 and osteoporosis are common conditions in which millions of patients are affected worldwide. Despite the common nature of the diseases, patients are not often regularly scanned to see if they have 1 of them. Instead, they suffer pain and have an increased risk of fragility fractures and worse quality of life.

Nancy Lane, MD, of UC Davis Health is an expert in osteoarthritis and osteoporosis who spoke at the 

 2020 meeting about the state of both diseases today. 

had the opportunity to speak with Lane about the 2 spaces, popular agents for the treatments of the diseases, and why patients are being scanned regularly for the conditions.

What’s going on in the world of osteoarthritis right now?

 It's an exciting time in the space of osteoarthritis. There's tremendous work being done in the basic science of the disease and there are some very exciting translational phase 2-type studies that are right now recruiting patients that are looking at agents that can stimulate the cartilage to grow and thicken, that can reduce the degradation and increase cartilage matrix formation. There are studies just reported where inhibitor seville 1 reduced joint replacements over 3.5 years by over 50% and a group of agents that by themselves don't reverse or slow the course of the disease, but are an actual inhibitor of pain in the joint by a novel pathway of inhibiting nerve growth factor, that compound tanezumab may be available to our patients in the early part of next year.

So, those are some examples of the excitement in terms of new therapeutics. In addition, although I will not be spending a lot of time talking about this, there finally has been a way to get stem cells to turn into cartilage and grow cartilage. It's a little bit complicated, but it requires some skeletal stem cells and then giving it a growth factor and a factor to inhibit new blood vessel formation, anti-VEGF, and cartilage has now been generated in a mouse where there's been a defect. And if we can translate any of that to the clinic, we're really going to be able to help our patients.

: What agents are you most excited about?

 Well to inhibit pain for a prolonged period of time, I'm excited about the inhibition of nerve growth factor of the tanezumab work. For the IL-1 inhibitor, the data are for canakinumab. The stem cell work is in its infancy and is being done out of Stanford.

You’re also an expert in osteoporosis. How do you individualize treatment for that condition?

 Well, that's a great question. We look at it in terms of patients who are at high risk for fracture and we try to prevent fractures by giving them long-acting bisphosphonates or other inhibitors. Then we have patients who present to us and they've already had fragility fractures. And for those patients I will emphasize starting them on an anabolic agent, either teriparatide, abaloparatide, or romosozumab followed then by a strong and resorptive agent to maintain that bone that they have gained and maintain their improved bone strength.

It's interesting you bring up bisphosphonates. I was actually just looking at an abstract that was presented earlier today at the North American Young Rheumatologists Investigator Forum and the investigators noted how osteoporosis is a condition a lot of patients are not necessarily screened for. Why is that?

Well, that's a great question. There's been a sea change over the last 10 years. Ten years ago, many physicians had bone density machines in their office, and they would do the scans right there and interpret them. However, there was a change in reimbursement and it resulted in many of the bone density machines no longer being available, except in hospitals or in large clinics, which for some reason, has reduced physicians and healthcare providers’ interest in getting bone densities, and the result being less people are treated for their osteoporosis and then osteoporosis comes to the attention of the physician later when there's a fragility fracture. That alone is a diagnosis of osteoporosis. But actually, screening and treating people at high risk, we're lucky if we can do it, lucky if it's done at age 65.

Now, the guidelines are very clear. All women should have a bone density scan at age 65 and all men at the age of 70. Women below the age of 65 should if they've had a fragility fracture or have significant risk factors. So, all women for the most part should be screened by age 65 and all men at age 70, but that's rarely happening today. As a result, we are seeing more fragility fractures in our population.

Well, the first fracture by itself, say it’s a vertebral fracture, may not be detrimental. But 1 fracture significantly increase your risk of another fracture and another fracture, at which point, with the vertebral fractures, you're losing height, you're bent over, and your quality of life goes down. So, we really need to try to recognize that first fracture and get it treated. If we can't do it before the fracture, then we definitely need to do it when they first have a fragility fracture.

: How are you able to do that without the machinery?

