired because of the pandemic. The young folks who replaced them have struggled at times. You would think that millennials, who spend so much time on phones, would have little to learn in that department – until you remember that Twitter, Twitch, and TikTok do not demand polished interpersonal skills.

To address this issue, I have a memo in my office, which I have written, that establishes clear rules for proper professional telephone etiquette. If you want to adapt it for your own office, feel free to do so:

1. You only have one chance to make a first impression. Even now, in the era of texting and email, the telephone remains our primary point of contact with new and long-time patients. The way we answer it determines, to a significant extent, how the community thinks of us, as people and as health care providers.

2. Answer all incoming calls before the third ring.

3. Answer warmly, enthusiastically, and professionally. Since the caller cannot see you, your voice is the only impression of our office a first-time caller will get.

4. Identify yourself and our office immediately. “Good morning, Doctor Eastern’s office. This is _____. How may I help you?” No one should ever have to ask what office they have reached, or to whom they are speaking.

5. Speak softly. This is to ensure confidentiality (more on that next), and because most people find loud telephone voices unpleasant.

6. Maintaining patient confidentiality is a top priority. It makes patients feel secure about being treated in our office, and it is also the law. Keep in mind that patients and others in the office may be able to overhear your phone conversations. Keep your voice down; never use the phone’s hands-free “speaker” function.

Be cautious about all information that is given over the phone. Don’t disclose any personal information unless you are absolutely certain you are talking to the correct patient. If the caller is not the patient, never discuss personal information without the patient’s permission.

7. Adopt a positive vocabulary – one that focuses on helping people. For example, rather than saying, “I don’t know,” say, “Let me find out for you,” or “I’ll find out who can help you with that.”

8. Offer to take a message if the caller has a question or issue you cannot address. Assure the patient that the appropriate staffer will call back later that day. That way, office workflow is not interrupted, and the patient still receives a prompt (and correct) answer.

9. All messages left overnight with the answering service must be returned as early as possible the very next business day. This is a top priority each morning. Few things annoy callers trying to reach their doctors more than unreturned calls. If the office will be closed for a holiday, or a response will be delayed for any other reason, make sure the service knows, and passes it on to patients.

10. Everyone in the office must answer calls when necessary. If you notice that a phone is ringing and the receptionists are swamped, please answer it; an incoming call must never go unanswered.

11. If the phone rings while you are dealing with a patient in person, the patient in front of you is your first priority. Put the caller on hold, but always ask permission before doing so, and wait for an answer. Never leave a caller on hold for more than a minute or two unless absolutely unavoidable.

12. NEVER answer, “Doctor’s office, please hold.” To a patient, that is even worse than not answering at all. No matter how often your hold message tells callers how important they are, they know they are being ignored. Such encounters never end well: Those who wait will be grumpy and rude when you get back to them; those who hang up will be even more grumpy and rude when they call back. Worst of all are those who don’t call back and seek care elsewhere – often leaving a nasty comment on social media besides.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a long-time monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

In my office, one of the many consequences of the COVID-19 pandemic has been a dramatic increase in telephone traffic. I’m sure there are multiple reasons for this, but a major one is calls from patients who remain reluctant to visit our office in person.

Our veteran front-office staff members were adept at handling phone traffic at any level, but most of them retired because of the pandemic. The young folks who replaced them have struggled at times. You would think that millennials, who spend so much time on phones, would have little to learn in that department – until you remember that Twitter, Twitch, and TikTok do not demand polished interpersonal skills.

To address this issue, I have a memo in my office, which I have written, that establishes clear rules for proper professional telephone etiquette. If you want to adapt it for your own office, feel free to do so:

1. You only have one chance to make a first impression. Even now, in the era of texting and email, the telephone remains our primary point of contact with new and long-time patients. The way we answer it determines, to a significant extent, how the community thinks of us, as people and as health care providers.

2. Answer all incoming calls before the third ring.

3. Answer warmly, enthusiastically, and professionally. Since the caller cannot see you, your voice is the only impression of our office a first-time caller will get.

4. Identify yourself and our office immediately. “Good morning, Doctor Eastern’s office. This is _____. How may I help you?” No one should ever have to ask what office they have reached, or to whom they are speaking.

5. Speak softly. This is to ensure confidentiality (more on that next), and because most people find loud telephone voices unpleasant.

6. Maintaining patient confidentiality is a top priority. It makes patients feel secure about being treated in our office, and it is also the law. Keep in mind that patients and others in the office may be able to overhear your phone conversations. Keep your voice down; never use the phone’s hands-free “speaker” function.

Be cautious about all information that is given over the phone. Don’t disclose any personal information unless you are absolutely certain you are talking to the correct patient. If the caller is not the patient, never discuss personal information without the patient’s permission.

7. Adopt a positive vocabulary – one that focuses on helping people. For example, rather than saying, “I don’t know,” say, “Let me find out for you,” or “I’ll find out who can help you with that.”

8. Offer to take a message if the caller has a question or issue you cannot address. Assure the patient that the appropriate staffer will call back later that day. That way, office workflow is not interrupted, and the patient still receives a prompt (and correct) answer.

9. All messages left overnight with the answering service must be returned as early as possible the very next business day. This is a top priority each morning. Few things annoy callers trying to reach their doctors more than unreturned calls. If the office will be closed for a holiday, or a response will be delayed for any other reason, make sure the service knows, and passes it on to patients.

10. Everyone in the office must answer calls when necessary. If you notice that a phone is ringing and the receptionists are swamped, please answer it; an incoming call must never go unanswered.

11. If the phone rings while you are dealing with a patient in person, the patient in front of you is your first priority. Put the caller on hold, but always ask permission before doing so, and wait for an answer. Never leave a caller on hold for more than a minute or two unless absolutely unavoidable.

12. NEVER answer, “Doctor’s office, please hold.” To a patient, that is even worse than not answering at all. No matter how often your hold message tells callers how important they are, they know they are being ignored. Such encounters never end well: Those who wait will be grumpy and rude when you get back to them; those who hang up will be even more grumpy and rude when they call back. Worst of all are those who don’t call back and seek care elsewhere – often leaving a nasty comment on social media besides.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a long-time monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.

Several weeks after getting his second dose of an mRNA vaccine, Aaron Goyang thinks his long bout with COVID-19 has finally come to an end.

Geber86/Getty Images

Mr. Goyang, who is 33 and is a radiology technician in Austin, Tex., thinks he got COVID-19 from some of the coughing, gasping patients he treated last spring.

At the time, testing was scarce, and by the time he was tested – several weeks into his illness – it came back negative. He fought off the initial symptoms but experienced relapse a week later.

Mr. Goyang says that, for the next 8 or 9 months, he was on a roller coaster with extreme shortness of breath and chest tightness that could be so severe it would send him to the emergency department. He had to use an inhaler to get through his workdays.

“Even if I was just sitting around, it would come and take me,” he says. “It almost felt like someone was bear-hugging me constantly, and I just couldn’t get in a good enough breath.”

On his best days, he would walk around his neighborhood, being careful not to overdo it. He tried running once, and it nearly sent him to the hospital.

“Very honestly, I didn’t know if I would ever be able to do it again,” he says.

But Mr. Goyang says that, several weeks after getting the Pfizer vaccine, he was able to run a mile again with no problems. “I was very thankful for that,” he says.

Mr. Goyang is not alone. Some social media groups are dedicated to patients who are living with a condition that’s been known as long COVID and that was recently termed postacute sequelae of SARS-CoV-2 infection (PASC). These patients are sometimes referred to as long haulers.

On social media, patients with PASC are eagerly and anxiously quizzing each other about the vaccines and their effects. Some report that they’ve finally seen their symptoms resolve, giving hope that long COVID might not be a lifelong condition.

Survivor Corps, which has a public Facebook group with 159,000 members, recently took a poll to see whether there was any substance to rumors that those with long COVID were feeling better after being vaccinated.

“Out of 400 people, 36% showed an improvement in symptoms, anywhere between a mild improvement to complete resolution of symptoms,” said Diana Berrent, a long-COVID patient who founded the group. Survivor Corps has become active in patient advocacy and is a resource for researchers studying the new condition.

Ms. Berrent has become such a trusted voice during the pandemic. She interviewed Anthony Fauci, MD, head of the National Institutes of Allergy and Infectious Diseases, last October.

“The implications are huge,” she says.

“Some of this damage is permanent damage. It’s not going to cure the scarring of your heart tissue, it’s not going to cure the irreparable damage to your lungs, but if it’s making people feel better, then that’s an indication there’s viral persistence going on,” says Ms. Berrent.

“I’ve been saying for months and months, we shouldn’t be calling this postacute anything,” she adds.
 

Patients report improvement

Daniel Griffin, MD, PhD, is equally excited. He’s an infectious disease specialist at Columbia University, New York. He says about one in five patients he treated for COVID-19 last year never got better. Many of them, such as Mr. Goyang, were health care workers.

“I don’t know if people actually catch this, but a lot of our coworkers are either permanently disabled or died,” Dr. Griffin says.

Health care workers were also among the first to be vaccinated. Dr. Griffin says many of his patients began reaching out to him about a week or two after being vaccinated “and saying, ‘You know, I actually feel better.’ And some of them were saying, ‘I feel all better,’ after being sick – a lot of them – for a year.”

Then he was getting calls and texts from other doctors, asking, “Hey, are you seeing this?”

The benefits of vaccination for some long-haulers came as a surprise. Dr. Griffin says that, before the vaccines came out, many of his patients were worried that getting vaccinated might overstimulate their immune systems and cause symptoms to get worse.

Indeed, a small percentage of people – about 3%-5%, based on informal polls on social media – report that they do experience worsening of symptoms after getting the shot. It’s not clear why.

