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Psoriatic arthritis is a chronic debilitating autoimmune condition, and when diagnosed in patients before the age of eighteen, it is considered pediatric polyarticular juvenile idiopathic arthritis. Juvenile idiopathic arthritis is an umbrella term used to describe different inflammatory arthropathies that are diagnosed in children under the age of sixteen with symptoms lasting at least six weeks. Psoriatic arthritis differs from other arthropathies, particularly in its cutaneous involvement. The disease can be monoarticular or polyarticular, but a few distinguishing characteristics include radiographic findings of the “pencil-in-cup deformity” and scaly, white skin lesions that often bleed when scratched.
- golimumab
- juvenile idiopathic arthritis
- psoriatic arthritis
- autoimmune inflammatory diseases
1. Psoriatic Juvenile Idiopathic Arthritis
Psoriatic juvenile idiopathic arthritis (psJIA) is a subtype of JIA that is characterized by arthritis and psoriasis. International League of Associations for Rheumatology (ILAR) criteria also include arthritis and at least two of the following findings: nail pitting or onycholysis; dactylitis; and psoriasis in a first-degree relative, excluding other causes of joint pain [1][2]. PsJIA is a chronic autoimmune disease that affects children and adolescents, and it accounts for 5–8% of all juvenile idiopathic arthritis (JIA) cases [3][4] with a total calculated incidence of roughly three per million [3]. In this section, researchers will discuss the epidemiology, symptoms, and pathogenesis of psJIA.
PsJIA peaks occur bimodally and are broken down into two subgroups based on age. The early-onset group typically presents between ages 2 and 3 with a female predominance, ANA positivity, and chronic uveitis, mostly affecting the joints of the wrists and small joints of the hands and feet [5]. This is in comparison with the older subset, which typically presents between ages 8 and 12, where the patients are typically male, have HLA-B27 positivity, and have features of spondyloarthritis (SpA), such as axial pain and enthesitis [4][5]. Both subgroups typically present with dactylitis and psoriatic changes.
PsJIA can present with a variety of clinical manifestations depending on the number of joints inflamed. Most often, joint involvement occurs years before psoriasis and can mimic other forms of JIA [1]. The extent of joint involvement in arthritis can range from small-joint arthritis that affects both sides equally to large-joint involvement in the lower extremities that is asymmetrical and may develop into polyarthritis resembling rheumatoid arthritis. Notably, the presence of distal interphalangeal (DIP) joint involvement is highly suggestive of psJIA [2]. Dactylitis is another hallmark feature of psJIA, which presents as a sausage-like swelling of the fingers or toes resulting from MCP, PIP, and DIP joint involvement. Enthesitis, sacroiliitis, and spondylitis can also occur in psJIA. Psoriatic plaques often appear on the extensor surfaces of joints, hairy skin, the umbilicus, and the perineum. Nail dystrophy, onycholysis, and pitting are also common in psJIA [2]. In addition, ANA is present in a significant proportion of patients with psJIA, and HLA-B27 is present in about 30% of patients [6]. The diagnosis of psJIA is made based on clinical criteria, and laboratory tests are not specific to the disease.
Although the exact cause of psJIA is unknown, it has a complex etiology that involves both genetic and environmental factors. Several genetic loci have been shown to be associated with psJIA, including HLA-B27 (older subset) and HLA-DR5 (younger subset) [5]. Alterations in both the adaptive and innate immune systems are also thought to play a key role. JPsA is considered an autoimmune disease, and environmental triggers such as infections, trauma, antibiotics, etc., can lead to synovial inflammation [3]. Furthermore, faulty B cell tolerance has been proposed as a cause, as the autoantibodies antinuclear antibody, rheumatoid factor, and anti-citrullinated protein antibodies are produced by B cells [3]. Moreover, disturbances in the gut microbiome have been found to play a role in the pathogenesis of JIA, especially in those in the older subset [3][5].
