This presentation explores the impact of COVID-19 on individuals with psoriasis, focusing on data collected through the international registries, SECURE-Psoriasis (so protect) and the patient self-reporting companion registry, so protect me. Psoriasis is a common immune-mediated inflammatory disease where patients often require immunosuppressive treatments, raising concerns about COVID-19 susceptibility and outcomes due to altered immune responses. The presenter discusses how the pandemic has posed challenges, both directly through infection risks and indirectly via mental health impacts and treatment adherence.
Over 18 months, clinicians reported 1,205 COVID-19 cases involving psoriasis patients via the so protect registry, and more than 4,700 patients self-reported their experiences through so protect me across multiple countries. Analysis showed that the risk factors for severe COVID-19 outcomes in psoriasis patients mirrored the general population: older age, male sex, non-white ethnicity, and comorbidities like hypertension, liver disease, and cardiovascular conditions were associated with increased hospitalization risk.
COVID-19 has led to significant global mortality and morbidity, with over 220 million diagnosed cases and more than 4.5 million reported deaths worldwide. For patients with psoriasis, a common immune-mediated inflammatory disease, the pandemic presented numerous uncertainties and challenges.
Firstly, there are potentially overlapping immune pathways at play in both psoriasis and COVID-19, and we’ve already heard about Type 1 interferons. It’s been unclear how this overlap might affect the risk of infection or severe outcomes.
Secondly, multi-morbidity is highly prevalent in the psoriasis patient population. A large study published early in the pandemic, using data from 17 million adults in the general population, highlighted the impact of long-term health conditions on COVID-19-related deaths. This study identified increased age, male sex, and non-white ethnicity as risk factors for poor outcomes, in addition to several long-term health conditions already known to be more prevalent in psoriasis, such as obesity, chronic liver disease, and heart disease. It also collectively identified rheumatoid arthritis, lupus, and psoriasis as potential risk factors for COVID-19-related death. However, the specific risk attributed to psoriasis alone or to the treatments used for psoriasis remained uncertain.
Thirdly, there’s the issue of indirect excess morbidity, which has emerged as a key concern as the pandemic has progressed. For example, increased risks of anxiety and depression have been reported in the general population during the pandemic, along with documented shortfalls in the care of common long-term conditions. Our patients with psoriasis may be particularly vulnerable to indirect excess morbidity due to already prevalent mental health conditions, the need for regular follow-up for multi-morbidities, and immunosuppressant drug monitoring.
Finally, and importantly, is the issue of immunosuppressants. There’s been concern and uncertainty about the impact of these medications in the context of COVID-19. We know these medications affect the immune system and are associated with higher risks of infections generally. Therefore, there was concern that immunosuppressants might adversely impact outcomes by suppressing the body’s antiviral immune response, enabling uncontrolled viral replication and dissemination early in infection. This is the bimodal model discussed earlier. Conversely, many damaging effects of late-stage COVID-19 are related to a hyperinflammatory host immune response, so these treatments might, in fact, have a protective effect against adverse outcomes in late-stage disease.
To better understand the impact of COVID-19 and the pandemic on people with psoriasis, address these unanswered questions, and inform immediate priorities for clinical care, we launched the PsoProtect registry in March of last year, right at the beginning of the pandemic. It’s a global registry for clinicians to report outcomes of COVID-19 in individuals with psoriasis. Cases are submitted online via the PsoProtect website by clicking on the red icon, which opens a simple online case report form that takes 5 to 10 minutes to complete. Please continue to submit your cases as you see them.
We also launched PsoProtect Me, a companion global registry for individuals with psoriasis to self-report their experiences of the pandemic, whether or not they’ve had COVID-19. We aligned the questions closely with PsoProtect but were able to ask additional questions on patients’ risk-mitigating behaviors, particularly shielding (an umbrella term encompassing quarantine, distancing within the home, or self-isolation). We embedded validated screening tools for depression and anxiety within PsoProtect Me, and more recently, we’ve updated it to include vaccination uptake questions. The PsoProtect Me website allows patients to self-report and is now available in nine different languages, thanks to the fantastic support from all our partner professional and patient organizations, including the IPC.