Dr. Griffin estimates that between 30% and 50% of patients’ symptoms improve after they receive the mRNA vaccines. “I’m seeing this chunk of people – they tell me their brain fog has improved, their fatigue is gone, the fevers that wouldn’t resolve have now gone,” he says. “I’m seeing that personally, and I’m hearing it from my colleagues.”

Dr. Griffin says the observation has launched several studies and that there are several theories about how the vaccines might be affecting long COVID.
 

An immune system boost?

One possibility is that the virus continues to stimulate the immune system, which continues to fight the virus for months. If that is the case, Dr. Griffin says, the vaccine may be giving the immune system the boost it needs to finally clear the virus away.

Donna Farber, PhD, a professor of microbiology and immunology at Columbia University, has heard the stories, too.

“It is possible that the persisting virus in long COVID-19 may be at a low level – not enough to stimulate a potent immune response to clear the virus, but enough to cause symptoms. Activating the immune response therefore is therapeutic in directing viral clearance,” she says.

Dr. Farber explains that long COVID may be a bit like Lyme disease. Some patients with Lyme disease must take antibiotics for months before their symptoms disappear.

Dr. Griffin says there’s another possibility. Several studies have now shown that people with lingering COVID-19 symptoms develop autoantibodies. There’s a theory that SARS-CoV-2 may create an autoimmune condition that leads to long-term symptoms.

If that is the case, Dr. Griffin says, the vaccine may be helping the body to reset its tolerance to itself, “so maybe now you’re getting a healthy immune response.”

More studies are needed to know for sure.

Either way, the vaccines are a much-needed bit of hope for the long-COVID community, and Dr. Griffin tells his patients who are still worried that, at the very least, they’ll be protected from another SARS-CoV-2 infection.

A version of this article first appeared on Medscape.com.

Several weeks after getting his second dose of an mRNA vaccine, Aaron Goyang thinks his long bout with COVID-19 has finally come to an end.

Geber86/Getty Images

Mr. Goyang, who is 33 and is a radiology technician in Austin, Tex., thinks he got COVID-19 from some of the coughing, gasping patients he treated last spring.

At the time, testing was scarce, and by the time he was tested – several weeks into his illness – it came back negative. He fought off the initial symptoms but experienced relapse a week later.

Mr. Goyang says that, for the next 8 or 9 months, he was on a roller coaster with extreme shortness of breath and chest tightness that could be so severe it would send him to the emergency department. He had to use an inhaler to get through his workdays.

“Even if I was just sitting around, it would come and take me,” he says. “It almost felt like someone was bear-hugging me constantly, and I just couldn’t get in a good enough breath.”

On his best days, he would walk around his neighborhood, being careful not to overdo it. He tried running once, and it nearly sent him to the hospital.

“Very honestly, I didn’t know if I would ever be able to do it again,” he says.

But Mr. Goyang says that, several weeks after getting the Pfizer vaccine, he was able to run a mile again with no problems. “I was very thankful for that,” he says.

Mr. Goyang is not alone. Some social media groups are dedicated to patients who are living with a condition that’s been known as long COVID and that was recently termed postacute sequelae of SARS-CoV-2 infection (PASC). These patients are sometimes referred to as long haulers.

On social media, patients with PASC are eagerly and anxiously quizzing each other about the vaccines and their effects. Some report that they’ve finally seen their symptoms resolve, giving hope that long COVID might not be a lifelong condition.

Survivor Corps, which has a public Facebook group with 159,000 members, recently took a poll to see whether there was any substance to rumors that those with long COVID were feeling better after being vaccinated.

“Out of 400 people, 36% showed an improvement in symptoms, anywhere between a mild improvement to complete resolution of symptoms,” said Diana Berrent, a long-COVID patient who founded the group. Survivor Corps has become active in patient advocacy and is a resource for researchers studying the new condition.

Ms. Berrent has become such a trusted voice during the pandemic. She interviewed Anthony Fauci, MD, head of the National Institutes of Allergy and Infectious Diseases, last October.

“The implications are huge,” she says.

“Some of this damage is permanent damage. It’s not going to cure the scarring of your heart tissue, it’s not going to cure the irreparable damage to your lungs, but if it’s making people feel better, then that’s an indication there’s viral persistence going on,” says Ms. Berrent.

“I’ve been saying for months and months, we shouldn’t be calling this postacute anything,” she adds.
 

Patients report improvement

Daniel Griffin, MD, PhD, is equally excited. He’s an infectious disease specialist at Columbia University, New York. He says about one in five patients he treated for COVID-19 last year never got better. Many of them, such as Mr. Goyang, were health care workers.

“I don’t know if people actually catch this, but a lot of our coworkers are either permanently disabled or died,” Dr. Griffin says.

Health care workers were also among the first to be vaccinated. Dr. Griffin says many of his patients began reaching out to him about a week or two after being vaccinated “and saying, ‘You know, I actually feel better.’ And some of them were saying, ‘I feel all better,’ after being sick – a lot of them – for a year.”

Then he was getting calls and texts from other doctors, asking, “Hey, are you seeing this?”

The benefits of vaccination for some long-haulers came as a surprise. Dr. Griffin says that, before the vaccines came out, many of his patients were worried that getting vaccinated might overstimulate their immune systems and cause symptoms to get worse.

Indeed, a small percentage of people – about 3%-5%, based on informal polls on social media – report that they do experience worsening of symptoms after getting the shot. It’s not clear why.

Dr. Griffin estimates that between 30% and 50% of patients’ symptoms improve after they receive the mRNA vaccines. “I’m seeing this chunk of people – they tell me their brain fog has improved, their fatigue is gone, the fevers that wouldn’t resolve have now gone,” he says. “I’m seeing that personally, and I’m hearing it from my colleagues.”

Dr. Griffin says the observation has launched several studies and that there are several theories about how the vaccines might be affecting long COVID.
 

An immune system boost?

One possibility is that the virus continues to stimulate the immune system, which continues to fight the virus for months. If that is the case, Dr. Griffin says, the vaccine may be giving the immune system the boost it needs to finally clear the virus away.

Donna Farber, PhD, a professor of microbiology and immunology at Columbia University, has heard the stories, too.

“It is possible that the persisting virus in long COVID-19 may be at a low level – not enough to stimulate a potent immune response to clear the virus, but enough to cause symptoms. Activating the immune response therefore is therapeutic in directing viral clearance,” she says.

Dr. Farber explains that long COVID may be a bit like Lyme disease. Some patients with Lyme disease must take antibiotics for months before their symptoms disappear.

Dr. Griffin says there’s another possibility. Several studies have now shown that people with lingering COVID-19 symptoms develop autoantibodies. There’s a theory that SARS-CoV-2 may create an autoimmune condition that leads to long-term symptoms.

If that is the case, Dr. Griffin says, the vaccine may be helping the body to reset its tolerance to itself, “so maybe now you’re getting a healthy immune response.”

More studies are needed to know for sure.

Either way, the vaccines are a much-needed bit of hope for the long-COVID community, and Dr. Griffin tells his patients who are still worried that, at the very least, they’ll be protected from another SARS-CoV-2 infection.

A version of this article first appeared on Medscape.com.

Several weeks after getting his second dose of an mRNA vaccine, Aaron Goyang thinks his long bout with COVID-19 has finally come to an end.

Geber86/Getty Images

Mr. Goyang, who is 33 and is a radiology technician in Austin, Tex., thinks he got COVID-19 from some of the coughing, gasping patients he treated last spring.

At the time, testing was scarce, and by the time he was tested – several weeks into his illness – it came back negative. He fought off the initial symptoms but experienced relapse a week later.

Mr. Goyang says that, for the next 8 or 9 months, he was on a roller coaster with extreme shortness of breath and chest tightness that could be so severe it would send him to the emergency department. He had to use an inhaler to get through his workdays.

“Even if I was just sitting around, it would come and take me,” he says. “It almost felt like someone was bear-hugging me constantly, and I just couldn’t get in a good enough breath.”

On his best days, he would walk around his neighborhood, being careful not to overdo it. He tried running once, and it nearly sent him to the hospital.

“Very honestly, I didn’t know if I would ever be able to do it again,” he says.

But Mr. Goyang says that, several weeks after getting the Pfizer vaccine, he was able to run a mile again with no problems. “I was very thankful for that,” he says.

Mr. Goyang is not alone. Some social media groups are dedicated to patients who are living with a condition that’s been known as long COVID and that was recently termed postacute sequelae of SARS-CoV-2 infection (PASC). These patients are sometimes referred to as long haulers.

On social media, patients with PASC are eagerly and anxiously quizzing each other about the vaccines and their effects. Some report that they’ve finally seen their symptoms resolve, giving hope that long COVID might not be a lifelong condition.

Survivor Corps, which has a public Facebook group with 159,000 members, recently took a poll to see whether there was any substance to rumors that those with long COVID were feeling better after being vaccinated.

“Out of 400 people, 36% showed an improvement in symptoms, anywhere between a mild improvement to complete resolution of symptoms,” said Diana Berrent, a long-COVID patient who founded the group. Survivor Corps has become active in patient advocacy and is a resource for researchers studying the new condition.

Ms. Berrent has become such a trusted voice during the pandemic. She interviewed Anthony Fauci, MD, head of the National Institutes of Allergy and Infectious Diseases, last October.

“The implications are huge,” she says.

“Some of this damage is permanent damage. It’s not going to cure the scarring of your heart tissue, it’s not going to cure the irreparable damage to your lungs, but if it’s making people feel better, then that’s an indication there’s viral persistence going on,” says Ms. Berrent.

“I’ve been saying for months and months, we shouldn’t be calling this postacute anything,” she adds.
 

Patients report improvement

Daniel Griffin, MD, PhD, is equally excited. He’s an infectious disease specialist at Columbia University, New York. He says about one in five patients he treated for COVID-19 last year never got better. Many of them, such as Mr. Goyang, were health care workers.

