Clinical Consultations™: Finding Opportunities to Improve the Management of Patients with Connective Tissue Disease-associated Pulmonary Arterial Hypertension (CTD-PAH)

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Read the most up-to-date information about the latest developments in psoriatic arthritis

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Expert Perspective on the Management of Psoriatic Arthritis

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Patrick Campbell is the assistant managing editor of Rheumatology Network, as well as its sister publications Practical Cardiology and Endocrinology Network. Prior to joining these brands, he led coverage of cardiology and diabetes with HCPLive. Before joining parent company MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA, and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a freelance multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

New research from a team at the Karolinska Institutet suggests media coverage of studies examining cannabis use as a method for alleviating chronic pain are the recipients of a significant level of positive media coverage, regardless of results.

A systematic review and meta-analysis of 20 studies examining cannabinoids with a double-blind, placebo-controlled design, results of the study demonstrate that although the reductions in pain intensity observed in these studies was significant, media attention of these trials was described as “proportionally high”, with a strong positive bias and no associations observed with clinical outcomes.

“We see that cannabis studies are often described in positive terms in the media regardless of their results,” said lead investigator Filip Gedin, PhD, a postdoctoral researcher at the Department of Clinical Neuroscience, Karolinska Institutet, 

. “This is problematic and can influence expectations when it comes to the effects of cannabis therapy on pain. The greater the benefit a treatment is assumed to have, the more potential harms can be tolerated.”

As the decades have gone by since California introduced medical cannabis to the United States, now the majority of states have passed legislation allowing for recreational use. In addition to medically-prescribed cannabis, the popularity of CBD-based products among consumers has also undergone an explosion in recent years. This, combined with growing opioid epidemic, has led to medical cannabis being purported as a panacea of sorts when receiving interest and coverage from large media outlets.

The current research endeavor was led by Gedin and a team of colleagues with the intent of estimating the size of placebo responses in randomize clinical trials comparing cannabinoids to placebo therapy in treatment of pain and whether the magnitude of response was associated with media attention these studies received. With this in mind, investigators designed their study as a systematic review and meta-analysis of data published within the MEDLINE and Embase databases form inception through September 2021.

Limiting their analyses to studies with a double-blind, placebo-controlled design and adult patient populations with clinical pain of any duration, investigators identified 20 studies for inclusion. The investigators’ initial search yielded 922 individual records. Of these, investigators determined 53 met inclusion criteria. From this group, 33 were excluded due to insufficient data for calculating effect size, leaving 20 articles for inclusion in the meta-analysis. These 20 studies included 1459 individuals. This cohort had a mean age of 51 (SD, 7) years, with an age range of 39-62 years, and 56% were female.

For the purpose of analysis, change in pain intensity from before to after treatment, which was measured as bias-corrected standardized mean differences (Hedges 

), served as the primary outcome of interest for the study. Investigators pointed out a randomized-effects model was used for pool data and creating effect estimates.

Results of the investigators’ analyses demonstrated pain intensity observed in these studies was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges 

 <.001). Further analysis demonstrated trials with low risk of bias had greater placebo responses (

=.02). Results also suggested they count of media attention and level of dissemination associated with each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes observed in the studies.

“The findings of this systematic review and meta-analysis suggest that placebo responses contribute significantly to pain reduction in cannabinoid clinical trials," wrote investigators. "The unusually high media attention surrounding cannabinoid trials, with positive reports irrespective of scientific results, may uphold high expectations and shape placebo responses in future trials. This influence may impact the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief."

Placebo Response and media attention in randomized clinical trials assessing cannabis-based therapies for pain: A systematic review and meta-analysis

Articles

A systematic review and meta-analysis assessing more than a dozen double-blind, placebo-controlled trials evaluating cannabis-based products for pain relief suggest these studies were the recipient of a disproportionate level of media coverage that was not associated with the results of each study. 

Trials Examining Cannabis for Pain Relief Receive Disproportionate Media Coverage, Regardless of Results

Katie Robinson is a medical writer. She covers various health and medical topics for a professional audience.

In patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA), withholding methotrexate for 2 weeks after vaccination with ChAdOx1 nCov-19 (AstraZeneca) for COVID-19 led to a higher antibody response compared with the continuation of methotrexate, although this was accompanied by an increased risk of disease flare. This is according to research published in 

 which found withholding methotrexate only after the second vaccine dose may carry a lower risk for disease flare, with no considerable difference in the antibody response.

“This finding remained despite the wide gap between the 2 doses of the ChAdOX1 n COV-19 vaccine (12–16 weeks) and could be translated into practice by withholding methotrexate only during the second dose of vaccine to achieve an optimal trade-off between immunogenicity and risk of flare,” Padmanabha Shenoy, DM, of the Centre for Arthritis and Rheumatism in Cochin, India, and colleagues, noted.

An optimal COVID-19 vaccination strategy is essential for vulnerable population groups, including people with autoimmune inflammatory arthritis on immunosuppressants such as methotrexate, which inhibit vaccine-induced immunity against SARS-CoV-2. However, the evidence supporting methotrexate withdrawal at the time of COVID-19 vaccination is scarce, especially for the ChAdOx1 nCoV-19 vaccine.