Both PsoProtect and PsoProtect Me have truly been global efforts. We also have partner registries running aligned efforts in different disease populations, which has opened up avenues for cross-disease comparisons, which we’ll touch on later.
Here’s the data we’ve collected: In PsoProtect, just over 1,200 clinicians have reported their COVID-19 cases in psoriasis patients, showing a global spread. In PsoProtect Me, more than 4,700 people with psoriasis have completed the survey, with worldwide contributions across Europe, South America, and North America.
Now, onto the analysis. The first paper we published last year looked at factors associated with adverse COVID-19 outcomes in patients with psoriasis, using data from 374 cases—the first cases submitted to PsoProtect by clinicians. We’ve since updated the analysis, and the data I’ll be presenting today is from our updated dataset of 1,205 patients.
The first and most important thing to say is that of all the cases reported to PsoProtect, over 90% of patients fully recovered from COVID-19. This is in the context that most patients reported to PsoProtect were on an immunosuppressant—a drug that affects the immune system. The vast majority (70%) were on biologics, with 17% on non-biologics. This headline finding is already reassuring.
We then looked at risk factors for hospitalization due to COVID-19 and found very similar patterns to those observed in the general population. The risk factors in psoriasis are similarly male sex, older age, non-white ethnicity, and comorbidities, including hypertension, chronic liver disease, chronic lung disease, and cardiovascular disease.
Regarding drug-specific risk factors, we found that hospitalization for COVID-19 was associated with non-biologic immunosuppressants compared with biologics. In other words, the use of biologics was associated with a reduced risk of hospitalization. This finding is consistent with data from several case series and global registry data in rheumatology from the Global Rheumatology Alliance and in IBD from the Secure-IBD registry.
In fact, we collaborated with these two other global registries and contributed to a pooled cross-disease analysis of just over 6,000 patients from 74 countries. This analysis showed that compared with TNF inhibitor monotherapy (which was the most frequent biologic in the registry), there was a higher odds of hospitalization or death with azathioprine or 6-MP monotherapy, or methotrexate monotherapy, and also with TNF inhibitors in combination with azathioprine, and with JAK inhibitors. As we’ve touched on earlier, JAK inhibitor use prior to infection was associated with a worse outcome. This may be consistent with the known effect of this class of medications on reducing the innate immune response and Type 1 interferon, leading to impaired viral clearance.
It’s important to consider the limitations when looking at this registry-level data. These observations are not causal, and other unmeasured factors may be associated with biologic use. Specifically, we explored risk-mitigating behaviors, and I’ll come to that shortly. There’s also selection bias at play; the registry is dominated by patients taking biologics, with relatively fewer patients reported on non-biologics. Clinicians may also be more likely to report severe COVID-19 cases. There’s no denominator data, so we can’t ascertain the incidence of COVID-19 in those receiving particular treatments, and there’s no general population data in PsoProtect, so we can’t directly compare with the general population. Of course, with these studies, we’re always limited by the size of the dataset, which is relatively small compared to the global scale of COVID-19.
However, we did go on to look at risk-mitigating behaviors using the PsoProtect Me registry, directly asking patients about their actions to mitigate risk during the pandemic. We performed a pooled analysis with COVID-19 in Rheumatology (CoRe-UK), a similar patient-reported registry in rheumatology, involving 3,720 participants. The analysis showed that shielding was more common in patients receiving biologics compared to those receiving standard systemics or no systemic therapy. This greater risk-mitigating behavior among those on biologics may be contributing to the signal of lower risk of adverse COVID-19 outcomes observed in the clinician-reported datasets, and certainly, risk-mitigating behavior is an unmeasured confounder in the clinician-reported data.
