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What's new in rheumatology

What's new in rheumatology
Philip Seo, MD, MHS
Literature review current through: Nov 2022. | This topic last updated: Dec 16, 2022.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.


Gout flare and risk of subsequent cardiovascular event (August 2022)

Gout is known to be associated with cardiovascular disease; however, the temporal association of cardiovascular events after an acute gout flare had not previously been studied. In a case-control study that included over 62,500 patients with gout in a longitudinal primary care database, of whom nearly 10,500 experienced a cardiovascular event (ie, stroke or myocardial infarction), acute gout flare was associated with increased risk of a cardiovascular event in the next 0 to 60 days (adjusted odds ratio [aOR] 1.93) and 61 to 120 days (aOR 1.57) [1]. These findings highlight the importance of managing cardiovascular risk factors among patients with gout. (See "Lifestyle modification and other strategies to reduce the risk of gout flares and progression of gout", section on 'Treatment of comorbidities'.)


Trial of intravenous immune globulin for dermatomyositis (November 2022)

Intravenous immune globulin (IVIG) has been used in the treatment of dermatomyositis (DM) based on limited observational data and small randomized trials. In a new randomized trial of 95 patients with DM, the percentage of patients who achieved a response of at least minimal improvement based on a composite score of disease activity was higher among those who received IVIG compared with placebo (79 versus 44 percent) at 16 weeks [2]. IVIG was associated with more adverse events, including thromboembolic events. Based on these results, the US Food and Drug Administration approved IVIG for the treatment of adults with dermatomyositis. More data are needed to help determine the potential role of IVIG as first-line therapy for patients with DM. (See "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults", section on 'Intravenous immune globulin'.)


New NF-kB-mediated autoinflammatory disease (ROSAH syndrome) (November 2022)

Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache (ROSAH) syndrome is an autosomal dominant disorder caused by gain-of-function heterozygous missense variants in the alpha kinase 1 gene (ALPK1). A recent study confirmed that ROSAH is an autoinflammatory disorder mediated by enhanced nuclear factor kappa B (NF-kB) signaling [3]. In this small case series, immunomodulation with anticytokine therapy was associated with improved autoinflammatory disease manifestations including fatigue, headache, and arthralgia, and also intraocular inflammation in those who did not have advanced retinal disease. Additional studies are needed to determine the best choice of therapy and whether earlier treatment can prevent development of disease manifestations. (See "Autoinflammatory diseases mediated by NFkB and/or aberrant TNF activity", section on 'ALPK1 gain-of-function defects (ROSAH syndrome)'.)


Phase 3 trial of olokizumab for rheumatoid arthritis (September 2022)

Olokizumab is an investigational monoclonal antibody that targets the interleukin-6 cytokine directly. A recent phase 3 trial compared olokizumab (dosed every two or four weeks), adalimumab (a tumor necrosis factor inhibitor), and placebo in 464 patients with rheumatoid arthritis (RA) receiving treatment with methotrexate [4]. At 12 weeks, the proportion of patients who achieved an American College of Rheumatology 20 response (≥20 percent fewer tender and swollen joints and ≥20 percent improvement in three of five other domains) was greater for olokizumab versus placebo and similar for olokizumab versus adalimumab. The incidence of serious adverse events was similar across the three groups. Larger and longer-term trials are needed to further evaluate the efficacy and safety of olokizumab in the treatment of RA. (See "Interleukin 6 inhibitors: Biology, principles of use, and adverse effects", section on 'Structure and mechanism of action of specific agents'.)

Add-on low-dose glucocorticoids in older patients with rheumatoid arthritis (August 2022)

Although short-term use of low-dose glucocorticoids is common in the management of rheumatoid arthritis (RA), evidence is conflicting regarding its efficacy and safety when used on a chronic basis. In a randomized trial of 451 patients with RA aged 65 years and older, the addition of prednisolone 5 mg daily to disease-modifying therapy resulted in lower measures of disease activity (0.37 points lower on a 10-point scale) and joint damage progression (1.7 points lower on a 10-point scale) compared with placebo after two years of follow-up [5]. However, patients in the prednisolone arm experienced more adverse events (60 versus 49 percent), which consisted mostly of nonserious infections. Thus, while some patients may experience modest benefit with add-on low-dose glucocorticoids, the lowest effective dose should be used to minimize harms, if it is not possible to discontinue glucocorticoid therapy. (See "Use of glucocorticoids in the treatment of rheumatoid arthritis", section on 'Efficacy of chronic use'.)