Well, it's difficult, but the patients who have a clinical or painful vertebral fracture, or an osteoporotic fracture fragility fracture by say, falling from a high standing height. Hopefully they will get referred to fracture liaison services or to doctors that will work them up. Otherwise, if we don't catch them at the first couple of fractures, that's a bad position to be in. So, we all have to be on the lookout for these patients. Rheumatologists are very good at identifying these patients. We see older patients with other musculoskeletal ailments and rheumatologists tend to be pretty vigilant about getting bone densities, assessing our patients, treating them, and following them.

: Is there anything else you would like to add about osteoarthritis or osteoporosis that is happening right now?

The most important thing is that physicians recognize the need for every woman over 65 and every male over 70 to have a bone density scan. If they're treated, remember after 3 years to check their bone densities to see if they've improved, or if they haven't fractured and they've been on intravenous bisphosphonates, then they should have a drug holiday. If they've been on oral for 5 years and they aren’t having fractures and their bone density is good, they should be on a drug holiday and remember to follow them. Remember to see them in about 2-3 years and reassess them because many patients after these holidays slip back into needing therapy.

Another very important thing to remember is osteoporosis is like any chronic disease of aging. Once you have it, you always have it and your risk of fracture may change but you need to assess for it the rest of a patient's life.

Articles

Congress of Clinical Rheumatology East

An expert discusses the state of screening, diagnosing, and treating osteoarthritis and osteoporosis.

Nancy Lane, MD: The State of Osteoarthritis and Osteoporosis

Among measures examined to detect changes in 

, the Psoriatic Disease Activity Score (PASDAS) is the most sensitive and has the highest ability, according to new study findings presented at the 

The findings could inform the planning of future studies that use composite measures to evaluate psoriatic arthritis therapies.

Laura Coates, MBChB, MRCP, PhD, and investigators examined the relative performance of 5 continuous composite measures— Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), Disease Activity Index in PsA (DAPSA), and PASDAS—used in a phase 3, randomized trial in patients with psoriatic arthritis that compared methotrexate monotherapy with etanercept monotherapy and with a combination of the 2.

The phase 3 trial, “The Study of Etanercept And Methotrexate in Combination or as Monotherapy in Subjects with Psoriatic Arthritis,” was a 48-week, double-blind, randomized, multicenter, international, controlled trial. Eligible patients were at least 18 years old with active psoriatic who were naïve to etanercept and other biologic agents. The patients had at least 3 tender and at least 3 swollen joints.

Patients were randomized 1:1:1 to weekly treatments of either oral methotrexate monotherapy plus subcutaneous placebo, subcutaneous etanercept monotherapy plus oral placebo, or combination therapy of subcutaneous etanercept plus oral methotrexate. Methotrexate doses were initiated at 10 mg/week and titrated up to 20 mg/week over 4 weeks. Etanercept was administered at 50 mg/week.

There were mean improvements from baseline to week 24 in DAS28-CRP, CDAI, and SDAI. Of the patients enrolled, 691 completed the trial. More patients achieved ACR, Minimal Disease Activity, and Very Low Disease Activity responses at week 24 in the etanercept-containing groups compared with methotrexate alone. There were greater mean changes in DAS28-CRP and PASDAS continuous composite measures from baseline to week 24 in the etanercept groups compared with methotrexate monotherapy. The mean changes from baseline to week 24 for CDAI, SDAI, and DAPSA were similar among all groups but slightly higher in the etanercept groups.

For all 5 continuous composite measures, the etanercept groups had numerically larger effect sizes and standardized responses than methotrexate monotherapy. PASDAS had the most pronounced difference between the etanercept groups and methotrexate monotherapy.

Changes in tender and swollen joint counts were the main drivers of changes in composite scores for DAPSA, DAS28-CRP, CDAI, and SDAI. The main driver of changes in the PASDAS score was in the Physician Global Assessment and the Patient Global Assessment.

Coates and the team noted measures that covered multiple domains, like PASDAS, might be optimal for quantifying psoriatic arthritis disease burden as they showed the greatest sensitivity to change and better represented the breadth of disease manifestations.

The Performance Characteristics of Composite Measures Used in a Randomized Trial Examining Etanercept and Methotrexate as Monotherapy or in Combination in Patients With Psoriatic Arthritis

,” was published as part of the Congress of Clinical Rheumatology 2020 meeting.