Between July 6 and December 15, 2021, participants were recruited to 2 parallel, randomized trials, dubbed MIVAC I and MIVAC II. Researchers assessed the post-vaccination antibody titers and disease flare rates that resulted from withholding methotrexate for 2 weeks after each dose of the ChAdOx1 nCov-19 vaccine (MIVAC I) or only after the second dose of vaccine (MIVAC II) compared with continuation of methotrexate. The trials, which were undertaken at a single center in India, included people with either PsA or RA with stable disease activity, who had been on a fixed dose of methotrexate for the preceding 6 weeks. People with previous COVID-19 or who were positive for anti-SARS-CoV-2 nucleocapsid antibodies were excluded, as were those on high-dose corticosteroids and rituximab. The primary outcome for both trials was the titer of anti-receptor binding domain (RBD) antibody measured 4 weeks after the second vaccine dose.

In MIVAC I, a total of 158 participants (94% women) completed the study. The median post-vaccination antibody titers in the methotrexate hold group (n=80, 14% PsA) were significantly higher compared with the control group (n=78, 8% PsA) (2484.0 IU/mL, IQR 1050.0–4388.8 

 1147.5 IU/mL, 433.5–2360.3; p=0.0014). Meanwhile, 25% of the methotrexate hold group and 8% of the methotrexate continuation group had a disease flare after the first vaccine dose (p=0.0050). After the second vaccine dose, the respective rates were 24% and 13% (p=0.10).

In MIVAC II, a total of 157 participants (86% women) completed the study. The methotrexate hold group (n=76, 8% PsA) had higher post-vaccination antibody titers compared with the control group (n=81, 1% PsA) (2553.5 IU/ml, IQR 1792.5–4823.8 

 990.5, 356.1–2252.5; p<0.0001). However, no significant difference was found in the proportion of participants with a disease flare between the groups (12% of the methotrexate hold group vs 5% of the methotrexate continuation group; p=0.15).

No serious adverse events were reported during the trial period.

“Interruption of methotrexate during the second dose of ChAdOx1 nCov-19 vaccine appears to be a safe and effective strategy to improve the antibody response in patients with rheumatoid or psoriatic arthritis,” investigators concluded.

Skaria TG, Sreeprakash A, Umesh R, et al. 

Withholding methotrexate after vaccination with ChAdOx1 nCov19 in patients with rheumatoid or psoriatic arthritis in India (MIVAC I and II): results of two, parallel, assessor-masked, randomised controlled trials

. 2022;4(11):e755-e764. doi:10.1016/S2665-9913(22)00228-4

Holding methotrexate after the second COVID-19 vaccine dose is associated with similar immunogenicity and a lower risk of disease flare compared with withholding methotrexate after both vaccine doses.

Holding Methotrexate After Second COVID-19 Vaccine Dose May Be Best in Psoriatic, Rheumatoid Arthritis 

Lana Dykes is the Editor of Rheumatology Network. She is an experienced editor and technical writer with a demonstrated history of working in the banking and publishing industries. She enjoys cooking, yoga, and drawing. 

Symptom-Targeting Non-Pharmacological Approaches Individualize Fibromyalgia Treatment

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Early Gout Onset, Tophaceous Disease in Men Linked to Risk Alleles

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ACR 22 Convergence Preview, with Zsuzsanna McMahan, MD

Each year, the American College of Rheumatology (ACR) hosts an annual meeting that serves as one of the foremost opportunities for advancement and collaboration within the field of rheumatology. This year’s meeting, aptly named ACR 2022 Convergence, represents the first opportunity for many within the field to converge, collaborate, and celebrate the advances within the field together since 2019.

COVID-19 Negatively Impacts Physical Activity in Patients with Rheumatic Disease

Investigators aimed to assess self-reported changes in physical activity during the COVID-19 pandemic.

Inflammatory Arthritis: Trends, Risk Factors, and What Rheumatologists Need to Know

Rheumatology Network interviewed Bahar Moghaddam, MD, Assistant Professor of Medicine in the Division of Rheumatology, Mount Sinai Health System, to discuss the impact of arthritis in the United States and worldwide, recent drug approvals, and the importance of early diagnosis and management of rheumatic diseases. Refresh your knowledge of arthritis with this professional insight.

Take a few minutes to catch up on the latest rheumatology news for the month of November 2022. 

Rheumatology Network's November 2022 Recap

Rheumatology Network interviewed ­­­­­­­­­­ Benjamin Terrier, MD, PhD, to discuss his recent 

American College of Rheumatology Convergence 2022

 presentation "Innovative Anti-pneumococcal Vaccine Strategies versus Standard Vaccination Regimen in Patients with ANCA-associated Vasculitides Receiving Rituximab Therapy: A Multicenter Randomized Controlled Trial (PNEUMOVAS)." Terrier is Professor of Internal Medicine at Cochin Hospital in Paris, France.

As patients treated with glucocorticoids and rituximab co-therapy have been shown to be at a higher risk of infection, particularly pneumococcal infections, and vaccine responses in these patients are especially impaired, investigators attempted to develop vaccine strategies to increase immune response in this patient population.

