ICYMI: 2021 Rheumatology Year in Review Save

Jack Cush, MD

Jul 08, 2022 10:00 am

Editor's note: This podcast originally appeared January 8, 2022.

“One faces the future with one’s past” – Pearl S. Buck

2021 was the year we waited for the other shoe to drop; with the pandemic stone in your shoe, you waited for:

COVID-19 to abate. While we fretted over vaccination numbers, boosters, regathering, the odd mix of politics and vacci-nots and wondering if a normal past life was possible (for our kids, jobs, churches, etc.)
Patient care to return to past normal, so we could focus on patient care
Safety: a safe way/place to resume fun, personal goals, professional development, and more

The top news stories of 2021 (general or medical) were centered around the despicables: too many rules, shortages, assured foghorns in an uncertain world, and most of all, virtual meetings. You want to evoke apoplexy or road rage? Just drop a “zoom” or “virtual” into any conversation.

Regardless of how 2021 changed our lifestyle, wardrobe, internet shopping or frequent flyer miles, rheumatology marched on in 2021. The past year resulted in major advances, game-changing drug approvals, delays, and hurdles to care and practice. While either leaned into or fought against the new normal, rheumatologists embraced their groundhog days while slowly moving the needle forward.

Herein you will find our top 10 list of advances, game-changers, worries and those better medical practices that evolved during 2021.