Which composite measures detect the highest level of changes in psoriatic disease activity.

PASDAS Sensitive at Detecting Changes in Psoriatic Disease Activity

worsening as a result of changing treatments due to partial or inadequate response, a new study finds. In fact, more than half of such patients treated with adalimumab who had switched to sarilumab experienced clinically meaningful improvements.

Clinical Congress of Rheumatology (CCR) East 2020 meeting.

Current guidelines recommend making any necessary therapeutic adjustments if rheumatoid arthritis patients fail to meet treatment goals or remission. Although patients may express health concerns over switching, there have been no data that assesses the association between therapy switching and disease exacerbation.

To fill this gap, a team led by Jeffrey Curtis, MD, MS, MPH, Professor of Medicine at the University of Alabama at Birmingham, performed a post-hoc analysis of the MONARCH Open-Label Extension (OLE) study and evaluated the effects of switching from adalimumab to sarilumab in patients who had partial response to treatment.

Patients who had been randomized to receive 40 mg of adalimumab during the double-blind phase were then transferred to receive 200 mg of sarilumab at the start of the extension study. Those initially receiving sarilumab continued with the regiment during open-label.

The extension study had enrolled a total 320 patients, and 155 ended up switching to the sarilumab group, with 165 maintaining sarilumab treatment.

At OLE baseline, 52% of the population had experienced partial response during the double-blind phase. The investigators noted that, as expected, partial responders were more prominent in the switch group (59%)—versus the continuation group (45%).

Furthermore, the continuation group partial responders had similar but numerically lower disease activity scores at OLE baseline—with the exception of tender joint count (TJC) and swollen joint count (SJC).

For the post-hoc analysis, Curtis and team defined partial response as patients with continued moderate-to-high disease activity (Clinical Disease Activity Index [CDAI] > 10) at OLE baseline, regardless of if minimal clinically important difference (MCID) and CDAI had improved following the double-blind phase.

The MCID threshold for patients with high-disease activity at double-blind phase baseline (CDAI<22) was 12 units. The threshold for those with moderate disease activity was 6 units.

After week 24, they noted that only a few partial responders in the switch (6%) and continuation (4%) experienced a worsening of disease activity.

On the contrary, up to 57% of patients in the switch group and 43% in the continuation group experienced improvements in disease activity.

There was no observed change of disease activity in 37% and 53% of the switch and continuation cohorts, respectively.

And finally, the team reported that between OLE baseline and week 24, the mean changes in efficacy parameters and patient reported outcomes had numerically increased. The only exception was SJC28.

“A small risk of worsening with the substantial likelihood of meaningful improvement may help alleviate patient fears of worsening when considering a switch to an alternative therapy, such as sarilumab,” they concluded.

Low Probability of Clinical Worsening Following Switching Biologic Disease-Modifying Antirheumatic Drug in Patients with Rheumatoid Arthritis and Partial Response to Adalimumab

In the MONARCH OLE study, more than 50% of patients with rheumatoid arthritis who had low or inadequate response to adalimumab and switched to sarilumab experienced an improvement in disease activity. 

Switching Antirheumatic Therapies Has Low Risk of Clinical Worsening

radiographic axial spondyloarthritis (r-axSpA

), even as early as the first follow-up visit, according to new findings presented at the 

Clinical Congress of Rheumatology (CCR) East 2020 meeting

These symptoms typically include fatigue, pain, stiffness, and sleep disturbances, which negatively impact the patient’s health-related quality of life. 

Atul Deodhar, MD, MRCP, Professor at the Oregon Health and Science University of Medicine, and colleagues, assessed the data from the COAST-V and COAST-W studies in order to evaluate the high-affinity monoclonal antibody’s impact on r-axSpA symptoms. Both studies were phase 3 randomized controlled trials that originally evaluated the safety and efficacy of the drug in both biological disease-modifying antirheumatic drug (DMARD)-naïve and tumor necrosis factor inhibitor (TNFi)-experienced patients with r-axSpA.