“We always try to improve the prevention of infection, and we only have very few tools that allow us to improve that,” Terrier explained. “It was shown by many different studies, especially in rheumatoid arthritis, that the treatment, and especially the B cell depletion agent, rituximab, which is the most frequent treatment used in this type of disease, was responsible for a lack of efficacy of the vaccine.”

In the multicenter, randomized, phase 2 trial, investigators enrolled patients with ANCA-associated vasculitides (AAV), who are often treated with rituximab. They then compared the standard of care treatment with 2 innovative “reinformed” anti-pneumococcal vaccine strategies, with the primary outcome being clinical response via blood test.

Results indicated that vaccine response with the standard regimen dramatically low; however, both novel strategies were able to significantly improve response.

“I think it opens the way for reinforced vaccination strategy for all vaccines,” Terrier hypothesized. “For instance, during the COVID-19 pandemic, in fact, the vaccine was reinjected more frequently, but there was never a question of increasing the dose at each vaccine. We are mainly focused on trying to define the most important medical needs and to trying to improve that, but I think it was something quite important as a proof of concept in all the vaccine trials in the field of these patients.”

Videos

Benjamin Terrier, MD, PhD: Improving Vaccine Response in Patients Receiving Rituximab 

Rheumatology Network interviewed ­­­­­­­­­­ Amy Mudano, MPH to discuss her recent 

 presentation "COVID-19 Vaccine Uptake and Reasons for Hesitancy in a Large Rheumatology Practice Network." Mudano is Senior Epidemiologist at Bendcare and a research partner with CreakyJoints.

The Bendcare organization, comprised of over 100 rheumatologists, employs a modifiable and customizable survey to glean information on the 250,000 patients registered within the network.

Mudano and her team used this survey to garner more information on COVID-19 vaccination, including if patients had gotten the vaccine, the number of doses and/or booster shots they had received, and if they had not been vaccinated, what had prevented them from doing so.

The survey, which is ongoing, provided some surprising results.

“The patients who had yet to get any vaccine cited mostly worries about safety issues and worries about long term safety effects,” Mudano explained. “They didn't feel that they'd had enough time or that there had been enough time to see if the vaccine was going to be safe or not. Those were the primary reasons for those patients once they had received the vaccine.

“If they had any hesitancy about receiving additional shots, the main reason they gave for not wanting to do that was because their doctor had not told them to do it yet. We thought that was a very interesting result and something that we could point out to our physicians and say, ‘Here's an action that you can take. You can tell your patients if you think they need a booster shot, they're just waiting for you to tell them that they should go ahead and get it.’”

Mudano stresses the importance of educating patients in increase vaccine uptake and reduce hesitancy.

“These are people with autoimmune conditions who are taking immunomodulatory drugs that affect their immune system,” Mudano emphasized. “It's been shown that they may have worse outcomes if they do get COVID. So, it's important that they know that they really need this vaccine.”

Amy Mudano, MPH: Increasing COVID-19 Vaccine Uptake in Patients with Rheumatic Disease

Rheumatology Network interviewed Robert Maughan, PhD, to discuss his recent 

 presentation “Evaluating the Safety and Factors Associated with Treatment Cessation in Takayasu Arteritis.” Maughan, who is associated with Imperial College London, explains the findings of the exploratory analysis, the potential for predictability in the disease course, and how they may be able to reduce the incidence rates of some of the adverse effects associated with treatment.

Why did your team decide to evaluate the safety of treatment cessation in this patient population?

In Takayasu Arteritis, the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR) have recently introduced guidelines for initial treatment, but there really is little or no data available to guide decisions for what happens afterwards in terms of whether treatment cessation is safe or feasible. So, we wanted to consider the full patient pathway and give patients and clinicians an idea of whether treatment cessation could eventually be a possibility down the line. At our center, which is the Imperial College London, led by my mentor, Justin Mason, who unfortunately passed away this year, it has long been recognized that there are certain patients who can enter into long-term disease quiescence and in who it is actually safe to withdraw treatment. Using the database and the cohort which we have built over the years, we wanted to formally analyze the frequency, look at the safety and analyze the factors associated with successful treatment cessation.

Can you describe the findings of your study?

In our cohort, we found that 29 of 107 (27%) patients who were still linked to care managed to successfully withdrawal treatment. The median duration off treatment was 3.6 years and the majority of these patients stopped treatment due to long term disease quiescence. To evaluate the safety of stopping treatment, we reviewed serial angiography, disease activity scores and blood biomarker data and found that treatment cessation was very safe in this cohort. We have not had any of these patients require treatment restart due to a relapse in their disease and in the longest case, one patient has been safely off treatment for more than 30 years.

Next, to gain a better understanding of the factors involved in treatment cessation, we did some exploratory analysis. We found that initial treatment response, treatment duration, and age at follow-up were predictors of treatment cessation. These results are important because they give us hope that the disease course in Takayasu may be predictable, at least in some cases, and that we may be able to move towards a process where we can stratify our patients more effectively.

In your opinion, what is the clinical significance of these results for both patients and clinicians?

