At the end of March, I attended the RheumNow Live 2022 conference. This event offered clinical context, comprehensive lectures from rheumatology experts, and audience input that would be greatly beneficial for all of our members. I encourage you all to read my overview and takeaways to improve your practice.

Here I will give you all a condensed recap of each session of this premiere experience:

Adherence to RA Therapies

Kaleb Michaud, Ph.D. began his lecture with an update on patient satisfaction numbers from 2006 to 2021. Through these years 84% of patients were satisfied with their medications—up from 77%. Those satisfied with control dropped to 37% from 53%, those unwilling to change dropped to 50% from 64%, and those very satisfied with meds yet high disease activity increased to 35% from its prior 25%.

Dr. Michaud discussed that efficacy, safety, adherence, and costs equal the effectiveness of the medication, and there is approximately 50% adherence to long-term medications. It was found that patients who take their medications in the morning are more adherent than those that take them in the evening.

Patients’ failure of self-management (ex. lifestyle, exercise, and self-efficacy) contributes to comorbidities such as heart, lung, CNS, age, and depression, which further contributes to poor outcomes.

Dr. Michaud concluded with a discussion on mood questions to ask at each patient visit as well as deliberate ones such as, “When is your MTX day?” “When is your injection day?” If questions are answered quickly without a lot of thought will help determine if patients are compliant with these therapies.

Drug Targeting in PsA

Bruce Kirkman, MD reminded us that Psoriatic Arthritis (PsA) is not Rheumatoid Arthritis with a rash. PsA has a unique set of symptoms and co-morbidities and has no known exact cause. Rather genetic, environmental, and immunologic factors play key roles. Dr. Kirkman discussed that genetic variants within genes involved in four broad immunological processes; skin barrier function, T-cell signaling, NFkB pathway, and antigen presentation are found to be associated with PsO and PsA.

He also talked about the key inflammatory cytokines in spondyloarthritis, IL17/23, and TNFα, explaining the history and the timeline of IL-17A and IL-17 producing T-cells. He discussed how cytokines drive the differentiation of Naïve T helper cells and presented flow cytometry to support that IL-17 producing CD8 cells is elevated in synovial fluid of PsA patients and not RA patients.

Dr. Kirkman presented information on the role of IL-17A in enthesitis which causes cartilage degradation and inflammation. Cellular sources of IL-17 are found in both the innate cells and adaptive cells. JAK pathways in cytokine production and signaling are found within the inflamed PsA joints.

The lecture concluded by focusing on remission in practice. Remission rates are around 20-60% in trials with bDMARDs, factors that are associated with remission are younger age, low functional impairment, and a high C-reactive protein. In randomized clinical trials, the achievement of minimal disease activity is associated with less damage progression and improved quality of life and function. However, the nature of clinical features and co-morbidities are important guidelines for choosing the best therapy for each patient.

The Blind Men and the Kidney

The first words in Joan Merrill, MD’s lecture were “One drug does not fit all.”

Dr. Merrill discussed the lack of new guidelines which have not seemed to change in 10 years. MMF or Cyc have about the same results. In studies for LN, there is no placebo group due to the severity of their disease. Patients with LN who do not improve in the 1st six months face an increase in their problems.

She presented a slideshow where the pathology correlates in the kidney. Class I is minimal mesangial. Class II is mesangial proliferative. Class III is focal endocapillary +/- extracapillary proliferation with subendothelial deposits and moves into the glomerulus. This class can be active, chronic, or both. Class IV is diffuse endocapillary +/- extracapillary proliferation with subendothelial deposits. This class can be active, chronic, both, segmental or global. Class V is thickened basement membrane with subepithelial deposits. There is also tubule interstitial disease which occurs in the tubule. Class III and IV will have immune debris and inflammatory substances which is a bad diagnostic sign.