“I don’t know if people actually catch this, but a lot of our coworkers are either permanently disabled or died,” Dr. Griffin says.

Health care workers were also among the first to be vaccinated. Dr. Griffin says many of his patients began reaching out to him about a week or two after being vaccinated “and saying, ‘You know, I actually feel better.’ And some of them were saying, ‘I feel all better,’ after being sick – a lot of them – for a year.”

Then he was getting calls and texts from other doctors, asking, “Hey, are you seeing this?”

The benefits of vaccination for some long-haulers came as a surprise. Dr. Griffin says that, before the vaccines came out, many of his patients were worried that getting vaccinated might overstimulate their immune systems and cause symptoms to get worse.

Indeed, a small percentage of people – about 3%-5%, based on informal polls on social media – report that they do experience worsening of symptoms after getting the shot. It’s not clear why.

Dr. Griffin estimates that between 30% and 50% of patients’ symptoms improve after they receive the mRNA vaccines. “I’m seeing this chunk of people – they tell me their brain fog has improved, their fatigue is gone, the fevers that wouldn’t resolve have now gone,” he says. “I’m seeing that personally, and I’m hearing it from my colleagues.”

Dr. Griffin says the observation has launched several studies and that there are several theories about how the vaccines might be affecting long COVID.
 

An immune system boost?

One possibility is that the virus continues to stimulate the immune system, which continues to fight the virus for months. If that is the case, Dr. Griffin says, the vaccine may be giving the immune system the boost it needs to finally clear the virus away.

Donna Farber, PhD, a professor of microbiology and immunology at Columbia University, has heard the stories, too.

“It is possible that the persisting virus in long COVID-19 may be at a low level – not enough to stimulate a potent immune response to clear the virus, but enough to cause symptoms. Activating the immune response therefore is therapeutic in directing viral clearance,” she says.

Dr. Farber explains that long COVID may be a bit like Lyme disease. Some patients with Lyme disease must take antibiotics for months before their symptoms disappear.

Dr. Griffin says there’s another possibility. Several studies have now shown that people with lingering COVID-19 symptoms develop autoantibodies. There’s a theory that SARS-CoV-2 may create an autoimmune condition that leads to long-term symptoms.

If that is the case, Dr. Griffin says, the vaccine may be helping the body to reset its tolerance to itself, “so maybe now you’re getting a healthy immune response.”

More studies are needed to know for sure.

Either way, the vaccines are a much-needed bit of hope for the long-COVID community, and Dr. Griffin tells his patients who are still worried that, at the very least, they’ll be protected from another SARS-CoV-2 infection.

A version of this article first appeared on Medscape.com.

Congratulations, you’ve been vaccinated!

It’s been a year like no other, and outpatient psychiatrists turned to Zoom and other telemental health platforms to provide treatment for our patients. Offices sit empty as the dust lands and the plants wilt. Perhaps a few patients are seen in person, masked and carefully distanced, after health screening and temperature checks, with surfaces sanitized between visits, all in accordance with health department regulations. But now the vaccine offers both safety and the promise of a return to a new normal, one that is certain to look different from the normal that was left behind.

Courtesy CDC

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Congratulations, you’ve been vaccinated!

It’s been a year like no other, and outpatient psychiatrists turned to Zoom and other telemental health platforms to provide treatment for our patients. Offices sit empty as the dust lands and the plants wilt. Perhaps a few patients are seen in person, masked and carefully distanced, after health screening and temperature checks, with surfaces sanitized between visits, all in accordance with health department regulations. But now the vaccine offers both safety and the promise of a return to a new normal, one that is certain to look different from the normal that was left behind.

Courtesy CDC

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Congratulations, you’ve been vaccinated!

It’s been a year like no other, and outpatient psychiatrists turned to Zoom and other telemental health platforms to provide treatment for our patients. Offices sit empty as the dust lands and the plants wilt. Perhaps a few patients are seen in person, masked and carefully distanced, after health screening and temperature checks, with surfaces sanitized between visits, all in accordance with health department regulations. But now the vaccine offers both safety and the promise of a return to a new normal, one that is certain to look different from the normal that was left behind.

Courtesy CDC

Dr. Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Telemedicine has had a profound effect upon the practice of rheumatology during the COVID-19 pandemic and will continue to do so afterward, speakers predicted at the 2021 Rheumatology Winter Clinical Symposium.

FatCamera/E+

“Telemedicine will change the way we do business. It already has,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University in Chicago.

“All of a sudden in March of last year we all turned on a dime and went 100% remote, and we made it work. And it has worked well. It’s not the same as seeing people in person, but I’m pretty sure that going forward probably somewhere in the range of 30% of our visits are going to be telemedicine. It’s an incredible way to deal with people who are stable and are driving in from an hour-and-a-half away to get their prescription refilled,” he said.

Conditions well suited for video patient visits are those where the physical exam isn’t informative or necessary, such as polymyalgia rheumatica, axial spondyloarthritis with axial disease only, childhood periodic fever syndromes, and even many cases of rheumatoid arthritis, in Dr. Ruderman’s view.

“People who are stable – maybe not in remission, but we’ve decided they’re at that their target – a lot of those visits can be done remotely. It’s way more efficient. Everybody loves it: We like it, the patients like it. But we have to get to where we can do it better. The technology is clumsy right now,” he said.

“We do need better and smarter platforms,” agreed Alvin F. Wells, MD, PhD, a telerheumatology pioneer who has been involved in digital/video communication with his patients for nearly 6 years. “But the biggest issue is connectivity. Not all of our patients can get on the Internet.”

The telerheumatology paradigm he has used during the pandemic and will continue to use afterward is to see every new patient in the office, then do the follow-up visits virtually.

“They don’t need to come back into the office in 4 weeks. I’ve done my physical exam, ordered the x-rays and lab work. At the virtual 4-week follow-up we go over everything and I tell them if they need to come in for training in giving their injections,” explained Dr. Wells, a rheumatologist in Franklin, Wisc.

“The telemedicine visit doesn’t take the place of an in-person visit, but it allows you to stratify, to say who needs to be seen sooner rather than later,” he added.

While he anticipates that physician-patient virtual visits will continue to be an important part of clinical practice post pandemic, he predicted the major growth areas for telerheumatology once COVID-19 is squashed will be in clinician-to-clinician interactions and remote patient monitoring using smart devices.

Dr. Wells hasn’t gone into the hospital once since the pandemic began. Initially, that was because he didn’t want to deal with the personal protective equipment shortage or expose himself to the virus. Now, it’s because it’s just a more efficient use of his time to conduct virtual – and billable – 15-minute e-consults with clinicians in the hospital.

“I’ve had a lot of appropriate consults with the hospitalists,” he said. He can walk a hospitalist through a real-time physical exam at a gout patient’s bedside and order the right laboratory tests.

“I don’t need to go into the hospital. The interventional radiologist can tap an ankle or toe as well as I can,” the rheumatologist said.

Dermatologist George Martin, MD, rose from the audience to say that while he recognizes that pandemic telemedicine has been a good fit for rheumatologists, it’s been a very different story in dermatology.

“I realize telemedicine works really well when you don’t have to lay your hands on a patient, or when you’re just doing a stable follow-up and talking about test results. But we in dermatology have found as a group that telemedicine is pretty worthless. When patients are trying to send you a video stream of what their melanoma looks like, or maybe it’s a benign seborrheic keratosis, you’re going to hang their life on that? Dermatology is a very hands-on, visual thing, and unless the camera work becomes better telemedicine is worthless, with the exception of a laboratory follow-up or a stable visit where a physical exam is not required,” declared Dr. Martin, who is in private practice in Maui.

Dr. Wells reported serving as a consultant to MiCare Path, a remote health and monitoring company.

bjancin@mdedge.com

Telemedicine has had a profound effect upon the practice of rheumatology during the COVID-19 pandemic and will continue to do so afterward, speakers predicted at the 2021 Rheumatology Winter Clinical Symposium.

FatCamera/E+

“Telemedicine will change the way we do business. It already has,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University in Chicago.

“All of a sudden in March of last year we all turned on a dime and went 100% remote, and we made it work. And it has worked well. It’s not the same as seeing people in person, but I’m pretty sure that going forward probably somewhere in the range of 30% of our visits are going to be telemedicine. It’s an incredible way to deal with people who are stable and are driving in from an hour-and-a-half away to get their prescription refilled,” he said.

Conditions well suited for video patient visits are those where the physical exam isn’t informative or necessary, such as polymyalgia rheumatica, axial spondyloarthritis with axial disease only, childhood periodic fever syndromes, and even many cases of rheumatoid arthritis, in Dr. Ruderman’s view.

“People who are stable – maybe not in remission, but we’ve decided they’re at that their target – a lot of those visits can be done remotely. It’s way more efficient. Everybody loves it: We like it, the patients like it. But we have to get to where we can do it better. The technology is clumsy right now,” he said.

“We do need better and smarter platforms,” agreed Alvin F. Wells, MD, PhD, a telerheumatology pioneer who has been involved in digital/video communication with his patients for nearly 6 years. “But the biggest issue is connectivity. Not all of our patients can get on the Internet.”

The telerheumatology paradigm he has used during the pandemic and will continue to use afterward is to see every new patient in the office, then do the follow-up visits virtually.

“They don’t need to come back into the office in 4 weeks. I’ve done my physical exam, ordered the x-rays and lab work. At the virtual 4-week follow-up we go over everything and I tell them if they need to come in for training in giving their injections,” explained Dr. Wells, a rheumatologist in Franklin, Wisc.

“The telemedicine visit doesn’t take the place of an in-person visit, but it allows you to stratify, to say who needs to be seen sooner rather than later,” he added.

While he anticipates that physician-patient virtual visits will continue to be an important part of clinical practice post pandemic, he predicted the major growth areas for telerheumatology once COVID-19 is squashed will be in clinician-to-clinician interactions and remote patient monitoring using smart devices.