In terms of the clinical significance for the patient, like I said at the start, it's important to sometimes give the patient a potential target of what might be lying ahead during their treatment pathway. These medications, especially glucocorticoids, can have significant adverse health effects when used for prolonged periods. Even the adjunctive agents, such as methotrexate and azathioprine, are associated with toxicities that require regular monitoring for safety and they pose significant issues in terms of family planning decisions which altogether can significantly impact quality of life. So, with results like ours it may be possible to eventually implement guidelines, which can reduce treatment burdens overall with more aggressive treatment tapering and cessation targets for certain patients.

For clinicians, our work highlights the importance of learning how to stratify patients with Takayasu more effectively and outlines some of the factors that should be considered when deciding whether it is safe to stop treatment. If this can be achieved, we may manage to reduce the incidence of some of the adverse effects associated with treatment. Of course, I should emphasize that patients who stop treatment should be carefully monitored for disease relapse with regular follow-up and this is something we’ve been doing at Imperial.

What about moving forward? What are the next steps for your team? Do you have any plans?

Yes, absolutely! We'd be very interested in looking at collaborating with other treatment centers to see if these results are more generalizable. This will help us address the potential confounding issues associated with conducting this study at a single investigative site. We would also like to canvass the opinions and attitudes of patients and clinicians alike towards treatment withdrawal. We recognize that certain patients might have significant apprehension when it comes to withdrawing their treatment due to the potential risk of relapse.

As a scientist, I also see that the implementation of a patient stratification framework to identify refractory vs easier-to-treat cases will provide an exciting opportunity to study the basic biology and immunology associated with refractory disease – which might one day lead to better treatments. This is something I’m thinking a lot about going forward.

Is there anything else you’d like our audience to know?

I think we’ve covered most things, but I would like to add one important note that within this population: the arterial damage done by the disease can have significant long-term effects that is not quite reversible with current approaches. A significant proportion of these patients who managed to stop treatment did have ongoing medical problems secondary to their Takayasu Arteritis. In particular, cardiovascular problems requiring attention from cardiologists were frequent. So, even though treatment cessation is a successful outcome for the rheumatologist, there is still significant disease burden within this population.

Before we wrap up, I would like to take a moment to thank my colleagues who contributed to this work, our funders at the National Institute for Health and Care Research (NIHR) UK, and, of course, the patients who are very generous with their time and their data which makes all of this possible.

Although the ACR and EULAR have introduced guidelines for initial treatment of Takayasu Arteritis, Robert Maughan, PhD, explains that there is little to no data available to guide decisions. 

Robert Maughan, PhD: Evaluating Treatment Cessation in Patients with Takayasu Arteritis 

Ingrid Torjesen is a UK-based freelance health journalist with more than 30 years of experience in health and medical communications. She works for numerous publications including Rheumatology Network, the BMJ and the Economist’s Intelligence Unit. Before her freelance career, her staff jobs included news editor of both Pulse and GP (the two leading UK weekly titles for primary care doctors), and opinion and features editor of the Health Service Journal (the UK’s leading health policy title). She also spent a few years working in Australia, including on Australian Doctor.

Thanksgiving marks the start of darker days and colder temperatures and acts as a reminder to get those annual booster shots for influenza and COVID-19. Test your knowledge on booster shots for patients with rheumatoid arthritis. 

Rheumatoid Arthritis Quiz: Annual Booster Shots

Patients with active psoriatic arthritis (PsA) who had an early response to guselkumab reported more meaningful, long-term improvement in health-related quality of life (HR-QoL) at week 100 when compared with those who did not achieve early response or were receiving placebo, according to data presented at the 

. The drug is the first fully human selective interleukin-23 (IL-23) inhibitor approved in the United States for PsA and moderate to severe plaque psoriasis (PsO). Improvements in fatigue were seen as early as week 8 and approximately one third of patients were able to maintain normative levels through week 100.

“Patients with active psoriatic arthritis may struggle with engaging in everyday tasks as a result of health-related quality of life symptoms often associated with the disease,” Philip Mease, MD, rheumatologist and Director of Rheumatology Research at the Swedish Medical Center/Providence-St Joseph Health, explained. “In these analyses, we see that achieving early clinical strides in distinct symptom domains may demonstrate future gains in health-related quality of life and fatigue improvement, which underscores the important role this therapy plays in the management of the multiple and complex symptoms of active psoriatic arthritis.”

DISCOVER-2 is a phase 3, randomized, double-blind, multicenter study assessing the safety and efficacy of subcutaneous guselkumab treatment in biologic-naïve patients with active PsA. The study analyzed 739 participants treated with the drug for approximately 2 years. This included a screening phase, a blinded treatment phase that incorporated a placebo-controlled group from baseline to week 24, and a blinded active treatment period from week 24 to week 100. The safety follow-up period continued through week 112.

Post-hoc analysis of the phase 3 DISCOVER-2 study reported that early clinical improvements of patients with active PsA receiving guselkumab were linked to meaningful improvements in overall and physical HR-QoL from week 52 through week 100, including joint and skin disease, dactylitis, and enthesitis, when compared with placebo. Patients who were not early responders also displayed benefits in long-term HRQoL when compared with the placebo cohort.

Early improvement was defined as ≥ 20% improvement in swollen joint count (SJC), tender joint count (TJC), Health Assessment Questionnaire-Disability Index (HAQ-DI), patient pain visual analogue scale (VAS), and patient Skin VAS. Other indicators were reductions in the Leeds enthesitis index (LEI) or dactylitis severity score (DSS) and clinically important improvement in the clinical Disease Activity in PsA (cDAPSA) composite score.