Methotrexate for prevention of rheumatoid arthritis (August 2022)

Various medical therapies have been evaluated for the prevention of rheumatoid arthritis (RA) among patients considered to be at high risk for developing clinically active disease. In the TREAT EARLIER trial that included 236 patients with arthralgias who were suspected of progressing to RA based on magnetic resonance imaging (MRI)-detected subclinical joint inflammation, patients who were randomly assigned to receive a one-year course of oral methotrexate had similar rates of developing clinical arthritis compared with those who took placebo (19 versus 18 percent, respectively) [6]. However, there were greater improvements in self-reported measures of physical function, pain, and morning stiffness, as well as MRI-detected joint inflammation, in the methotrexate-treated group, which supports the role of methotrexate as an effective disease-modifying treatment among patients in the early phases of the disease. (See "Epidemiology of, risk factors for, and possible causes of rheumatoid arthritis", section on 'Clinical trials examining preventive therapies'.)


Updated treatment guidelines for psoriatic arthritis (October 2022)

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has published updated guidelines to include newer therapeutic options for patients with psoriatic arthritis (PsA) that have become available [7]. The guidelines use a domain-based approach that includes recommendations for peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, and nail psoriasis. Important comorbidities and related conditions that may have a potential impact on treatment are also addressed. Our approach to the treatment of PsA is generally consistent with these guidelines. (See "Treatment of psoriatic arthritis", section on 'MTX use and efficacy'.)

Upadacitinib for nonradiographic axial spondyloarthritis (August 2022)

While janus kinase (JAK) inhibitors such as upadacitinib are effective in ankylosing spondylitis (AS), their role in nonradiographic axial spondyloarthritis (nr-axSpA), a potentially earlier form of AS, remains unclear. In a randomized trial in 313 patients with active nr-axSpA, upadacitinib resulted in a higher Assessment of SpondyloArthritis International Society 40 percent (ASAS40) response rate than placebo at 14 weeks (45 versus 23 percent) [8]. Rates of adverse events were similar between the two groups. These findings support the use of upadacitinib for patients with nr-axSpA. (See "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Upadacitinib'.)


Trial of litifilimab for systemic lupus erythematosus (September 2022)

Blood dendritic cell antigen 2 (BDAC2) is a receptor that is expressed exclusively on plasmacytoid dendritic cells, which are thought to play a role in the pathogenesis of systemic lupus erythematosus (SLE). In a phase 2 trial including 132 patients with SLE, arthritis, and active skin disease, patients who were randomly assigned to receive litifilimab (a subcutaneously injected monoclonal antibody that binds BDAC2) demonstrated a greater reduction from baseline in the number of swollen and tender joints compared with the placebo group at 24 weeks (mean difference -3.4) [9]. Serious adverse effects were reported in 5 versus 11 percent of the litifilimab and placebo groups, respectively. Additional longer term data are needed to determine the safety and efficacy of litifilimab for the treatment of SLE. (See "Overview of the management and prognosis of systemic lupus erythematosus in adults", section on 'Agents under investigation'.)

Oral tacrolimus versus intravenous cyclophosphamide for lupus nephritis (August 2022)

Calcineurin inhibitors (CNIs) in combination with mycophenolate (MMF) have been used for initial therapy for lupus nephritis (LN) as an alternative to cyclophosphamide, but the efficacy of CNIs without MMF remains unclear. In a trial that randomly assigned over 300 patients with LN to oral tacrolimus or intravenous cyclophosphamide for 24 weeks, the rate of complete response was higher in the tacrolimus group (50 versus 36 percent) [10]. Rates of serious treatment-emergent adverse events were lower in the tacrolimus group; however, patients receiving tacrolimus had an increase in serum creatinine that was sustained for the duration of the trial. Although additional longer-term studies are needed to confirm these findings, we continue to suggest glucocorticoids in combination with MMF or cyclophosphamide alone for initial therapy of focal or diffuse LN. (See "Lupus nephritis: Initial and subsequent therapy for focal or diffuse lupus nephritis", section on 'Calcineurin inhibitors plus mycophenolate'.)