Dr. Merrill examined the anecdotal evidence that LN may respond to immune suppression. The goal of therapy is to decrease activity. She explained that the life expectancy of patients on dialysis is 10 years. There is evidence that patients that were placed on type 1 IFN did very well. When a question about the use of Vitamin D for LN was asked, she explained that it should be used only if the patient is deficient in vitamin D.

The Novel Treatment of SLE

Beginning with the history of the drug development in SLE, Sonali Narain, MBBS, MPH discussed how no new medications were approved to treat SLE from 1955 to 2011. We only had ASA, corticosteroids, or HCQ until Belimumab was approved for use in 2011.

Dr. Narain presented a slideshow of the proposed MOA of HCQ. Multiple studies indicated that the rate of flares increases when HCQ is decreased or discontinued. She highlighted the risk of retinopathy which doubles for every additional 5 years of use and is increased with higher dosing. She also explained that we need to continue to promote adherence to HCQ.

In covering 2021 updates it was found data from 5 belimumab studies showed a 39% reduction in the risk of severe flares when using BEL, more patients had a GC reduction, and fewer patients have a GC increase. Crude mortality rates were similar across years 1-3, and crude malignancy rates for year 3 were numerically higher than year 2 but similar to year 1. In one study, regarding sequential therapy, with BEL and RTX, the primary endpoint of reduction in dsDNA level was achieved at wk52 and the decreased risk of the severe flare was achieved vs. placebo. Yet one study did not achieve the primary efficacy endpoint-proportion of patients with disease control at wk52 without the use of other immunosuppressants and prednisone and more serious infections were seen in the BEL+RTX group.

Her presentation also addressed a small study of BEL in pregnancy of 13 patients with an average age of 38 who had 2 treatment courses with BEL and were on concurrent medications primarily ASA, HCQ, GC (all 13), AZA-11, LMWH (low molecular weight heparin)-6, IVIg-4 and SSZ-1. The pregnancy outcomes were 3 terms, 8 preterms, and 2 miscarriages. During the neonatal period, 6 were in respiratory distress and 6 were uneventful, and 1 other. 3 were PPROM (preterm premature rupture of membranes), and 2-Antepartum hemorrhage. This study found we need more data to assess the safety of BEL in pregnancy.

Dr. Narain then presented the history of interferons in SLE. In 2021 the FDA approved the first Type 1 INF targeting therapy in SLE. She presented data from two studies of the anifrolumab phase III studies. Anifrolumab improves rash and arthritis symptoms in patients however patients need to be vaccinated for shingles before use.

Finally, Dr. Narain discussed several new therapies on the horizon waiting for the phase 3 results to be presented. Telitacicept, IL2 restoration, Iberdomide, Litifilimab (BIIB059), Chimeric Antigen Receptor-T cells, Proteasome inhibitors, Dapirolizumab, Baricitinib and Bruton tyrosine kinase inhibitors.

Precision Medicine in RA

Ernest Choy, MBBCh, MD, MRCP, FRCP began with a history of precision medicine and rheumatology. Ideally, biomarkers would help clinicians select an optimal therapeutic strategy for patients.

Dr. Choy discussed an absence of association between anti-CCP (+) and response to anti-TNFs. He reviewed that different synovial pathotypes and molecular signatures exist at the time of diagnosis and are associated with disease activity, radiographic progression, and response to DMARDs. He went on to discuss the molecular portraits of early rheumatoid, identifying the clinical and treatment response phenotypes and showed the evidence for 3 distinct phenotypes: Lympho-myeloid, Diffuse-myeloid, and Pauci-imm in the synovial fluid. Pathotypes are associated with molecular gene expression. The method for determining the phenotype is done with a synovial biopsy (which most patients are reluctant to do.) He mentioned that the Pauci-imm phenotype is the least likely to respond to MTX.

Dr. Choy showed a slide that supported baseline synovium plasma cell gene expression is associated with CCP antibody positivity and worse prognosis at 12 months and that RA synovial molecular signatures are associated with radiographic progression. He added that sero+ patients will respond well to RTX and ABA.