Another post-hoc analysis revealed that clinically meaningful improvement in fatigue was seen as early as week 8, increased between week 24 and week 52, and continued to improve through 2 years in the guselkumab-treated groups when compared with placebo. Fatigue was measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). Patients with FACIT-F improvement of ≥2 points by the 8-week mark were more likely to improve ≥4 points at week 100.

“The burden of active psoriatic arthritis on a patient’s quality of life makes the task of effectively managing the debilitating symptoms of this disease all the more urgent and challenging,” Terence Rooney, MD, Vice President, Rheumatology and Maternal-Fetal Immunology Disease Area Leader at Janssen Research & Development, LLC, concluded. “These analyses from DISCOVER-2 provide patients and physicians with critical insights as they consider the most appropriate treatment option to manage physical symptoms and help improve overall wellbeing.”

DISCOVER-2 is a phase 3, randomized, double-blind, multicenter study assessing the safety and efficacy of subcutaneous guselkumab treatment in biologic-naïve patients with active PsA. 

Early Response to Guselkumab Linked to Long-Term Improvement in Health-Related QoL in PsA

Izokibep, a unique interleukin-17 (IL-17) inhibitor, demonstrated notable dose-dependent improvements in sleep, pain, and function in patients with active psoriatic arthritis (PsA), according to data presented at the 

. The study “Izokibep, a Novel IL-17A Inhibitor, Improves Patient-reported Outcomes – 16-Week Results from a Placebo-controlled Phase 2 Study in Patients with Active Psoriatic Arthritis” revealed clinically meaningful improvements across patient-reported outcomes in those receiving izokibep, including the 36-Item Short Form Health Survey (SF-36) and Psoriatic Arthritis Impact of Disease (PsAID) subdomains.

“Psoriatic arthritis is a disease of multiple clinical manifestations including enthesitis, joint pain, skin lesions and dactylitis. Improvement broadly across all of the aspects of disease drives reduction in overall disease activity, and, as expected, also improves overall quality of life – helping patients feel better and function better,” Shao-Lee Lin, MD, PhD, Co-founder and CEO of ACELYRIN, stated.

The prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-finding trial analyzed subcutaneous izokibep 80 mg or 40 mg once every 2 weeks (Q2W) compared with placebo through week 16. Eligible patients had ≥ 3 swollen and ≥ 3 tender joints, met the classification criteria for psoriatic arthritis (CASPAR) standards, and had an inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs), or tumor necrosis factor (TNF) inhibitors.

Other endpoints included the SF-36, PsAID-9, Dermatology Life Quality Index (DLQI), Health Assessment Questionnaire-Disability Index (HAQ-DI), Treatment Satisfaction Questionnaire for Medication (TSQM-9), as well as pain, itch, and patient-reported global disease activity. Post-hoc analyses determined minimal clinically important differences (MCIDs) regarding DLQI, HAQ-DI, and PsAID-9.

A total of 135 patients were enrolled in the study between June 2020 and July 2021, with a mean age of 48.5 years, a mean PsA disease duration of 7.1 years, and a mean psoriasis (PsO) duration of 18 years. At baseline, patients had a mean HAQ-DI of 1.3, PsAID of 5.9, a numerical rating scale (NRS) itch of 4.5, swollen joint count (SJC) of 9.9, and a tender joint count (TJC) of 16.7. The visual analogue scale (VAS) global disease activity was 60.2 and the VAS pain was 62.8.

Patient-reported outcomes (PROs) reported clinically meaningful and significant improvements in PsAID, TSQM, global disease activity, and pain. SF-36 subdomains improved in those receiving 80 mg, except for Role-Emotional and Social Functioning. The most notable effects were on Bodily Pain, Vitality, Physical Functioning, and Role-Physical (p < 0.001). All PsAID subdomains improved in the 80 mg cohort, with an emphasis on sleep, pain, and function.

A DLQI ≤ 5 was attained by 81% in the 40 mg group, 80% in the 80 mg group, and 63% in the placebo cohort. Regarding the HAQ-DI, 54% of patients in the 80 mg cohort were able to reach MCID (>0.35) compared with 43% in the 40 mg group and 26% receiving placebo.

“The data continue to validate our hypothesis that izokibep offers differentiated efficacy with high potency and small size

 reinforces izokibep’s potential to manage the hard-to-treat manifestations of PsA,” Lin concluded. “The consistency of the clinical outcome and health-related quality of life measures only strengthens our enthusiasm for the ongoing phase 2b/3 study in psoriatic arthritis, the planned phase 3 program in axial spondyloarthritis, and the potential for izokibep in multiple other indications for the benefit of patients globally.”

Taylor P, Behrens F, Mease P, Wetzel D, Peloso P, Brun N, Wiens B, Brandt-Juergens J, Drescher E, Dokoupilova E, Rowińska-Osuch A, Abdel- Kader Martin N, de Vlam K. Izokibep, a Novel IL-17A Inhibitor, Improves Patient-reported Outcomes – 16-Week Results from a Placebo-controlled Phase 2 Study in Patients with Active Psoriatic Arthritis [abstract]. 