2. Safety and Efficacy of Golimumab in Rheumatologic Diseases
Over the past few years, extensive studies have been performed to investigate the safety and efficacy of IV and subcutaneous (sc) golimumab in adults ages 18–83 [7][8][9][10]. The GO-AFTER trial was one of the earliest studies examining the efficacy of golimumab as a treatment for active rheumatoid arthritis. This was a multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial that enrolled 461 patients with active rheumatoid arthritis to receive 50 mg of sc golimumab, 100 mg of sc golimumab, or a placebo. In total, 35% of patients on 50 mg of golimumab and 38% of patients on 100 mg of golimumab achieved ACR20 at week 14, while only 18% of placebo-treated patients reached ACR20. Over 16 weeks, serious adverse events were seen in 5% of 50 mg golimumab-treated patients, 3% of 100 mg golimumab-treated patients, and 7% of placebo-treated patients [11]. Additional trials further examined the efficacy of golimumab as a treatment for other arthropathies. Notably, Kavanaugh et al. conducted the GO VIBRANT trial. This was a randomized, double-blind, placebo-controlled, phase III clinical trial. In total, 480 patients (239 controls, 241 on golimumab) with active psoriatic arthritis were randomly assigned to experimental groups to receive a placebo or 2 mg/kg of IV golimumab at weeks 0 and 4, and every 8 weeks after that. The results were analyzed using the American College of Rheumatology ≥ 20%, 50%, and 70% improvement criteria (ACR20/50/70). Evaluations at week 14 found that a greater percentage of golimumab patients reached ACR20/50/70 improvement criteria. Radiological progression was assessed using the Psoriasis Area and Severity Index ≥ 75% (PASI75) comparing baseline measurements to weeks 14 and 24 in the total modified Sharp/van der Heijede score (SHS). Experimental groups showed a greater mean change at week 14 and week 24 compared with the placebo group. Patients ≥ 18 with PsA for ≥6 months were included in the GO VIBRANT trial, with reported adverse effects including pleomorphic adenoma, myocardial infarction, pneumonia, abnormal liver function test result, neuritis, drug-induced liver injury (MTX-induced toxic hepatitis), and pustular psoriasis [9]. However, there was no remarkable difference in the number of adverse events between either group [9].
Over 52 weeks using a crossover design, the GO VIBRANT trial examined the long-term safety and efficacy of IV golimumab. Patients in the placebo group were crossed over to the golimumab treatment at week 24, with injections every 8 weeks until week 52. At week 52, the crossover group reached the same ACR20/50/70 improvements as the original golimumab group [8]. Further analysis of the GO VIBRANT trial examined health-related quality of life and work productivity by examining the change from baseline in the EuroQol-5 dimension-5 level (EQ-5d-5L) index and the Work Limitations Questionnaire (WLQ). Evaluations at week 24 found marked improvements in the golimumab group versus the placebo. Re-examinations at week 52 found the crossover group showed a change from baseline similar to the original golimumab group [8]. This crossover study showed a rapid and sustained improvement in patients with psoriatic arthritis treated with IV golimumab, with no new safety risks.