Dr. Wells hasn’t gone into the hospital once since the pandemic began. Initially, that was because he didn’t want to deal with the personal protective equipment shortage or expose himself to the virus. Now, it’s because it’s just a more efficient use of his time to conduct virtual – and billable – 15-minute e-consults with clinicians in the hospital.

“I’ve had a lot of appropriate consults with the hospitalists,” he said. He can walk a hospitalist through a real-time physical exam at a gout patient’s bedside and order the right laboratory tests.

“I don’t need to go into the hospital. The interventional radiologist can tap an ankle or toe as well as I can,” the rheumatologist said.

Dermatologist George Martin, MD, rose from the audience to say that while he recognizes that pandemic telemedicine has been a good fit for rheumatologists, it’s been a very different story in dermatology.

“I realize telemedicine works really well when you don’t have to lay your hands on a patient, or when you’re just doing a stable follow-up and talking about test results. But we in dermatology have found as a group that telemedicine is pretty worthless. When patients are trying to send you a video stream of what their melanoma looks like, or maybe it’s a benign seborrheic keratosis, you’re going to hang their life on that? Dermatology is a very hands-on, visual thing, and unless the camera work becomes better telemedicine is worthless, with the exception of a laboratory follow-up or a stable visit where a physical exam is not required,” declared Dr. Martin, who is in private practice in Maui.

Dr. Wells reported serving as a consultant to MiCare Path, a remote health and monitoring company.

bjancin@mdedge.com

Telemedicine has had a profound effect upon the practice of rheumatology during the COVID-19 pandemic and will continue to do so afterward, speakers predicted at the 2021 Rheumatology Winter Clinical Symposium.

FatCamera/E+

“Telemedicine will change the way we do business. It already has,” observed Eric M. Ruderman, MD, professor of medicine (rheumatology) at Northwestern University in Chicago.

“All of a sudden in March of last year we all turned on a dime and went 100% remote, and we made it work. And it has worked well. It’s not the same as seeing people in person, but I’m pretty sure that going forward probably somewhere in the range of 30% of our visits are going to be telemedicine. It’s an incredible way to deal with people who are stable and are driving in from an hour-and-a-half away to get their prescription refilled,” he said.

Conditions well suited for video patient visits are those where the physical exam isn’t informative or necessary, such as polymyalgia rheumatica, axial spondyloarthritis with axial disease only, childhood periodic fever syndromes, and even many cases of rheumatoid arthritis, in Dr. Ruderman’s view.

“People who are stable – maybe not in remission, but we’ve decided they’re at that their target – a lot of those visits can be done remotely. It’s way more efficient. Everybody loves it: We like it, the patients like it. But we have to get to where we can do it better. The technology is clumsy right now,” he said.

“We do need better and smarter platforms,” agreed Alvin F. Wells, MD, PhD, a telerheumatology pioneer who has been involved in digital/video communication with his patients for nearly 6 years. “But the biggest issue is connectivity. Not all of our patients can get on the Internet.”

The telerheumatology paradigm he has used during the pandemic and will continue to use afterward is to see every new patient in the office, then do the follow-up visits virtually.

“They don’t need to come back into the office in 4 weeks. I’ve done my physical exam, ordered the x-rays and lab work. At the virtual 4-week follow-up we go over everything and I tell them if they need to come in for training in giving their injections,” explained Dr. Wells, a rheumatologist in Franklin, Wisc.

“The telemedicine visit doesn’t take the place of an in-person visit, but it allows you to stratify, to say who needs to be seen sooner rather than later,” he added.

While he anticipates that physician-patient virtual visits will continue to be an important part of clinical practice post pandemic, he predicted the major growth areas for telerheumatology once COVID-19 is squashed will be in clinician-to-clinician interactions and remote patient monitoring using smart devices.

Dr. Wells hasn’t gone into the hospital once since the pandemic began. Initially, that was because he didn’t want to deal with the personal protective equipment shortage or expose himself to the virus. Now, it’s because it’s just a more efficient use of his time to conduct virtual – and billable – 15-minute e-consults with clinicians in the hospital.

“I’ve had a lot of appropriate consults with the hospitalists,” he said. He can walk a hospitalist through a real-time physical exam at a gout patient’s bedside and order the right laboratory tests.

“I don’t need to go into the hospital. The interventional radiologist can tap an ankle or toe as well as I can,” the rheumatologist said.

Dermatologist George Martin, MD, rose from the audience to say that while he recognizes that pandemic telemedicine has been a good fit for rheumatologists, it’s been a very different story in dermatology.

“I realize telemedicine works really well when you don’t have to lay your hands on a patient, or when you’re just doing a stable follow-up and talking about test results. But we in dermatology have found as a group that telemedicine is pretty worthless. When patients are trying to send you a video stream of what their melanoma looks like, or maybe it’s a benign seborrheic keratosis, you’re going to hang their life on that? Dermatology is a very hands-on, visual thing, and unless the camera work becomes better telemedicine is worthless, with the exception of a laboratory follow-up or a stable visit where a physical exam is not required,” declared Dr. Martin, who is in private practice in Maui.

Dr. Wells reported serving as a consultant to MiCare Path, a remote health and monitoring company.

bjancin@mdedge.com

Macrophages are among the most important inflammatory cells in the synovium of patients with rheumatoid arthritis, according to research discussed at the Canadian Arthritis Research Conference: Research with Impact.

Work conducted as part of the Accelerating Medicines Partnership (AMP) Rheumatoid Arthritis and Systemic Lupus Erythematosus (RA/SLE) Network suggests that not only do macrophages play an inflammatory role, but there may also be a subset of macrophages that have a predominantly anti-inflammatory effect.

“These are cells that are really activated and can produce a lot of proinflammatory cytokines, including TNF [tumor necrosis factor],” said Jennifer Howitt Anolik, MD, PhD, associate professor of medicine at the University of Rochester (N.Y.) and cochair of the AMP RA/SLE Network.

“In addition to inflammatory mediators there’s an anti-inflammatory population which may control the disease,” she added, at the virtual meeting, which was sponsored by The Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Health and Arthritis.

There are up to 15 different populations of macrophages found so far as part of a project by Fan Zhang of Brigham and Women’s Hospital and Harvard Medical School in Boston, Dr. Anolik revealed. Of these, three have been shown to be proinflammatory and five have been shown to be anti-inflammatory – including one of particular interest that expresses MERTK, which recent work suggests are lacking in people with RA, compared with a control population of people with osteoarthritis (OA).

Clearly, Dr. Anolik said, there is “lots more work to do to understand how those anti-inflammatory monocytes might work, understand the relationship to treatment response and treatment failure, and how to target them.”
 

AMP RA/SLE Network: Examining RA synovial tissue

What’s unique about the AMP’s work is that it is involving single-cell analytics in which individual cells derived from patients with RA are subjected to an array of RNA sequencing and molecular classification methods.

“If we’re able to define the cells that are driving the disease at the tissue level, this may lead to better therapeutics and more of like a precision medicine approach,” Dr. Anolik said. An important feature of the AMP’s work is that it is based on the use of existing and thus “very informative cohorts” for whom we know a lot about disease characteristics, she said.

The AMP RA/SLE Network officially formed in 2014 and is a public–private partnership between the National Institutes of Health, the Food and Drug Administration, several biopharmaceutical companies, and nonprofit organizations. The task was to try to accelerate discoveries that would lead to better patient care.

“The initial phase [Research Phase 0], was really about developing the procedures in a standardized way,” Dr. Anolik said. “Because we’re looking at patient joint tissue samples, we needed to access that tissue and that required developing needle biopsy approaches.” Synovial biopsy had been pioneered in the United Kingdom and become fairly standard to perform, she added, but this was not an approach that was routinely being used in the United States at the time.

In the next step, Research Phase I, researchers looked at the expression profiles of RA synovial cells in a small group of patients. In all, around 5,000 cells from the joints of up to 20 patients with RA were analyzed. What was apparent was that while there were fibroblasts, monocytes, T cells, and B cells all present to some degree, there was substantial heterogeneity among those subtypes.

“Within all the different immune cells and stromal cells, we found 18 different populations overall,” Dr. Anolik said, giving some of the top-level findings. Both single-cell RNA sequencing and mass cytometry revealed that there were greatly (16-fold) increased numbers of a population of sublining fibroblasts and a 3.3-fold increase in interleukin-1-beta-expressing proinflammatory monocytes. There was a threefold increase in a subset of B cells expressing CD11/T-bet, and a 2.4-fold increase in certain peripheral T cells.

“Interestingly, we were able to pinpoint which cells are making which kinds of inflammatory mediators like inflammatory cytokines,” Dr. Anolik said. Notably, one of the fibroblast populations and one of the B cells were prominent producers of interleukin-6.

The AMP RA/SLE Network is now in Research Phase II, looking at much greater numbers of cells (>5,000) in more than 100 samples from individual patients. It’s a “very comprehensive, big data look at RA,” according to Dr. Anolik.

Research Phase II will also see more rigorous groups of patients being examined, including those who have not had any or much exposure to disease-modifying antirheumatic drugs and those who have inadequately responded to methotrexate or anti-TNF drugs.

Recent AMP RA/SLE Network findings

Recent work by the AMP RA/SLE Network has shown that stromal fibroblasts can become highly inflammatory in RA.

“What’s becoming clear is that these are more than just lining of the joint or structure of the joint, they actually play an active role in the disease,” Dr. Anolik said.

There is a lot of diversity in these fibroblasts but they broadly fall into lining or sublining subtypes. Those that are proinflammatory tend to express markers such as HLA-DR and CD90, and one that is of notable interest is a subgroup of sublining fibroblasts that express Notch3. Indeed, it has been shown that the higher the number of Notch3-expressing fibroblasts there are in the joint, the greater the level of inflammation. Also, mice lacking Notch3 seem to get less arthritis than those with Notch3. This makes Notch3 an interesting potential target that no one had thought of before.