Finally, we looked at the burden of the pandemic in people with psoriasis, asking about changes in patients’ psoriasis during the pandemic. 43% of patients reporting to PsoProtect Me stated that their psoriasis had worsened during the pandemic. Self-reported worsening of psoriasis was associated with anxiety or depression. We embedded the GAD-2 and PHQ-2 in PsoProtect Me to collect this data, and it appears that females are disproportionately affected, as shown in the multivariable logistic regression analysis.
18% of patients in PsoProtect Me reported non-adherence to their immunosuppressant systemic therapy, overwhelmingly due to concerns regarding complications from COVID-19. Non-adherence was associated with worsening psoriasis, and a positive mental health screen was more common in those reporting non-adherence compared to those who remained adherent to their treatment.
To summarize all our findings, we’ve seen that the majority of patients reported to PsoProtect who are taking drugs that affect the immune system fully recovered from COVID-19. The data indicates that biologic monotherapy use in this cohort is associated with a reduced risk of hospitalization. We’ve seen similar risk factors to the general population: older age, male sex, and non-white ethnicity are associated with a greater risk of COVID-19 hospitalization in people with psoriasis. Comorbidities such as hypertension and chronic liver disease were more common in those who were hospitalized. Worsening psoriasis is common during the pandemic and is associated with poor mental health. Non-adherence is associated with worsening psoriasis, primarily driven by concerns over immunosuppressant-related risks of COVID-19.
This last observation is particularly important because guidelines published during the pandemic, such as the NPF Task Force guideline, recommend continuing immunosuppression in people without COVID-19 to maintain disease control. These recommendations are, of course, based on data emerging from registries like ours. Similarly, the IPC also underscored this through their IPC statement on COVID-19 and psoriasis, which came out last year.
The data truly underscore the importance of holistic models of care and preserving access to psychological support. As clinicians, we should consider non-adherence in those with worsening disease and continue to communicate about medication-related COVID-19 risks, hoping to mitigate a long-lasting detrimental impact of the pandemic on health outcomes.
Throughout these challenging 18 months, we’ve been keen to provide real-time data feedback to our community—scientists, clinicians, patients, and the public. We’ve done so through our current data pages, which you can see here, a snapshot from our PsoProtect website and the PsoProtect Me website. We’ve also summarized our findings as infographics, which we’ve shared through social media and all our partner patient organizations.
I’d like to end by sincerely thanking and acknowledging the huge team effort that has gone into PsoProtect and PsoProtect Me. It’s been an absolute pleasure to work with everyone listed here, and it’s great to have such international engagement. I’d like to acknowledge the other members of the executive committee: Catherine Smith, Jonathan Barker, and Chris Griffiths. And of course, a huge thank you to all our partner professional organizations, including the IPC, and partner patient organizations, who have truly helped to encourage participation and disseminate the findings. Thank you very much.
Thank you, Dr. Mario, for that great talk. We have some questions in the question and answer chat box. I have one: Are you looking at vaccinations? Are you doing a registry around that?
Yes, that’s obviously a really important question, and it follows nicely from the data. Separate from PsoProtect, we at St. John’s have been leading research into the immunogenicity of vaccines in the context of immunosuppression. We released the first-dose data, published in The Lancet Rheumatology, and we’re currently looking at the second-dose data. It’s interesting; the first-dose data showed that the cellular immunogenicity—we looked at Th1 and T follicular helper cell responses and IL-17 responses—to that first dose were comparable in the cohort of patients we had receiving biologics and those on methotrexate. However, the functional humoral responses and serological responses seemed to be lower in patients on methotrexate compared to biologics. The second-dose data will be very interesting to see more of.
Do you think patients on systemics are going to be more likely to get the vaccine, or not? Is that something you’re collecting also?
It’s been interesting. We’ve just had a look because we updated the questionnaire earlier this year to ask about vaccination uptake. And actually, from PsoProtect Me, it’s been overwhelmingly very positive in that patients who are on immunosuppressants are getting them; they’re keen to have the vaccine. Very few have said that they’re not. So, I think that’s probably testament to the communication going on through clinicians and hospitals, really encouraging patients to take it up. But it’s been overwhelmingly very positive, actually, and that’s great.