Role of tocilizumab in patients with polymyalgia rheumatica (October 2022)

While relatively low doses of glucocorticoids are the primary treatment for polymyalgia rheumatica (PMR), interest remains in identifying an effective steroid-sparing agent. In a randomized trial of 100 patients with steroid-dependent PMR, patients who received adjunctive intravenous tocilizumab were more likely to achieve a combined endpoint of lower disease activity score and reduced steroid requirement at 24 weeks (67 versus 31 percent) [11]. Infections were the most frequent adverse events, occurring in 47 and 39 percent of the tocilizumab and placebo groups, respectively. Additional data are needed to confirm these findings and determine the benefits and safety of adjunctive tocilizumab use for PMR. The routine use of steroid-sparing therapies, including adjunctive tocilizumab, is not recommended for patients with PMR. (See "Treatment of polymyalgia rheumatica", section on 'Limited role for glucocorticoid-sparing therapies'.)

Rituximab for adults >75 years old with ANCA-associated vasculitis (August 2022)

Rituximab has been shown to be efficacious in patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), but randomized trials included few patients who were 75 years or older. An observational study of 93 adults aged >75 years with GPA or MPA found that rituximab for induction and/or maintenance therapy was associated with remission in most patients and low rates of relapse [12]. However, rates of serious infection were high (46.6 per 100 patient-years) among patients receiving rituximab for induction therapy. These findings support the use of rituximab in patients 75 years old but highlight the risk of serious infections in this patient population. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Induction and maintenance therapy", section on 'Induction therapy'.)


CDC updates opioid prescribing guidelines (November 2022)

The United States Centers for Disease Control and Prevention (CDC) has published a new guideline for prescribing opioids for acute, subacute, and chronic pain, updating their 2016 guideline (table 1). The guideline is intended for clinicians who prescribe opioids to outpatients ≥18 years of age and does not apply to pain related to sickle cell disease, cancer, palliative care, or end of life care [13]. (See "Use of opioids in the management of chronic non-cancer pain", section on 'Opioid therapy in the context of the opioid epidemic'.)

Perioperative management of medications for systemic rheumatic diseases around elective total hip or knee arthroplasty (September 2022)

The American College of Rheumatology and the American Association of Hip and Knee Surgeons have recently updated their recommendations for the perioperative management of medications for patients with systemic rheumatic diseases undergoing elective total hip or knee arthroplasty [14,15]. The guidelines include newer immunosuppressive agents as well as updated recommendations regarding when to continue, withhold, and restart these medications. Our approach to perioperative medication management is generally consistent with these guidelines. (See "Preoperative evaluation and perioperative management of patients with rheumatic diseases", section on 'Medication management'.)

Perioperative management of biologic disease-modifying antirheumatic drugs (September 2022)

There is limited evidence to inform the optimal timing of use for biologic disease-modifying antirheumatic drugs (DMARDs) in the perioperative period among patients with systemic rheumatic diseases. In a meta-analysis of cohort studies including over 7300 patients on biologic DMARDs for systemic rheumatic diseases who were undergoing surgery, patients who continued biologics did not appear to be at an increased risk for surgical site infection or delayed wound healing [16]. Stopping biologics prior to surgery, however, was associated with higher rates of disease flares (26 versus 7 percent). These findings are limited by the retrospective and heterogenous nature of the evidence. Our general approach to patients on biologic DMARDs undergoing elective surgery is to withhold the medication at the end of the dosing cycle if disease activity permits. (See "Preoperative evaluation and perioperative management of patients with rheumatic diseases", section on 'Biologic DMARDs'.)

Steroid injection for Achilles tendinopathy (August 2022)

Debate continues about the appropriate role for glucocorticoid injection in the treatment of chronic tendinopathy. In a blinded, randomized trial of 100 patients with Achilles tendinopathy causing symptoms for a minimum of three months and who received exercise therapy, those assigned to glucocorticoid injection experienced greater functional and symptomatic improvement at three and six months compared with patients given placebo injections [17]. However, no significant difference in functional outcomes or tendon thickness was noted at 12 or 24 months. These findings, which are consistent with other studies, support our limited use of glucocorticoid injections as adjunct therapy early in the treatment of chronic tendinopathy. Such injections may be most helpful for patients with persistent pain who are unable to participate in physical therapy. (See "Achilles tendinopathy and tendon rupture", section on 'Local injection therapies'.)