Dr. Anolik noted that some evolving concepts about T cells include evidence showing CD8-postive T cells are more abundant in the joint tissue than previously thought and, together with natural killer (NK) cells, are an important producer of interferon-gamma.

“There are some very interesting CD4 T-cell populations, including an expansion of T peripheral helper cells that may be very important in driving B-cell activation,” Dr. Anolik said. There are also many other clusters of T cells and NK cells that have unknown roles.

Over the past years, Dr. Anolik’s research had focused on the role B cells play in autoimmune disease, and one of the cells of interest are known as age-related B cells, or ABCs. High percentages of ABCs have been found in the RA synovium, and these seem to be related to disease activity as measured by the Disease Activity Score in 28 joints (DAS28). These cells also seem to cluster with some of the T helper cell populations found in the joint. Another interesting target could be B cells expressing a transcription factor known as T-bet. Work in mice suggests that the absence of T-bet B cells could be associated with reduced levels of arthritis.

“One of the things that we’re really interested in about B cells, in addition to their production of autoantibodies, is that they may be important for some of the structural damage that occurs with rheumatoid arthritis,” she said.

T-bet B cells seem to have an effect on both osteoclasts and osteoblasts – activating one while inhibiting the other to have a negative effect on bone overall, she explained. However, knocking out T-bet seems to resolve this, again suggesting that T-bet B cells may be another interesting subpopulation to target.

“Overall, the AMP has been a really interesting approach. This is a massive data set. We are putting the data together now to publish, and it will be available in the public domain,” Dr. Anolik said.

Members of the AMP RA/SLE Network include: AbbVie, the Arthritis Foundation, Bristol‐Myers Squibb, the Foundation for the NIH, the Lupus Foundation of America, the Lupus Research Alliance, Merck Sharp & Dohme, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, the Rheumatology Research Foundation, Sanofi, and Takeda Pharmaceuticals International.

Dr. Anolik had no disclosures.

Macrophages are among the most important inflammatory cells in the synovium of patients with rheumatoid arthritis, according to research discussed at the Canadian Arthritis Research Conference: Research with Impact.

Work conducted as part of the Accelerating Medicines Partnership (AMP) Rheumatoid Arthritis and Systemic Lupus Erythematosus (RA/SLE) Network suggests that not only do macrophages play an inflammatory role, but there may also be a subset of macrophages that have a predominantly anti-inflammatory effect.

“These are cells that are really activated and can produce a lot of proinflammatory cytokines, including TNF [tumor necrosis factor],” said Jennifer Howitt Anolik, MD, PhD, associate professor of medicine at the University of Rochester (N.Y.) and cochair of the AMP RA/SLE Network.

“In addition to inflammatory mediators there’s an anti-inflammatory population which may control the disease,” she added, at the virtual meeting, which was sponsored by The Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Health and Arthritis.

There are up to 15 different populations of macrophages found so far as part of a project by Fan Zhang of Brigham and Women’s Hospital and Harvard Medical School in Boston, Dr. Anolik revealed. Of these, three have been shown to be proinflammatory and five have been shown to be anti-inflammatory – including one of particular interest that expresses MERTK, which recent work suggests are lacking in people with RA, compared with a control population of people with osteoarthritis (OA).

Clearly, Dr. Anolik said, there is “lots more work to do to understand how those anti-inflammatory monocytes might work, understand the relationship to treatment response and treatment failure, and how to target them.”
 

AMP RA/SLE Network: Examining RA synovial tissue

What’s unique about the AMP’s work is that it is involving single-cell analytics in which individual cells derived from patients with RA are subjected to an array of RNA sequencing and molecular classification methods.

“If we’re able to define the cells that are driving the disease at the tissue level, this may lead to better therapeutics and more of like a precision medicine approach,” Dr. Anolik said. An important feature of the AMP’s work is that it is based on the use of existing and thus “very informative cohorts” for whom we know a lot about disease characteristics, she said.

The AMP RA/SLE Network officially formed in 2014 and is a public–private partnership between the National Institutes of Health, the Food and Drug Administration, several biopharmaceutical companies, and nonprofit organizations. The task was to try to accelerate discoveries that would lead to better patient care.

“The initial phase [Research Phase 0], was really about developing the procedures in a standardized way,” Dr. Anolik said. “Because we’re looking at patient joint tissue samples, we needed to access that tissue and that required developing needle biopsy approaches.” Synovial biopsy had been pioneered in the United Kingdom and become fairly standard to perform, she added, but this was not an approach that was routinely being used in the United States at the time.

In the next step, Research Phase I, researchers looked at the expression profiles of RA synovial cells in a small group of patients. In all, around 5,000 cells from the joints of up to 20 patients with RA were analyzed. What was apparent was that while there were fibroblasts, monocytes, T cells, and B cells all present to some degree, there was substantial heterogeneity among those subtypes.

“Within all the different immune cells and stromal cells, we found 18 different populations overall,” Dr. Anolik said, giving some of the top-level findings. Both single-cell RNA sequencing and mass cytometry revealed that there were greatly (16-fold) increased numbers of a population of sublining fibroblasts and a 3.3-fold increase in interleukin-1-beta-expressing proinflammatory monocytes. There was a threefold increase in a subset of B cells expressing CD11/T-bet, and a 2.4-fold increase in certain peripheral T cells.

“Interestingly, we were able to pinpoint which cells are making which kinds of inflammatory mediators like inflammatory cytokines,” Dr. Anolik said. Notably, one of the fibroblast populations and one of the B cells were prominent producers of interleukin-6.

The AMP RA/SLE Network is now in Research Phase II, looking at much greater numbers of cells (>5,000) in more than 100 samples from individual patients. It’s a “very comprehensive, big data look at RA,” according to Dr. Anolik.

Research Phase II will also see more rigorous groups of patients being examined, including those who have not had any or much exposure to disease-modifying antirheumatic drugs and those who have inadequately responded to methotrexate or anti-TNF drugs.

Recent AMP RA/SLE Network findings

Recent work by the AMP RA/SLE Network has shown that stromal fibroblasts can become highly inflammatory in RA.

“What’s becoming clear is that these are more than just lining of the joint or structure of the joint, they actually play an active role in the disease,” Dr. Anolik said.

There is a lot of diversity in these fibroblasts but they broadly fall into lining or sublining subtypes. Those that are proinflammatory tend to express markers such as HLA-DR and CD90, and one that is of notable interest is a subgroup of sublining fibroblasts that express Notch3. Indeed, it has been shown that the higher the number of Notch3-expressing fibroblasts there are in the joint, the greater the level of inflammation. Also, mice lacking Notch3 seem to get less arthritis than those with Notch3. This makes Notch3 an interesting potential target that no one had thought of before.

Dr. Anolik noted that some evolving concepts about T cells include evidence showing CD8-postive T cells are more abundant in the joint tissue than previously thought and, together with natural killer (NK) cells, are an important producer of interferon-gamma.

“There are some very interesting CD4 T-cell populations, including an expansion of T peripheral helper cells that may be very important in driving B-cell activation,” Dr. Anolik said. There are also many other clusters of T cells and NK cells that have unknown roles.

Over the past years, Dr. Anolik’s research had focused on the role B cells play in autoimmune disease, and one of the cells of interest are known as age-related B cells, or ABCs. High percentages of ABCs have been found in the RA synovium, and these seem to be related to disease activity as measured by the Disease Activity Score in 28 joints (DAS28). These cells also seem to cluster with some of the T helper cell populations found in the joint. Another interesting target could be B cells expressing a transcription factor known as T-bet. Work in mice suggests that the absence of T-bet B cells could be associated with reduced levels of arthritis.

“One of the things that we’re really interested in about B cells, in addition to their production of autoantibodies, is that they may be important for some of the structural damage that occurs with rheumatoid arthritis,” she said.

T-bet B cells seem to have an effect on both osteoclasts and osteoblasts – activating one while inhibiting the other to have a negative effect on bone overall, she explained. However, knocking out T-bet seems to resolve this, again suggesting that T-bet B cells may be another interesting subpopulation to target.

“Overall, the AMP has been a really interesting approach. This is a massive data set. We are putting the data together now to publish, and it will be available in the public domain,” Dr. Anolik said.

Members of the AMP RA/SLE Network include: AbbVie, the Arthritis Foundation, Bristol‐Myers Squibb, the Foundation for the NIH, the Lupus Foundation of America, the Lupus Research Alliance, Merck Sharp & Dohme, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, the Rheumatology Research Foundation, Sanofi, and Takeda Pharmaceuticals International.

Dr. Anolik had no disclosures.

Macrophages are among the most important inflammatory cells in the synovium of patients with rheumatoid arthritis, according to research discussed at the Canadian Arthritis Research Conference: Research with Impact.

Work conducted as part of the Accelerating Medicines Partnership (AMP) Rheumatoid Arthritis and Systemic Lupus Erythematosus (RA/SLE) Network suggests that not only do macrophages play an inflammatory role, but there may also be a subset of macrophages that have a predominantly anti-inflammatory effect.

“These are cells that are really activated and can produce a lot of proinflammatory cytokines, including TNF [tumor necrosis factor],” said Jennifer Howitt Anolik, MD, PhD, associate professor of medicine at the University of Rochester (N.Y.) and cochair of the AMP RA/SLE Network.

“In addition to inflammatory mediators there’s an anti-inflammatory population which may control the disease,” she added, at the virtual meeting, which was sponsored by The Arthritis Society, the Canadian Rheumatology Association, and Canada’s Institute of Health and Arthritis.