“The data continue to validate our hypothesis that izokibep offers differentiated efficacy with high potency and small size and reinforces izokibep’s potential to manage the hard-to-treat manifestations of PsA." 

Izokibep Treatment Improves Pain, Function in Patients with Active PsA 

Treatment with cannabis resulted in a short-term beneficial effect on quality of life, regarding its influence on pain, sleep, psychological, and physical domains, in women with treatment-resistant fibromyalgia, according to a study published in 

“As the worldwide use of cannabis rises, investigators question its role in treating fibromyalgia as one of the most common pain syndromes nowadays,” investigators explained. “Throughout history, different cultures used cannabis to treat pain. Modern medicine found the endocannabinoid system's role in the pathophysiology of neuropathic pain. Previous studies showed that cannabis is efficacious in promoting sleep, deepening, and lengthening the sleep cycle. Other advantages of cannabis treatment include good pain relief without significant side effects.”

The prospective cohort study used the World Health Organization Quality of Life Bref questionnaire (WhoQoL-bref), a simple, validated tool that evaluates patient-reported QoL, to better understand the impact of treatment with cannabis in 30 women aged 18-70 years with treatment-resistant fibromyalgia, defined as having exhausted pharmacological fibromyalgia treatment. The WhoQoL-bref focused on 4 domains: psychological, physical health, social relationships, and environment. The questionnaire was filled prior to cannabis initiation and at the 1-month follow-up. Patients were able to choose their route of administration, such as smoking, vaporizing, or ingestion. Patients were excluded if they were younger than 18 or older than 70, had cognitive impairment, were pregnant, or were already using cannabis treatment.

The mean age of participants was 46 years and were experiencing pain and discomfort (3.77 ± 1.3), a dependence on medication (3.07 ± 1.74), poor QoL (1.47 ± 0.63), reduced activities of daily living (1.47 ± 0.82), and poor general health (1.47 ± 0.78) at baseline prior to intervention. Environmental factors, including access to health and social care, financial resources, transport, and physical environment, were high, indicating fibromyalgia-related morbidity as opposed to environmental restraints.

At the follow-up, treatment was linked to improvements in general quality of life (1.97 out of a 5-point score, p< 0.01), activities of daily living (2.13, p< 0.01), psychological domain (1.3, p< 0.01), general health (1.83, p< 0.01), physical health (1.5, p< 0.01), and reductions in pain and discomfort (p< 0.01) and pain and fatigue (1.57, p< 0.01). Improvements were also shown in the sub-domain fields within the psychological domain, including self-esteem (1.1 points, p< 0.01), recreation and leisure (0.97 points, p<0.01), memory and concentration (1.4 points, p< 0.01), positive feelings (1.07 points, p< 0.01), and sex(1.37 points, p< 0.01). Home environment (p= 0.31) and financial resources (p = 0.07) were not impacted by cannabis treatment.

The relatively small sample size, short follow-up period, and lack of a comparison group limited the study. Additionally, biases may include the pre- and post-study design and the possibility of selection bias. However, improvements in QoL following treatment were statistically significant. Future research should examine the mental effects of cannabis as well as a time- or dose-dependent waning of treatment.

“Further studies are still indicated to understand this potential and its long-term impact,” investigators concluded. “Future epidemiologic studies should examine other confounders such as body mass index (BMI), anxiety, depression, personality disorders or traits, chronic medical issues, and various regular medications.”

Hershkovich O, Hayun Y, Oscar N, Shtein A, Lotan R. The role of cannabis in treatment-resistant fibromyalgia women [published online ahead of print, 2022 Nov 4]. 

. 2022;10.1111/papr.13179. doi:10.1111/papr.13179

As cannabis use continues to rise worldwide, investigators question its role in treating fibromyalgia, a common pain syndrome that affects women twice as much as men. 

Cannabis Significantly Improves Quality of Life in Women with Treatment-Resistant Fibromyalgia 

“ACR Convergence 2022 will have a great deal to offer practicing rheumatologists, scientists, educators, rheumatology professionals, and trainees,” said Annual Meeting Planning Committee Chair Sharon L. Kolasinski, MD, FACR, a professor of clinical medicine at the University of Pennsylvania, in a statement from the ACR.

Rheumatology Patients Report High Levels of Satisfaction With Adalimumab Biosimilar

ABP 501 is an adalimumab biosimilar that was recently approved the European Medicines Agency.

Xenofon Baraliakos, MD: Efficacy and Safety of Bimekizumab in Non-Radiographic Axial Spondyloarthritis

ASAS40 responses increased between week 16 and week 52 in patients with non-radiographic axial spondyloarthritis and ankylosing spondylitis.

Examining Drivers of Cardiovascular Risk with Tofacitinib, with Deepak Bhatt, MD, MPH

Deepak Bhatt, MD, MPH, discusses a posthoc analysis of the ORAL Surveillance trial examining drivers of increased cardiovascular risk observed in the phase 3b/4 trial in patients with rheumatoid arthritis.

Allopurinol Use Linked to Lower Risk of First-Ever Coronary Event

Exposure to more than 100 mg was linked to significantly lower odds ratios for first-ever ACS event for women.