He also spoke on the gut microbiome and the role that would play to predict response to DMARDs. Dr. Choy discussed that we could change the microbiome with NSAIDs, and stated that in theory NSAIDs are bad for the gut, yet no real data or studies are available to confirm this. While there is also no literature to support the use of probiotics, they are not harmful.

Dr. Choy explained how precision trials for RA would be designed and that precision medicine delivering tailored treatment for the individual patient is a major global research objective. He noted that the RA pathology will change over time due to the medication we use and that once we learn the phenotype machine learning will map out the treatment for the patients.

Treatment Choices in Refractory RA

Jack Cush, MD ushered in the meeting with a discussion of refractory RA. He called them D2T-RA, difficult to treat RA, and only 10% fall into that category. 90% of RA patients can be managed successfully which is encouraging. Some reasons for those patients are multidrug-resistant (34%), difficult comorbidities (10%), or socioeconomic reasons (56%). He stated that D2T-RA is to understand the disease state, define the problem and change the approach.

He discussed the importance of learning the patient’s desired outcome within their therapy, and he proceeded to highlight the 4 wrongs.

1. The wrong diagnosis – is seronegative RA (SNRA) RA?
   He presented a 10-year study of 435 early SNRA pts. 3% became erosive or SPRA, 32% could not be reclassified and 65% evolved to other diagnoses; PMR 16%, PsA 11%, SPA 9%, and Osteoarthritis 10%. Dr. Cush added that the more atypical the presentation would lead to longer times to diagnosis, the more DMARD failures would increase, and the more biological failures and drug toxicities we would see. Other considerations with non-response are fracture, mechanical/degenerative disease, occult bizarro infections, or others-malignancy, CPPD, or PsA.
2. Wrong drug.
   The number of choices in RA continues to increase. Currently, we have 9 biologics, 13 biosimilars, 3 JAK inhibitors, and 6 DMARDs. More drugs are not the answer to D2T-RA. He asked if we could better characterize the patient with imaging/ultrasound, biopsy, genomically-precision medicine, or biomarkers. Dr. Cush added we need smarter use of the existing RX options, and gave the example of machine learning to identify a rule to predict response to sarilumab in patients with RA.
3. Wrong patient.
   Phenotype does not predict refractory RA. Dr. Cush presented his “Hell Traits”: Noncompliance, negativistic thinking, poor patient managers (be the CEO of your health), poor sleepers (depression/anxiety), chronic pain seekers, and vacci-not, magical thinkers, different drummers.
4. Wrong doctor.
   Second opinions are a good thing. They are not failures. But Dr. Cush discussed that delays in referral equal poor outcomes. Second opinions typically confirm the original diagnosis or treatment regimen, and 90% of patients with poorly defined conditions remain undiagnosed. 10%-62% of second opinions yield a major change in the diagnosis, treatment, or prognosis, and more patients receive different advice on treatment than on diagnosis.

Dr. Cush emphasized listening to the patient, “They will tell you their diagnosis.” He shared that decision-making is vital to increasing compliance and adherence, decreasing the cost of care, and increasing patient satisfaction and trust.

In closing, Dr. Cush examined common mistakes in RA prescribing including aiming for monotherapy, not maximizing MTX, AZA, SSZ, or CyA., believing LDAS/Remission is invited to weaning, relying on, or stopping corticosteroids (do flares = D2T-RA?) or waiting to change DMARDs (go, no-go decisions @6, 12, or 24 wks.)

Summary

This premiere conference was an informative event that offered crucial education to improve our methods and the quality of our patient’s health. The current studies presented and interactive discussion offered new research that I believe is essential for our organizations and members to apply to their practice. I hope you all can glean these takeaways from this year’s RheumNow Live to advance your practice and the health of patients of rheumatology.