There are up to 15 different populations of macrophages found so far as part of a project by Fan Zhang of Brigham and Women’s Hospital and Harvard Medical School in Boston, Dr. Anolik revealed. Of these, three have been shown to be proinflammatory and five have been shown to be anti-inflammatory – including one of particular interest that expresses MERTK, which recent work suggests are lacking in people with RA, compared with a control population of people with osteoarthritis (OA).

Clearly, Dr. Anolik said, there is “lots more work to do to understand how those anti-inflammatory monocytes might work, understand the relationship to treatment response and treatment failure, and how to target them.”
 

AMP RA/SLE Network: Examining RA synovial tissue

What’s unique about the AMP’s work is that it is involving single-cell analytics in which individual cells derived from patients with RA are subjected to an array of RNA sequencing and molecular classification methods.

“If we’re able to define the cells that are driving the disease at the tissue level, this may lead to better therapeutics and more of like a precision medicine approach,” Dr. Anolik said. An important feature of the AMP’s work is that it is based on the use of existing and thus “very informative cohorts” for whom we know a lot about disease characteristics, she said.

The AMP RA/SLE Network officially formed in 2014 and is a public–private partnership between the National Institutes of Health, the Food and Drug Administration, several biopharmaceutical companies, and nonprofit organizations. The task was to try to accelerate discoveries that would lead to better patient care.

“The initial phase [Research Phase 0], was really about developing the procedures in a standardized way,” Dr. Anolik said. “Because we’re looking at patient joint tissue samples, we needed to access that tissue and that required developing needle biopsy approaches.” Synovial biopsy had been pioneered in the United Kingdom and become fairly standard to perform, she added, but this was not an approach that was routinely being used in the United States at the time.

In the next step, Research Phase I, researchers looked at the expression profiles of RA synovial cells in a small group of patients. In all, around 5,000 cells from the joints of up to 20 patients with RA were analyzed. What was apparent was that while there were fibroblasts, monocytes, T cells, and B cells all present to some degree, there was substantial heterogeneity among those subtypes.

“Within all the different immune cells and stromal cells, we found 18 different populations overall,” Dr. Anolik said, giving some of the top-level findings. Both single-cell RNA sequencing and mass cytometry revealed that there were greatly (16-fold) increased numbers of a population of sublining fibroblasts and a 3.3-fold increase in interleukin-1-beta-expressing proinflammatory monocytes. There was a threefold increase in a subset of B cells expressing CD11/T-bet, and a 2.4-fold increase in certain peripheral T cells.

“Interestingly, we were able to pinpoint which cells are making which kinds of inflammatory mediators like inflammatory cytokines,” Dr. Anolik said. Notably, one of the fibroblast populations and one of the B cells were prominent producers of interleukin-6.

The AMP RA/SLE Network is now in Research Phase II, looking at much greater numbers of cells (>5,000) in more than 100 samples from individual patients. It’s a “very comprehensive, big data look at RA,” according to Dr. Anolik.

Research Phase II will also see more rigorous groups of patients being examined, including those who have not had any or much exposure to disease-modifying antirheumatic drugs and those who have inadequately responded to methotrexate or anti-TNF drugs.

Recent AMP RA/SLE Network findings

Recent work by the AMP RA/SLE Network has shown that stromal fibroblasts can become highly inflammatory in RA.

“What’s becoming clear is that these are more than just lining of the joint or structure of the joint, they actually play an active role in the disease,” Dr. Anolik said.

There is a lot of diversity in these fibroblasts but they broadly fall into lining or sublining subtypes. Those that are proinflammatory tend to express markers such as HLA-DR and CD90, and one that is of notable interest is a subgroup of sublining fibroblasts that express Notch3. Indeed, it has been shown that the higher the number of Notch3-expressing fibroblasts there are in the joint, the greater the level of inflammation. Also, mice lacking Notch3 seem to get less arthritis than those with Notch3. This makes Notch3 an interesting potential target that no one had thought of before.

Dr. Anolik noted that some evolving concepts about T cells include evidence showing CD8-postive T cells are more abundant in the joint tissue than previously thought and, together with natural killer (NK) cells, are an important producer of interferon-gamma.

“There are some very interesting CD4 T-cell populations, including an expansion of T peripheral helper cells that may be very important in driving B-cell activation,” Dr. Anolik said. There are also many other clusters of T cells and NK cells that have unknown roles.

Over the past years, Dr. Anolik’s research had focused on the role B cells play in autoimmune disease, and one of the cells of interest are known as age-related B cells, or ABCs. High percentages of ABCs have been found in the RA synovium, and these seem to be related to disease activity as measured by the Disease Activity Score in 28 joints (DAS28). These cells also seem to cluster with some of the T helper cell populations found in the joint. Another interesting target could be B cells expressing a transcription factor known as T-bet. Work in mice suggests that the absence of T-bet B cells could be associated with reduced levels of arthritis.

“One of the things that we’re really interested in about B cells, in addition to their production of autoantibodies, is that they may be important for some of the structural damage that occurs with rheumatoid arthritis,” she said.

T-bet B cells seem to have an effect on both osteoclasts and osteoblasts – activating one while inhibiting the other to have a negative effect on bone overall, she explained. However, knocking out T-bet seems to resolve this, again suggesting that T-bet B cells may be another interesting subpopulation to target.

“Overall, the AMP has been a really interesting approach. This is a massive data set. We are putting the data together now to publish, and it will be available in the public domain,” Dr. Anolik said.

Members of the AMP RA/SLE Network include: AbbVie, the Arthritis Foundation, Bristol‐Myers Squibb, the Foundation for the NIH, the Lupus Foundation of America, the Lupus Research Alliance, Merck Sharp & Dohme, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, the Rheumatology Research Foundation, Sanofi, and Takeda Pharmaceuticals International.

Dr. Anolik had no disclosures.

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

A version of this article first appeared on Medscape.com.

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

A version of this article first appeared on Medscape.com.

New pills to treat patients with COVID-19 are currently in midstage clinical trials and, if successful, could be ready by the end of the year.

Only one treatment – remdesivir (Veklury) – has been fully approved by the U.S. Food and Drug Administration for patients in the hospital and it must be administered intravenously.

Hopes for a day when patients with COVID-19 can take a pill to rid their bodies of the virus got a boost when early trial results were presented at a medical conference.

Interim phase 2 results for the oral experimental COVID-19 drug molnupiravir, designed to do for patients with COVID-19 what oseltamivir (Tamiflu) can do for patients with the flu, were presented at the Conference on Retroviruses and Opportunistic Infections 2021 Annual Meeting, as reported by this news organization.

In the small study, the pill significantly reduced infectious virus in patients who were symptomatic and had tested positive for COVID-19 during the previous 4 days but were not hospitalized.

After 5 days of treatment, no participants who received molnupiravir had detectable virus, whereas 24% who received placebo did.

Two other oral agents are being developed by RedHill Biopharma: one for severe COVID-19 infection for hospitalized patients and one for patients at home with mild infection.

The first, opaganib (Yeliva), proceeded to a phase 2/3 global trial for hospitalized patients after the company announced top-line safety and efficacy data in December. In phase 2, the drug was shown to be safe in patients requiring oxygen and effectively reduced the need for oxygen by the end of the treatment period.

A key feature is that it is both an antiviral and an anti-inflammatory, Gilead Raday, RedHill’s chief operating officer, said in an interview. Data are expected midyear on its performance in 464 patients. The drug is being tested on top of remdesivir or in addition to dexamethasone.

The second, upamostat (RHB-107), is currently undergoing a phase 2/3 trial in the United States and is being investigated for use in nonhospitalized COVID-19 patients.

“I would expect data to be available in the second half of this year,” Mr. Raday said.

Upamostat is a novel serine protease inhibitor expected to be effective against emerging variants because it targets human cell factors involved in viral entry, according to the company.

Other drugs are being investigated in trials that are in earlier stages.
 

Urgent need for oral agents

Infectious disease specialists are watching the move toward a COVID-19 pill enthusiastically.

“We badly need an oral treatment option for COVID,” said Sarah Doernberg, MD, an infectious disease specialist from the University of California, San Francisco.

“It’s a real gap in our armamentarium for COVID in outpatient treatment, which is where most who contract COVID-19 will seek care,” she said in an interview.

Although some studies have shown the benefit of monoclonal antibodies for prevention and early treatment, there are major logistical issues because all the current options require IV administration, she explained.

“If we had a pill to treat early COVID, especially in high-risk patients, it would fill a gap,” she said, noting that a pill could help people get better faster and prevent hospital stays.

Studies of molnupiravir suggest that it decreases viral shedding in the first few days after COVID infection, Dr. Doernberg reported.

There is excitement around the drug, but it will be important to see whether the results translate into fewer people requiring hospital admission and whether people feel better faster.

“I want to see the clinical data,” Dr. Doernberg said.

She will also be watching for the upamostat and opaganib results in the coming weeks.

“If these drugs are successful, I think it’s possible we could use them – maybe under an emergency use authorization – this year,” she said.

Once antiviral pills are a viable option for COVID-19 treatment, questions will arise about their use, she said.

One question is whether patients who are getting remdesivir in the hospital and are ready to leave after 5 days should continue treatment with antiviral pills at home.

Another is whether the pills – if they are shown to be effective – will be helpful for COVID post exposure. That use would be important for people who do not have COVID-19 but who are in close contact with someone who does, such as a member of their household.

“We have that model,” Dr. Doernberg said. “We know that oseltamivir can be used for postexposure prophylaxis and can help to prevent development of clinical disease.”

But she cautioned that a challenge with COVID is that people are contagious very early. A pill would need to come with the ability to test for COVID-19 early and get patients linked to care immediately.

“Those are not small challenges,” she said.
 

Vaccines alone won’t end the COVID threat

Treatments are part of the “belt-and-suspenders” approach, along with vaccines to combat COVID-19, Dr. Doernberg said.