In the COAST-V study, a total of 341 patients were randomized to receive ixekizumab in two different dosing schedules (every 2 or 4 weeks), placebo, or adalimumab for 14 weeks. An extended treatment period with different dosing schedules for each arm was conducted between weeks 16-56.

For the COAST-W study, 316 paritcipants were enrolled and assigned to either one of two dosing schedules for ixekizumab or the placebo group. Similar to the COAST-V study, the double blind period was conducted until week 14 followed by an extended treatment period from week 16 to week 52.

Both studies included patients ≥18, who had an established diagnosis of r-axSpA, a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4, and a total back pain score ≥ 4, among other eligibility criteria.

They excluded patients with a serious infection ≤12 weeks prior to enrollment.

Assessments used at baseline and in follow up weeks until week 52 were the Fatigue Numeric Rating Scale, Patient’s Global Assessments of Disease activity, global spinal pain, spinal pain at night, and Jenkins Sleep Evaluation Questionnaire (JSEQ).

Deodhar and colleagues noted that over the course of treatment, patients experienced significant improvements in all measurements and assessments. Furthermore, these reductions were sustained through the extended treatment period.

These improvements for ixekizumab-treated patients were observed at the first post-baseline visit for each assessment. For example, Ixekizumab’s effects on fatigue were reported at week 8, disease activity at week 1, global spinal pain at week 1, and spinal pain at week 1. 

JSEQ score improvements were observed at the second post-baseline assessment, or week 16.

Overall, the investigators lauded the drug’s efficacy in reducing r-axSpA-related symptoms and improving patient quality of life.

Ixekizumab Improves Fatigue, Pain, and Sleep up to 52 Weeks in Patients with Radiographic Axial Spondyloarthritis

Patient assessments measured fatigue, disease activity, global spinal pain, and spinal pain at night.

Ixekizumab Improves r-axSpA Symptoms Affecting Quality of Life

The more healthcare workers can collaborate with each other, the better care they can give to patients. That’s because every patient has distinct features and do not fit into individual boxes.

“With my rheumatology colleagues I find communication is the biggest thing,” Ashley Crew, MD, of Keck Medicine of USC, said in a recent interview with 

Rheumatologists and dermatologists often work together to make the best treatment decision. Crew has a multidisciplinary clinic where she and a rheumatologist see a patient synchronously. They work together and there is the benefit of having the same history and assessment and the providers can talk in and out of the room to come up with a treatment decision.

Other times, however, practice does not look like that, she said. Most of the time she shares patients with providers who are either in the same facility or a completely different setting in a different part of her city.

“I think no matter what, as long as we’re communicating with each other, then we can really be beneficial to each other and again help for diagnostic purposes and also for therapeutic interventions and how we can better maximize them,” Crew concluded.

Videos

How providers of multiple specialists can come together to help 1 patient.


Ashley Crew, MD: The Relationship Between Healthcare Specialists

If something is out of a provider’s wheelhouse, they may inaccurately prescribe something to a patient. That means the provider could be unsure about the side effects to a prescription or exactly how it can benefit a patient or be used.

, Ashley Crew, MD, of Keck Medicine of USC, said that comes into play a lot in rheumatology—and other specialties—with topical steroids.

One of the biggest issues Crews, a dermatologist, sees, is a failure of the provider to pick the appropriate strength topical steroid, whether it be low, moderate, or strong potency.

“We basically decide which class we want to use depending on the location we’re treating and the disease-process we are treating,” Crew said. “So, the strength is 1 important component, and oftentimes non-dermatologists undershoot with strength because they are anxious and don’t want to treat with something too strong because they are worried they might do damage, which I think is a good caution to have if you haven’t been coached on how to do it appropriately.”

It is also necessary to think about the actual steroid being used—a solution, a cream, or an ointment. That’s important because it affects the potency of the topical steroid and if the patient hates what is prescribed to them, they aren’t likely to use it.

For example, if someone presents to the rheumatologist with scalp psoriasis and is prescribed an ointment, they likely will not use it, Crew said. Instead, if an alcohol-based solution is prescribed, it might better be suited to address the needs of the patient while actually being used and benefitted from.