Ultrasound- versus landmark-guided technique for joint aspirations (July 2022)

Although some joint aspirations may be performed using anatomic landmarks, the use of ultrasound guidance has been shown to improve accuracy of needle placement in previous studies. In a randomized trial including 44 patients presenting to an emergency department with a suspected moderate-size joint effusion involving the elbow, wrist, or ankle, a greater number of successful aspirations were performed with ultrasound guidance compared with landmark-guided aspirations (94 versus 60 percent) [18]. Notably, of the 14 landmark-guided aspirations for which arthrocentesis was initially unsuccessful, 8 of the patients had no effusion when subsequently evaluated with ultrasonography. This small study supports the use of ultrasound guidance to improve the success rates of arthrocentesis of medium-sized joints. (See "Musculoskeletal ultrasonography: Guided injection and aspiration of joints and related structures", section on 'Accuracy of needle placement'.)

  1. Cipolletta E, Tata LJ, Nakafero G, et al. Association Between Gout Flare and Subsequent Cardiovascular Events Among Patients With Gout. JAMA 2022; 328:440.
  2. Aggarwal R, Charles-Schoeman C, Schessl J, et al. Trial of Intravenous Immune Globulin in Dermatomyositis. N Engl J Med 2022; 387:1264.
  3. Kozycki CT, Kodati S, Huryn L, et al. Gain-of-function mutations in ALPK1 cause an NF-κB-mediated autoinflammatory disease: functional assessment, clinical phenotyping and disease course of patients with ROSAH syndrome. Ann Rheum Dis 2022; 81:1453.
  4. Smolen JS, Feist E, Fatenejad S, et al. Olokizumab versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med 2022; 387:715.
  5. Boers M, Hartman L, Opris-Belinski D, et al. Low dose, add-on prednisolone in patients with rheumatoid arthritis aged 65+: the pragmatic randomised, double-blind placebo-controlled GLORIA trial. Ann Rheum Dis 2022; 81:925.
  6. Krijbolder DI, Verstappen M, van Dijk BT, et al. Intervention with methotrexate in patients with arthralgia at risk of rheumatoid arthritis to reduce the development of persistent arthritis and its disease burden (TREAT EARLIER): a randomised, double-blind, placebo-controlled, proof-of-concept trial. Lancet 2022; 400:283.
  7. Coates LC, Soriano ER, Corp N, et al. Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA): updated treatment recommendations for psoriatic arthritis 2021. Nat Rev Rheumatol 2022; 18:465.
  8. Deodhar A, Van den Bosch F, Poddubnyy D, et al. Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2022; 400:369.
  9. Furie RA, van Vollenhoven RF, Kalunian K, et al. Trial of Anti-BDCA2 Antibody Litifilimab for Systemic Lupus Erythematosus. N Engl J Med 2022; 387:894.
  10. Zheng Z, Zhang H, Peng X, et al. Effect of Tacrolimus vs Intravenous Cyclophosphamide on Complete or Partial Response in Patients With Lupus Nephritis: A Randomized Clinical Trial. JAMA Netw Open 2022; 5:e224492.
  11. Devauchelle-Pensec V, Carvajal-Alegria G, Dernis E, et al. Effect of Tocilizumab on Disease Activity in Patients With Active Polymyalgia Rheumatica Receiving Glucocorticoid Therapy: A Randomized Clinical Trial. JAMA 2022; 328:1053.
  12. Thietart S, Karras A, Augusto JF, et al. Evaluation of Rituximab for Induction and Maintenance Therapy in Patients 75 Years and Older With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. JAMA Netw Open 2022; 5:e2220925.
  13. Dowell D, Ragan KR, Jones CM, et al. CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022. MMWR Recomm Rep 2022; 71:1.
  14. Goodman SM, Springer BD, Chen AF, et al. 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. Arthritis Care Res (Hoboken) 2022; 74:1399.
  15. Goodman SM, Springer BD, Chen AF, et al. 2022 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. Arthritis Rheumatol 2022; 74:1464.
  16. van Duren BH, Wignall A, Goodman S, et al. The Effect of Perioperative Biologic Disease-Modifying Anti-Rheumatic Drugs on the Risk of Postoperative Complications: Surgical Site Infection, Delayed Wound Healing, and Disease Flares Following Orthopaedic Surgical Procedures. J Bone Joint Surg Am 2022; 104:1116.
  17. Johannsen F, Olesen JL, Øhlenschläger TF, et al. Effect of Ultrasonography-Guided Corticosteroid Injection vs Placebo Added to Exercise Therapy for Achilles Tendinopathy: A Randomized Clinical Trial. JAMA Netw Open 2022; 5:e2219661.
  18. Gibbons RC, Zanaboni A, Genninger J, Costantino TG. Ultrasound-versus landmark-guided medium-sized joint arthrocentesis: A randomized clinical trial. Acad Emerg Med 2022; 29:159.
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