“We’re not going to eradicate COVID,” she said. “We’re still going to need treatments for people who either don’t respond to the vaccine or haven’t gotten the vaccine or developed disease despite the vaccine.”

Oral formulations are desperately needed, agreed Kenneth Johnson, PhD, professor of molecular biosciences at the University of Texas at Austin.

Right now, remdesivir treatments involve patients being hooked up to an IV for 30-120 minutes each day for 5 days. And the cost of a 5-day course of remdesivir ranges from $2340 to $3120 in the United States.

“We’re hoping we can come up with something that is a little bit easier to administer, and without as many concerns for toxic side effects,” he said.

Dr. Johnson’s team at UT-Austin recently made a key discovery about the way remdesivir stops the replication of viral RNA.

The understanding of where the virus starts to replicate in the infection chain of events and how and where it reacts with remdesivir might lead to the development of better, more concentrated pill forms of antivirals in the future, with fewer toxicities, he said.

The team used a lab dish to recreate the step-by-step process that occurs when a patient who is infected with SARS-CoV-2 receives remdesivir.

The discovery was published online in Molecular Cell in January and will be printed in the April issue of the journal.

The discovery won’t lead to an effective COVID-19 pill for our current crisis, but will be important for the next generation of drugs needed to deal with future coronaviruses, Dr. Johnson explained.

And there will be other coronaviruses, he said, noting that this one is the third in 20 years to jump from animals to humans. “It’s just a matter of time,” he said.

A version of this article first appeared on Medscape.com.

Sub-subspecialization would be counterproductive: Orrin M. Troum, MD

The much-discussed looming rheumatology workforce shortage is actually here already. And it’s going to worsen rapidly. Add to that the striking geographic maldistribution of rheumatologists across the United States, and it makes little sense for some rheumatologists to declare they’re only going to see patients with psoriatic arthritis, or gout, or lupus. Such sub-subspecialization will only worsen the workforce problem, Orrin M. Troum, MD, asserted at the 2021 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Besides, surveys indicate that most rheumatologists like what they do now, despite their status as the lowest-paid subspecialists within internal medicine. They enjoy a sense of satisfaction stemming from their ability to help patients with chronic debilitating diseases turn their lives around as a result of revolutionary treatment advances in the last 2 decades, said Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica.

The 2015 American College of Rheumatology Workforce Study concluded that the demand for adult rheumatology services already outstripped the supply by 12.9% in 2015. And as current rheumatologists retire in tandem with a growing aged general population saddled with an accompanying burgeoning prevalence of rheumatic and musculoskeletal diseases, demand is expected to exceed supply by a whopping 102% in 2030.

The Workforce Study also highlighted the geographic maldistribution problem, with 21% of all adult rheumatologists now practicing in the Northeast and only 3.9% in the Southwest. Rheumatologists are also few and far between across large swaths of the South Central, North Central, and Northwest United States.

Today rheumatologists spend about half their working hours seeing patients with rheumatic diseases, one-quarter of their time in administrative tasks, 20% seeing patients with nonrheumatic diseases such as osteoarthritis, and the rest in teaching or research. It could be argued that, if rheumatologists declined to see patients with osteoarthritis, a nonrheumatic disease, it would put a sizeable dent in the workforce shortage, but it’s clear that nonrheumatologists can’t reliably differentiate inflammatory from noninflammatory arthritis. And there’s another problem with the idea of rheumatologists barring the office door to patients with nonrheumatic diseases: imagine a young clinical rheumatologist going out into practice and trying to tell referring internists, family physicians, and orthopedists that he or she doesn’t want to see patients with osteoarthritis, noninflammatory back pain, or fibromyalgia.

“How busy do you think you’re going to be, ever, if you tell the referring docs that you’re not going to see patients they think they need help with? And who’s going to make the correct diagnosis if we don’t at least see these patients initially?” Dr. Troum asked.

The case for sub-subspecialization: Martin J. Bergman, MD

Think about how many patients you’re treating for vasculitis, systemic lupus erythematosus, Behçet’s disease, or systemic sclerosis. Do you think you’re doing the best job that’s possible when you’re seeing just a handful of these patients, or would outcomes be better if they were seen at centers where the focus is specifically on these somewhat rare diseases? asked Martin J. Bergman, MD, a rheumatologist at Drexel University, Philadelphia, and in private practice in Ridley Park, Pa.

Bruce Jancin/MDedge News

We can take a lesson from other specialties. It’s well-documented that higher surgical volume brings better care and better outcomes for cardiovascular and cancer surgery. Specialized high-level trauma centers achieve 20%-30% better outcomes. And outcomes are also improved when joint replacement surgery is done at specialty centers. Why would we expect rheumatology to be any different?

Actually, there is already evidence from within our own field to support this concept. A longitudinal study of 150 consecutive SLE patients – half treated at the general rheumatology clinic at Rush University, Chicago, and the other half at the medical center’s specialized lupus clinic – showed demonstrably better quality-of-care outcomes for the patients seen in the dedicated lupus clinic. They were roughly twice as likely to undergo antiphospholipid antibody testing and were also significantly more likely to have bone mineral density testing, pneumococcal vaccination, and sunscreen counseling.

Look, I get it. This is not going to be possible everywhere. In underserved geographic areas, it may not be feasible. But I would think that, even in places where you can’t have sub-subspecialty clinics, maybe it’s time for rheumatologists to start thinking in terms of sub-specializing their own practice and getting out of areas where we can make little or no impact beyond what other physicians can accomplish. Most of us provide very little value for patients with fibromyalgia and chronic fatigue syndrome. We have only so much time, and rather than taking care of anybody who has an ache or a pain we should focus on where we can make the most impact, and that’s inflammatory disease.

The speakers reported having no financial conflicts regarding their presentations.

bjancin@mdedge.com

Sub-subspecialization would be counterproductive: Orrin M. Troum, MD

The much-discussed looming rheumatology workforce shortage is actually here already. And it’s going to worsen rapidly. Add to that the striking geographic maldistribution of rheumatologists across the United States, and it makes little sense for some rheumatologists to declare they’re only going to see patients with psoriatic arthritis, or gout, or lupus. Such sub-subspecialization will only worsen the workforce problem, Orrin M. Troum, MD, asserted at the 2021 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Besides, surveys indicate that most rheumatologists like what they do now, despite their status as the lowest-paid subspecialists within internal medicine. They enjoy a sense of satisfaction stemming from their ability to help patients with chronic debilitating diseases turn their lives around as a result of revolutionary treatment advances in the last 2 decades, said Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica.

The 2015 American College of Rheumatology Workforce Study concluded that the demand for adult rheumatology services already outstripped the supply by 12.9% in 2015. And as current rheumatologists retire in tandem with a growing aged general population saddled with an accompanying burgeoning prevalence of rheumatic and musculoskeletal diseases, demand is expected to exceed supply by a whopping 102% in 2030.

The Workforce Study also highlighted the geographic maldistribution problem, with 21% of all adult rheumatologists now practicing in the Northeast and only 3.9% in the Southwest. Rheumatologists are also few and far between across large swaths of the South Central, North Central, and Northwest United States.

Today rheumatologists spend about half their working hours seeing patients with rheumatic diseases, one-quarter of their time in administrative tasks, 20% seeing patients with nonrheumatic diseases such as osteoarthritis, and the rest in teaching or research. It could be argued that, if rheumatologists declined to see patients with osteoarthritis, a nonrheumatic disease, it would put a sizeable dent in the workforce shortage, but it’s clear that nonrheumatologists can’t reliably differentiate inflammatory from noninflammatory arthritis. And there’s another problem with the idea of rheumatologists barring the office door to patients with nonrheumatic diseases: imagine a young clinical rheumatologist going out into practice and trying to tell referring internists, family physicians, and orthopedists that he or she doesn’t want to see patients with osteoarthritis, noninflammatory back pain, or fibromyalgia.

“How busy do you think you’re going to be, ever, if you tell the referring docs that you’re not going to see patients they think they need help with? And who’s going to make the correct diagnosis if we don’t at least see these patients initially?” Dr. Troum asked.

The case for sub-subspecialization: Martin J. Bergman, MD

Think about how many patients you’re treating for vasculitis, systemic lupus erythematosus, Behçet’s disease, or systemic sclerosis. Do you think you’re doing the best job that’s possible when you’re seeing just a handful of these patients, or would outcomes be better if they were seen at centers where the focus is specifically on these somewhat rare diseases? asked Martin J. Bergman, MD, a rheumatologist at Drexel University, Philadelphia, and in private practice in Ridley Park, Pa.

Bruce Jancin/MDedge News

We can take a lesson from other specialties. It’s well-documented that higher surgical volume brings better care and better outcomes for cardiovascular and cancer surgery. Specialized high-level trauma centers achieve 20%-30% better outcomes. And outcomes are also improved when joint replacement surgery is done at specialty centers. Why would we expect rheumatology to be any different?

Actually, there is already evidence from within our own field to support this concept. A longitudinal study of 150 consecutive SLE patients – half treated at the general rheumatology clinic at Rush University, Chicago, and the other half at the medical center’s specialized lupus clinic – showed demonstrably better quality-of-care outcomes for the patients seen in the dedicated lupus clinic. They were roughly twice as likely to undergo antiphospholipid antibody testing and were also significantly more likely to have bone mineral density testing, pneumococcal vaccination, and sunscreen counseling.

Look, I get it. This is not going to be possible everywhere. In underserved geographic areas, it may not be feasible. But I would think that, even in places where you can’t have sub-subspecialty clinics, maybe it’s time for rheumatologists to start thinking in terms of sub-specializing their own practice and getting out of areas where we can make little or no impact beyond what other physicians can accomplish. Most of us provide very little value for patients with fibromyalgia and chronic fatigue syndrome. We have only so much time, and rather than taking care of anybody who has an ache or a pain we should focus on where we can make the most impact, and that’s inflammatory disease.