Ashley Crew, MD: Barriers to Topical Steroid Use

, Randall Cron, MD, PhD, Professor of Pediatrics and Medicine, University of Alabama at Birmingham, discussed his presentation on 

Clinical Congress of Rheumatology (CCR) East meeting.

Cytokine storm syndrome is a generic term that envelops various hyperinflammatory conditions—such as macrophage activation syndrome (MAS) and hemophagocytic lymphohistiocytosis (HLH)—yet it would be inaccurate to consider them all identical. Cron stressed the importance of their distinctions, which influences identification within patient populations and treatment decisions.

He also briefly touched on genetic predispositions to these conditions, hinting at a potential novel gene that physicians and rheumatologists should be aware of.

Additionally, he talked about the intersection between cytokine storm syndrome and 

“Many of us think that COVID-19 has a cytokine storm. It falls under that umbrella as well,” he said. “It’s unique from other cytokine storms, but it has enough features that treating the cytokine storm is really important to prolonged survival.”

He went on to explain that if patients become hospitalized due to the virus, and present with inflammation or show evidence of a cytokine storm, then an intervention becomes all the more necessary.

Although proper interventions are uncertain at the moment, there is some emerging evidence that moderate doses of glucocorticoids may increase chance of survival.

“Maybe even some of the targeted approaches that we use in rheumatology to go after individual cytokines or groups of cytokines may also be beneficial,” Cron concluded.

COVID-19 is associated with its own cytokine storm syndrome.

Randall Cron, MD, PhD: Cytokine Storm Syndrome and COVID-19

-associated interstitial lung disease use non-biologic disease-modifying antirheumatic drugs (DMARDs) including azathioprine, mycophenolate mofetil, and mycophenolic acid, according to new findings presented at the 

Clinically significant interstitial lung disease occurs in nearly 10% of patients with rheumatoid arthritis. The condition leads to significant morbidity and premature mortality. The five-year mortality in usual interstitial pneumonia is greater than 50% while non-fibrotic nonspecific interstitial pneumonia with cellular or fibrotic pattern carries a more favorable prognosis.

While corticosteroids and DMARDs are used, treatment guidelines for the extra-articular manifestation of rheumatoid arthritis do not exist.

Fatima Alduraibi, MD, and investigators established a local rheumatoid arthritis-associated interstitial lung disease registry and aimed to use it to study the outcomes of patients with the condition.

Alduraibi and the team included adult patients with a diagnosis of rheumatoid arthritis and interstitial lung disease who were treated at the University of Alabama Birmingham between January 2010 and December 2019. The team reviewed charts to identify rheumatoid arthritis-associated interstitial lung disease based on ACR 1987 or 2010 ACR/EULAR criteria and an expert pulmonologist diagnosis.

The investigators collected data on demographics, antibody status, lifestyle habits, and pulmonary function measurements. Further, they gathered information on medications used to treat rheumatoid arthritis-associated interstitial lung disease.

Overall, 103 patients met the definition of rheumatoid arthritis-associated interstitial lung disease and were included in the study, and the team presented characteristics of 36 patients. The mean age of diagnosis of interstitial lung disease was 64 years old. A majority of the patients were women (57%) and 69% were Caucasian. Half of the patients were past smokers and 44% had never smoked.

The rheumatoid factor was positive in 72% of patients while the anticyclic citrullinated peptide was positive in 83% of the patients. Using high-resolution chest computed tomography scans, it was revealed 55% of patients had usual interstitial pneumonia and 17% has nonspecific interstitial pneumonia.

When the investigators looked at treatments for such patients, 39% were on azathioprine, 39% were on mycophenolate mofetil and mycophenolic acid, 11% were on rituximab, and 11% were on anti-fibrotics.

In univariable analysis the team found FVC and DLCO at 12 months were stable and there was no statistically significant change in FVC in the rituximab subgroup (

The team noted further statistical analysis was still ongoing.

Outcomes of Patients with Rheumatoid arthritis (RA) Associated Interstitial Lung Disease (ILD) Treated with Immunosuppressive Medications

,” was published as part of the Congress of Clinical Rheumatology East 2020 meeting.

A majority of patients with the condition are on azathioprine or mycophenolate mofetil and mycophenolic acid.