FDA Approvals: The FDA again said a new record for new molecular entities (drug) approvals, 50 in all (excluding vaccines, gene therapies). This included drugs for lupus (voclosporin, anifrolumab) and the novel C5a inhibitor, avacopan, for patients with ANCA-associated vasculitis. Also, new was a new biologic for myasthenia gravis, efgartigimod (Vyvgart), an antibody fragment that binds to the neonatal Fc receptor (FcRn), preventing FcRn from recycling immunoglobulin G (IgG) back into the blood.
New FDA Indications: Aside from new drugs, some previously approved drugs expanded their therapeutic indications. This included belimumab (for lupus nephritis), tocilizumab (for the ILD of systemic sclerosis, rilonacept (IL-1 inhibitor; for recurrent pericarditis), intravenous immunoglobulin (IVIG: for inflammatory myositis), secukinumab (pediatric psoriatic arthritis and enthesitis-related arthritis), upadacitinib (psoriatic arthritis, atopic dermatitis), tofacitinib (ankylosing spondylitis), baricitinib (COVID-19), apremilast (mild-moderate psoriasis)
Biologics Advancing Lupus: Game changing new drugs (or new lupus nephritis [LN] indication) were added to the arsenal – anifrolumab, voclosporin for LN, and belimumab for lupus nephritis. All for use in those on steroids and immunosuppressives, these agents will significantly advance the study and management of lupus going forward.
Super “H”: H means Hydroxychloroquine to rheumatologists. This was a hot-button drug in 2021; controversial, in short supply, but continually effective in RA and SLE. While it should be/must be vitamin “H” for SLE, in RA it also has a growing list of similar and profound effects. HCQ in both RA and SLE is associated with less cardiovascular death, lower lipid levels, lower risk of developing DM, better disease control, and in SLE, better pregnancy outcomes and overall survival. Regardless if used as Mono-HCQ, or Combo HCQ, kudos to this staple in antirheumatic therapy. You can also read Dr. Marty Bergman’s great blog called “The Nine Lives of Hydroxychloroquine”. https://rheumnow.com/content/nine-lives-hydroxychloroquine-updated
Zoomatology – technology had befallen all of us. Have you embraced it or not? What does that say about you going forward into 2022? Are you tilting against windmills or leaning into the challenge of online learning, business and engagements? Its time to invest in a new and better you; and yes, that will involve technology.
Avacopan for AAV. As mentioned above, this novel C5a receptor antagonist was approved for severe ANCA-associated vasculitis (GPA, MPA) to be used with corticosteroids. This came despite a split vote by the FDA advisory committee on its efficacy, safety and approval.
Tocilizumab – A Swiss army knife biologic this approved by FDA for Systemic Sclerosis with ILD. Previously approved for RA, polyarticular JIA, systemic onset JIA, GCA and now scleroderma. Also, this year TCZ was in high demand for its emergency use authorization for use in patients with hospitalized children or adults with severe COVID-19 requiring steroids and supplemental oxygen. The results of the faSScinate and focuSSed trials testing IL-6 inhibition (with tocilizumab; TCZ) in SSc showed preservation of lung function (meaning less further deterioration) with TCZ use, but no change in scleroderma skin progression or other measures of SSc activity. In 2021, TCZ was approved for use SSc-associated interstitial lung disease (SSc-ILD), specifically to slow the rate of decline in pulmonary function in adults SSc-ILD. The impact of this biologic approval has yet to be realized, but this approval, along with the approval of nintedinib are major advances in the treatment of SSc, one of the most challenging of all rheumatic and autoimmune disorders. https://rheumnow.com/news/icymi-actemra-fda-approved-systemic-sclerosis…
FDA Adds Warning Labels to JAK Inhibitors. The Pfizer sponsored 1133 study, the Oral Surveillance trial, assessed the safety of usual and high dose tofacitinib (compared to TNF inhibitors) in high-risk RA patients over age 50 years. In summary this trial resulted in FDA warnings about the safety of tofacitinib, especially the 10 mg bid dose, as compared to TNF inhibitors, tofacitinib had more cardiovascular deaths, more cancer events (lung cancer and lymphoma), and because of these risks, the FDA has imposed a boxed warning on tofacitinib, baricitinib and upadacitinib and also recommended these JAK inhibitors should be only tried after failing a TNF inhibitor. While these risks and regulatory changes suggest serious risks, careful review of the data shows that for many of these serious adverse events, the JAK-related number needed to harm ranges from 250 to over 700, suggesting these are infrequent events in high-risk patients are very infrequent in usual use patients.
Biologic Options for GCA: High dose corticosteroids over time carries a significant morbidity risk. Hence, the need to steroid spare, possibly with new biologics. In the past we saw no effect with ustekinumab, modest benefits with abatacept, but then came the GiAcTa study and FDA approval of tocilizumab in GCA. This past year, several novel biologics have shown efficacy in giant cell arteritis (GCA), secukinumab and mavrilimumab. The TitAIN trial presented at ACR 2021 showed that secukinumab in GCA results in 59% in sustained remission for 52 weeks (compared to 9% with steroids alone). Mavrilimumab (an anti-GM-CSF receptor-α mAb) was tested in GCA and shown to have more sustained remission at week 26 (83% vs 50%) and fewer GCA flares with steroid tapering (19% vs 46%) compared to placebo. The big questions are: 1) do we really need expensive new biologics to manage GCA? (If so, then why have rheumatologists been so, so slow to adopt the use of FDA approved tocilizumab?); 2) Will these newer biologics be proven to be cost effective and truly allow for less steroid dependence in GCA?
More IL-23 inhibitors: just when you thought there were enough biologics to treat psoriatic disease, there comes a trio of IL-23 targeted monoclonal antibodies (anti-IL-23p19), tildrakizumab (Ilumya), risankizumab (Skyrizi) and guselkumab (Tremfya) – all approved and highly effective in plaque psoriasis. Of these, only guselkumab is also approved to treat active psoriatic arthritis, but tildrakizumab and Risankizumab have shown efficacy in PsA. These IL-23 inhibitors join ustekinumab (IL-12/23 inhibitor) as new effective choices for psoriasis and psoriatic arthritis. But unlike the IL-17 inhibitors, IL-23 inhibition does not appear to be effective in ankylosing spondylitis. https://academic.oup.com/rheumatology/article/60/Supplement_4/iv1/64019…