The speakers reported having no financial conflicts regarding their presentations.

bjancin@mdedge.com

Sub-subspecialization would be counterproductive: Orrin M. Troum, MD

The much-discussed looming rheumatology workforce shortage is actually here already. And it’s going to worsen rapidly. Add to that the striking geographic maldistribution of rheumatologists across the United States, and it makes little sense for some rheumatologists to declare they’re only going to see patients with psoriatic arthritis, or gout, or lupus. Such sub-subspecialization will only worsen the workforce problem, Orrin M. Troum, MD, asserted at the 2021 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

Besides, surveys indicate that most rheumatologists like what they do now, despite their status as the lowest-paid subspecialists within internal medicine. They enjoy a sense of satisfaction stemming from their ability to help patients with chronic debilitating diseases turn their lives around as a result of revolutionary treatment advances in the last 2 decades, said Dr. Troum, a rheumatologist at the University of Southern California, Los Angeles, and in private practice in Santa Monica.

The 2015 American College of Rheumatology Workforce Study concluded that the demand for adult rheumatology services already outstripped the supply by 12.9% in 2015. And as current rheumatologists retire in tandem with a growing aged general population saddled with an accompanying burgeoning prevalence of rheumatic and musculoskeletal diseases, demand is expected to exceed supply by a whopping 102% in 2030.

The Workforce Study also highlighted the geographic maldistribution problem, with 21% of all adult rheumatologists now practicing in the Northeast and only 3.9% in the Southwest. Rheumatologists are also few and far between across large swaths of the South Central, North Central, and Northwest United States.

Today rheumatologists spend about half their working hours seeing patients with rheumatic diseases, one-quarter of their time in administrative tasks, 20% seeing patients with nonrheumatic diseases such as osteoarthritis, and the rest in teaching or research. It could be argued that, if rheumatologists declined to see patients with osteoarthritis, a nonrheumatic disease, it would put a sizeable dent in the workforce shortage, but it’s clear that nonrheumatologists can’t reliably differentiate inflammatory from noninflammatory arthritis. And there’s another problem with the idea of rheumatologists barring the office door to patients with nonrheumatic diseases: imagine a young clinical rheumatologist going out into practice and trying to tell referring internists, family physicians, and orthopedists that he or she doesn’t want to see patients with osteoarthritis, noninflammatory back pain, or fibromyalgia.

“How busy do you think you’re going to be, ever, if you tell the referring docs that you’re not going to see patients they think they need help with? And who’s going to make the correct diagnosis if we don’t at least see these patients initially?” Dr. Troum asked.

The case for sub-subspecialization: Martin J. Bergman, MD

Think about how many patients you’re treating for vasculitis, systemic lupus erythematosus, Behçet’s disease, or systemic sclerosis. Do you think you’re doing the best job that’s possible when you’re seeing just a handful of these patients, or would outcomes be better if they were seen at centers where the focus is specifically on these somewhat rare diseases? asked Martin J. Bergman, MD, a rheumatologist at Drexel University, Philadelphia, and in private practice in Ridley Park, Pa.

Bruce Jancin/MDedge News

We can take a lesson from other specialties. It’s well-documented that higher surgical volume brings better care and better outcomes for cardiovascular and cancer surgery. Specialized high-level trauma centers achieve 20%-30% better outcomes. And outcomes are also improved when joint replacement surgery is done at specialty centers. Why would we expect rheumatology to be any different?

Actually, there is already evidence from within our own field to support this concept. A longitudinal study of 150 consecutive SLE patients – half treated at the general rheumatology clinic at Rush University, Chicago, and the other half at the medical center’s specialized lupus clinic – showed demonstrably better quality-of-care outcomes for the patients seen in the dedicated lupus clinic. They were roughly twice as likely to undergo antiphospholipid antibody testing and were also significantly more likely to have bone mineral density testing, pneumococcal vaccination, and sunscreen counseling.

Look, I get it. This is not going to be possible everywhere. In underserved geographic areas, it may not be feasible. But I would think that, even in places where you can’t have sub-subspecialty clinics, maybe it’s time for rheumatologists to start thinking in terms of sub-specializing their own practice and getting out of areas where we can make little or no impact beyond what other physicians can accomplish. Most of us provide very little value for patients with fibromyalgia and chronic fatigue syndrome. We have only so much time, and rather than taking care of anybody who has an ache or a pain we should focus on where we can make the most impact, and that’s inflammatory disease.

The speakers reported having no financial conflicts regarding their presentations.

bjancin@mdedge.com

Most checkpoint inhibitor–induced rheumatic complications in cancer patients can be treated successfully with corticosteroids, albeit often at considerably higher doses than rheumatologists typically use in managing rheumatoid arthritis, Eric M. Ruderman, MD, observed at the 2021 Rheumatology Winter Clinical Symposium.

“In RA, we’re all used to the idea that 5 or 10 mg of corticosteroids per day can make a tremendous difference. That’s not always the case here. Patients who develop rheumatic immunotherapy-related adverse events often require 20-30 mg/day to get symptoms under control,” according to Dr. Ruderman, professor of medicine (rheumatology) at Northwestern University, Chicago.

This may be in part because oncologists typically don’t refer affected patients to rheumatologists early on. Guidelines from the National Comprehensive Cancer Network and other oncology groups suggest referral only once a patient develops grade 3 immunotherapy-related rheumatic adverse events, meaning the symptoms significantly impair daily activities, he explained.

Checkpoint inhibitors, which induce T-cell activation to fight the patient’s malignancy, can produce a plethora of off-target effects. These adverse events may involve the skin, heart, lungs, kidneys, eyes, blood, GI tract, and endocrine organs. The drugs also can cause rheumatic or neurologic complications. The most common of these adverse events are colitis and rash. Next most common are arthritis and arthralgia. Rheumatic side effects are most common as a consequence of immunotherapy using a CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor, but can also occur in association with programmed cell death protein 1 (PD-1) inhibitors and PD-ligand 1 inhibitors. Arthritis and other rheumatic adverse events are more common in patients undergoing combination therapy.

Some form of frank inflammatory arthritis occurs in 5%-10% of cancer patients undergoing checkpoint inhibitor therapy. This can manifest as an RA-like polyarthritis, spondyloarthritis, polymyalgia rheumatica, necrotizing myositis, or vasculitis. Arthralgia occurs in up to 40% of treated patients.

This immunotherapy-related arthritis is typically more inflammatory than RA. It also has a much more abrupt onset. It is usually seronegative and has no gender predisposition, and the limited available evidence to date suggests there is no increased risk of this complication in checkpoint inhibitor–treated patients with a history of prior rheumatic disease, according to Dr. Ruderman.
 

Delayed onset and resolution of rheumatologic immune-related adverse events

“Onset and resolution of rheumatologic adverse events with immunotherapy may be delayed. This is an important point: While skin rash and colitis often show up pretty early in the course of immunotherapy, some of the arthritic events can happen later. They can actually continue after the immunotherapy is stopped,” the rheumatologist said.

Indeed, a retrospective nationwide Canadian study of 117 patients at nine academic centers who developed 136 rheumatic immune-related adverse events in conjunction with cancer immunotherapy found that the mean time to the first such event was 6.8 months into checkpoint inhibitor therapy. The most common rheumatic complication was symmetric polyarthritis, affecting 45 patients. Other rheumatologic immune-related complications included polymyalgia rheumatica in 17 patients, noninflammatory musculoskeletal symptoms in 18, and myositis in 9.

Seventy-six patients were treated with prednisone for a mean of 8.4 months at a maximum dose of 60 mg/day. Forty-two moved up the treatment ladder to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to manage their symptoms. Only two patients required escalation to biologic therapy. A reassuring finding in this relatively small study was that treatment of the patients’ rheumatic complications didn’t appear to worsen the tumor response to immunotherapy: Twenty-three patients experienced tumor progression prior to treatment of their rheumatic disorder, and 14 did so following treatment.
 

Flares of preexisting rheumatic diseases

These tend to occur much earlier in the course of immune checkpoint inhibitor therapy for cancer than de novo immunotherapy-related rheumatic adverse events. In a retrospective Australian study of 12 cancer patients with preexisting rheumatic disease before going on a PD-1 inhibitor and 24 others with no such history, all of whom developed rheumatic adverse events while on the checkpoint inhibitor, the mean time to a flare of preexisting rheumatic disease was 6.2 weeks, compared to 21.5 weeks in patients who experienced a de novo rheumatic adverse event.

Dr. Ruderman supports recommendations from the European Alliance of Associations for Rheumatology (EULAR) for the management of rheumatic immune-related adverse events due to cancer immunotherapy, even though the underlying level of evidence is fairly weak. The recommendations call for the use of csDMARDs when corticosteroids don’t adequately control symptoms. And when the response to csDMARDs is insufficient, the next step is a biologic, preferably a tumor necrosis factor inhibitor or interleukin-6 inhibitor.

“At our institution, the oncologists are a little bit nervous about using biologics in cancer patients, but I think more and more they’re going to have to accept it. And so far there isn’t a ton of evidence that suggests the addition of biologics interferes with the efficacy of the immunotherapy,” the rheumatologist said.

He underscored the critical importance of one of the overarching principles of the EULAR guidelines: the need for interdisciplinary coordination between rheumatologists and oncologists regarding the problem of rheumatologic immune-related adverse events.

“Oncologists aren’t good at managing inflammatory arthritis. I think they really need us,” he said.

Dr. Ruderman reported serving as a consultant to and/or receiving a research grant from nine pharmaceutical companies.

bjancin@mdedge.com

Most checkpoint inhibitor–induced rheumatic complications in cancer patients can be treated successfully with corticosteroids, albeit often at considerably higher doses than rheumatologists typically use in managing rheumatoid arthritis, Eric M. Ruderman, MD, observed at the 2021 Rheumatology Winter Clinical Symposium.