Take 5 minutes to catch up on Rheumatology Network's highlights from the American College of Rheumatology Convergence 2022.

Rheumatology Network: ACR Convergence 2022 Highlights

The Delphi exercise, which focused on non-pharmacological treatments for pain, fatigue, depression, and sleep problems in patients with fibromyalgia, provided evidence-based expert consensus recommendations that can be used to individualize treatments in clinical practice. Results identified aerobic exercise, cognitive behavioral therapy, sleep hygiene, and education as core interventions, according to a study published in 

“[Fibromyalgia] impacts on the patients’ health and quality of life (QoL), and on their significant others and presents a significant presents a large health economic burden,” investigators explained. “Non-pharmacological interventions are often recommended as first-line treatment for fibromyalgia. However, there are currently no recommendations on which non-pharmacological intervention(s) to offer for the initial management of the different symptoms associated with fibromyalgia, and, which of these to prioritize as core treatments.”

Authors of the Canadian Fibromyalgia Guidelines Group and the European Alliance of Associations for Rheumatology (EULAR) guidelines, as well as members of the American Pain Society and clinicians with fibromyalgia expertise were invited to participate in the 3-stage, international, multidisciplinary Delphi exercise. Participants chose non-pharmacological interventions that may be helpful in treating fibromyalgia symptoms, specifically sleep issues, depression, fatigue, and pain. They were then asked to further classify treatments as either core or adjunctive. To make the decision process easier, investigators provided an evidence summary. Items that obtained over 70% of votes were accepted, while those receiving less than 30% were rejected. Items between 30-70% of votes were recirculated until a consensus could be made. After consensus was achieved, 2 patients with fibromyalgia were able to review the results and analyze them from the patient perspective.

In total, 17 experts (Europe: n = 10; North America: n = 6; Israel: n = 1) participated in the exercise and completed all 3 rounds. Ultimately, the core treatments for all symptoms were education, sleep hygiene, aerobic exercise, and cognitive behavioral therapy. Regarding pain, fatigue, and sleep problems, mind-body exercises were recommended. Mindfulness was voted as a core treatment for depression and recommended as adjunctive treatment for other symptoms. Other adjunctive treatments included music, local heat, hot bath, and relaxation. The patient representatives agreed with the results of the expert consensus and added that the patient’s preferences and past experience should play a role in prescribing these treatments.

The study was strengthened by inviting a multidisciplinary, international group of clinicians and academics to participate, including some who have worked on developing fibromyalgia guidelines. Additionally, a comprehensive list of non-pharmacological interventions was presented, along with the option to suggest other interventions for each symptoms. However, the panel members were mostly physicians, which may have led to potential bias. Another limitation was that some interventions were grouped together, such as music intervention being defined as listening to any type of music for either pleasure or therapeutic purposes. Lastly, although depression was assessed, anxiety, a common symptom, was excluded from analysis.

“Personalizing treatment for fibromyalgia using a targeted symptom approach has been suggested as a way to improve outcomes for patients,” investigators concluded. “Clinicians may find this useful as an aid to shared decision-making and treatment choices with patients as part of an individualized management plan.”

Kundakci B, Hall M, Atzeni F, et al. International, multidisciplinary Delphi consensus recommendations on non-pharmacological interventions for fibromyalgia [published online ahead of print, 2022 Sep 24]. 

. 2022;57:152101. doi:10.1016/j.semarthrit.2022.152101

Personalizing non-pharmacological treatment for patients with fibromyalgia using a targeted symptom approach may improve outcomes. 

Symptom-Targeting Non-Pharmacological Approaches Individualize Fibromyalgia Treatment 

W. Benjamin Nowell, PhD, explains the clinical significance of cross-sectional survey evaluating an online wellness program designed for patients with psoriatic arthritis (PsA), as well as the next steps for his team. Nowell is Director of Patient-Centered Research at the Global Healthy Living Foundation and affiliated with 

. Data from the study, “Managing Psoriatic Arthritis: Patients’ Views and Attitudes to Using an Online Wellness Program,” were exhibited at the 

“What’s most important is that patients need to be made aware of the options,” Nowell underscored. “They have to learn about wellness to participate in wellness programs, especially programs that are really geared toward for them towards patients living with an autoimmune disease like psoriatic arthritis.”

The program highlighted some of the challenges that this patient population faces in both living with PsA and managing their disease. Nowell, who works in patient advocacy, believes it is important that clinicians let their patients know about available programs and to reiterate the importance of sleep, stress management, exercise, and nutrition. He emphasized that simple changes, such as targeted walking goals and meditative breathing, are low energy and low cost, yet extremely effective.

“It’s important to let people know that those kinds of wellness behaviors and lifestyle changes can be really impactful on their overall health and how good they feel living with the disease,” Nowell continued.

While healthier lifestyle choices are not a substitute for medications, these changes can work with an existing program to enhance treatment and help a patient feel better.

Investigators are still recruiting for the survey, which serves as an entry point for patients living with PsA to participate in an online wellness program with a trained e-coach via the Cleveland Clinic “Immune Strength” program. The survey revealed that most patients preferred an online health coach to guide them through wellness changes, in which they can periodically check in with their coach to stay accountable.