DMARDs for Patients With Rheumatoid Arthritis-Associated ILD

According to new research presented at the North American Young Rheumatology Investigator Forum (NYRIF 2020), patients diagnosed with 

interstitial pneumonia with autoimmune features (IPAF)

 were found to have similar demographic and imaging characteristics as those with connective tissue disease-associated interstitial lung disease (CTD-ILD).

Furthermore, these commonalities were distinct from patients with idiopathic pulmonary fibrosis (IPF).

Those who are diagnosed with IPAF have ILDs with specific clinical, serologic, and/or morphologic autoimmune characteristics that fail to meet criteria for any specific CTD. And yet, it has been uncertain whether its clinical presentations and prognoses have any similarities with CTD.

A team led by Nikhil Jiwrajka, MD, resident at the Hospital of the University of Pennsylvania, conducted a retrospective review of patients with ILD to compare characteristics, treatment patterns, and outcomes between IPAF patients and CTD-ILD and IPF patients.

Each patient was given an ILD diagnosis by a panel consisting of pulmonologists, a radiologist, and a pathologist and which was based on a comprehensive multidisciplinary evaluation.

Using medical records to aggregate further information from the patients’ initial presentation, Jiwrajka and team then recategorized patients as IPAF, CTD-ILD, or IPF.

They then proceeded to compare clinical characteristics, imaging findings, baseline pulmonary function tests, treatment patterns, and transplant-free survival rates among the groups.

According to their analysis, the investigators identified 56 patients with IPF, 122 with CTD-ILD, and 129 with IPF.

Compared with IPF patients, those with IPAF and CTD-ILD were mostly female (67.4% vs. 30.2% IPF; 

 < .05), less likely to have smoked (45.5% vs 68.2%; 

 < .05). and more likely to have seen a rheumatologist (77.5% vs 5.5%; 

The investigators also noted that baseline imagining findings were similar between IPAF and CTD-ILD groups.

Although CTD-ILD patients were more likely than IPAF patients to have received immunosuppression prior to their initial visit (70.5% vs 49.1%; 

 < .05), treatment patterns during follow-up were reported as similar between the groups.

A greater proportion of IPF patients, however, received antifibrotic agents during follow-up (35.7% vs 6.2%; 

Finally, the team found there to be no significant difference in median transplant-free survival between IPAF patients and CTD-ILD or IPF patients. There was, however, a longer median survival in CTD-ILD patients than in IPF patients.

They acknowledged that the many similarities in demographic and imaging characteristics between IPAF and CTD-ILD patients suggest a possibility of a common underlying disease process.

“Ultimately, the future identification and study of IPAF patients requires a comprehensive clinical and diagnostic evaluation by a multidisciplinary team that includes both pulmonologists and rheumatologists,” they concluded.

Phenotypic Characteristics and Treatment Patterns of Patients with CTD-ILD, Idiopathic Pulmonary Fibrosis, and Interstitial Pneumonia with Autoimmune Features," was presented at NYRIF 2020.

These findings suggest the possibility of a common underlying disease process between the two pathologies.

IPAF Shows Demographic and Imaging Similarities with CTD-ILD

Clinical manifestations may lead to a rheumatology patient needing to seek additional care from a dermatologist.

Conditions like psoriatic arthritis and psoriasis are seen all the time by dermatologists, Ashley Crew, MD, from Keck Medicine of USC, said in a recent interview with 

. Crew, who is a dermatologist, said a lot of patients go to her with suspected inflammatory arthritis and there is a question about whether it is psoriatic arthritis.

“I think it comes as a surprise to a lot of dermatologists that psoriatic arthritis is not a slam dunk always diagnosis and that there can be some grey area,” Crew said.

When rheumatologists debate about whether a patient has psoriatic arthritis, dermatologists are often asked to assist with rashes and other possible manifestations.

There are also tons of overlap with lupus. Such patients might have systemic lupus who also have cutaneous manifestations of the condition that can be acute, chronic, or sub-acute. Further, there are manifestations of dermatomyositis that dermatology clinics see a lot of that are rheumatology patients who they help to assess, make a diagnosis, and help to fine-tune therapeutics.

When a rheum patient might need to consult with a dermatologist.

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