Nowell emphasized that simple changes, such as targeted walking goals and meditative breathing, are low energy and low cost, yet extremely effective.

Implementing Healthy Lifestyle Modifications in Patients with PsA

 presentation “Managing Psoriatic Arthritis: Patients’ Views and Attitudes to Using an Online Wellness Program.” Nowell is Director of Patient-Centered Research at the Global Healthy Living Foundation and affiliated with 

“Psoriatic arthritis (PsA) is a pretty debilitating and difficult disease,” Nowell emphasized. “And although there's very effective treatments for this condition, something that we know about people living with a chronic disease autoimmune condition is that it takes more than just a medication to feel good.”

The online cross-sectional survey focused on factors, such as sleep, hygiene, exercise, stress management, and nutrition, to understand more about patients’ preferences and attitudes regarding wellness programs, as well as perceived barriers they face when adopting healthy changes. Eligible patients were adults living with PsA, currently receiving treatment, and were enrolled in the ArthritisPower registry.

“We learned some really interesting things about how they perceive wellness and wellness programs,” Nowell explained. “One of the things that stood out for me was that they perceived that cost and not having enough energy were barriers to participation.”

Moreover, approximately one third of patients were unsure of what to do or where to go to learn about healthy lifestyle changes.

“To me, that really speaks to the need that we have to help direct patients to wellness types of programs and let them know what's available and where they can participate,” Nowell concluded. “There's a real interest and need for wellness programs out there among people living with psoriatic arthritis. This is something that matters to them even more now living with a chronic disease.”

“There's a real interest and need for wellness programs out there among people living with psoriatic arthritis. This is something that matters to them even more now living with a chronic disease.”

Evaluating an Online Wellness Program for Patients with Psoriatic Arthritis 

Philip Mease, MD, takes an in-depth look into the Part B, long-term, 52-week, Phase 2 trial evaluating deucravacitinib, a novel, oral, selective, allosteric inhibitor of tyrosine kinase 2 (TYK2), as a potential treatment for psoriatic arthritis (PsA). Results of the trial, “Safety and Efficacy of Deucravacitinib, an Oral, Selective Tyrosine Kinase 2 Inhibitor, in Patients with Psoriatic Arthritis: 52-Week Results from a Randomized Phase 2 Trial,” were presented at 

. Mease is a rheumatologist and Director of Rheumatology Research at the Swedish Medical Center/Providence-St Joseph Health.

“In terms of background for deucravacitinib, a part of the reason why it's going to be a bigger deal at this meeting than it may have previously been is because it was recently approved by the US Food and Drug Administration (FDA) for the treatment of psoriasis,” Mease explained. “That's an already an unusual thing, in that the previous Janus kinases (JAKs) that had been approved in PsA, rheumatoid arthritis, and ankylosing spondylitis, kind of work in the skin aspects of psoriasis, but they're not spectacular the way interleukin-17 (IL-17) or IL-23 are.”

As a TYK2 inhibitor, deucravacitinib plays a prominent role in the signaling pathway in inhibiting IL-23, a key cytokine in the skin manifestations of psoriasis.

“The big question was whether deucravacitinib was going to be saddled with the same safety label as tofacitinib or upadacitinib because of the results of the ORAL Surveillance and that the safety label with those JAK inhibitors indicates that there is a slightly greater risk when compared with tumor necrosis factor (TNF) inhibitors for cardiovascular risk, malignancy risk, and risk of death,” Mease stated. “What surprised people a month and a half ago, when the FDA approval for psoriasis came through, was that the psoriasis division of the FDA said they were not going to require a Black Box Warning because they believed there may be a better safety profile with this specific TYK2 inhibitor compared to the rest of the JAKs.”

In Part A of the study, deucravacitinib was shown to be significantly more efficacious when compared with placebo. At week 16 (Part B), patients who did not achieve minimal disease activity (MDA) with deucravacitinib were switched to ustekinumab. The Psoriatic Arthritis Disease Activity Score (PASDAS) measured efficacy across a variety of clinical domains and any adverse events (AEs) were reported.

Decreases in mean PASDAS scores seen in Part A were maintained through week 52 in the deucravacitinib group. Additionally, clinical and patient-reported outcome improvements, including the Psoriasis Area and Severity Index (PASI), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Disease Activity Index for Psoriatic Arthritis (DAPSA), and Patient Global Assessment of Disease Activity (PGA), were also sustained at the end of Part B.

The safety profile of deucravacitinib was comparable in both Part A and Part B. No opportunistic infections, malignancy, thrombotic events, herpes zoster, or treatment-related serious AEs were reported in the deucravacitinib cohort.

“Long story short, deucravacitinib showed sustained effectiveness in all the various outcomes in psoriatic arthritis and a profile a safety profile that appears to be relatively unique and consistent, which led to its approval in psoriasis already with a good safety label,” Mease concluded. “The key next step is finishing the phase 3 trial. We're proceeding with that quite nicely in multiple countries around the world in a much bigger trial in the phase 2 trial. There are also other indications, such as lupus, among others that are being thought about for this particular drug.”

Deucravacitinib showed sustained efficacy in the various outcomes in psoriatic arthritis and a unique and consistent safety profile.