Similar crossover studies have examined the role of IV golimumab in ankylosing spondylitis (GO-ALIVE) and rheumatoid arthritis (GO-FURTHER). An additional methotrexate treatment was required in the rheumatoid arthritis study and accepted in the ankylosing spondylitis and psoriatic arthritis trials. A large study pooled the safety results of all three clinical trials and found that, while IV golimumab had a similar safety profile to other TNF inhibitors, cotreatment with methotrexate was associated with increased alanine transaminase levels and an increased incidence of serious infections [7]. The GO-VIVA trial used 127 patients between 2 and 8 years old with active polyarticular course-JIA despite ≥2 months of methotrexate treatment. In total, 84%, 80%, 70%, and 47% of patients treated with IV golimumab 80 mg/m2 reached JIA ACR 30, 50, 70, and 90, respectively. GO-VIVA made no reference to use in children less than two. Serious infections were reported in 6% of patients [11]. These results indicate no increase in safety risks for IV golimumab and a promising role as an effective therapy for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
A 2020 phase III, randomized, placebo-controlled trial investigated the effects of IV golimumab on patients with active psoriatic arthritis (PsA). The study found that patients receiving golimumab, as compared with a placebo, had continued improvements in both joint arthritis and skin disease after 1 year. Measurements were made using the American College of Rheumatology (ACR) ≥ 20%, 50%, and 70% improvement criteria (ACR20/50/70), as well as the Psoriasis Area and Severity Index ≥ 75% criteria (PASI75). Radiographic progression was assessed using the PsA-modified Sharp/van der Heijde score (SHS). Overall, these data suggest that golimumab improves skin and joint outcomes in patients with active PsA and that the safety profile was like that of other anti-tumor necrosis factor (TNF) agents [10]. A 2021 phase III, open-label, single-arm, international study evaluated the pharmacokinetics and safety of IV golimumab in children. ACR improvement criteria were noted. Steady-state trough concentrations and AUCs were similar to those of adult patients [11]. A 2021 retrospective study investigated the efficacy of golimumab in treating JIA patients with uveitis who stopped responding to adalimumab, the drug of choice in treating uveitis. The study found that golimumab was successful in treating all eight patients who had stopped responding to adalimumab. However, the two patients who never responded to adalimumab also did not respond to golimumab. Overall, this small study demonstrated that golimumab can be effective in treating patients who lose responsiveness to adalimumab for uveitis. A 2018 randomized, double-blind, placebo-controlled withdrawal trial explored the safety and efficacy of subcutaneous golimumab in children with active polyarticular-course juvenile idiopathic arthritis (polyJIA). The study found that, although golimumab showed significant improvement in ACR30/50/70/90, the primary endpoints, JIA flare rates, and remission were not met, as they showed similar rates to the placebo (Table 1) [8][12][13][14].
Table 1. Clinical safety and efficacy systemic review.
| Author (Year) | Groups Studied and Intervention | Results and Findings | Conclusions |
|---|---|---|---|
| Study 1: Husni [8] |
Adults ≥ 18 with active PsA for ≥ 6 months were given either 2 mg/kg IV golimumab or placebo at weeks 0 and 4 and every 8 weeks. | A greater percentage of patients in the treatment group reached ACR20, ACR50, and ACR70. Radiographic progression was also significantly improved. | Golimumab was found to be significantly effective in treating patients with active PsA after 1 year. Although there were increased AEs, they were like those of other anti-TNF agents. |
| Study 2: Ruperto [12] | Active pc-JIA, ages 2–17, 80 mg/m2 golimumab. Weeks 0 and 4 and weeks 8 through 52, with methotrexate after week 28. |
JIA ACR 30, 50, 70, 90 response rates for 84%, 80%, 70%, and 47% at week 28 and through to week 52; 6% with serious infections, including one death caused by sepsis. | Golimumab was effective in treating pediatric patients with pc-JIA. Serious AEs (infections) occurred in 6%., with one death. |
| Study 3: Lanz [13] |
Ten (seventeen eyes) females ages 7–21 with active JIA-associated uveitis refractory to adalimumab received golimumab. | Eight patients with loss of response all responded to golimumab. The 2 initial non-responders did not respond to golimumab. | Golimumab is therapeutic in patients with loss of response to adalimumab, but those not responding to adalimumab did not respond to golimumab. |
| Study 4: Brunner [14] | In total, 173 active polyJIA patients ages 2–17 were treated with golimumab or a placebo. | After 48 weeks, there was no difference in the number of JIA flareups and clinical remission between golimumab and placebo. Golimumab was safe and tolerated well. | Golimumab resulted in significant improvement in patients with active polyJIA; however, primary endpoints were not met. |
This entry is adapted from the peer-reviewed paper 10.3390/life13071601
References
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- Barut, K.; Adroviïc, A.; Şahiïn, S.; Kasapçopur, Ö. Juvenile Idiopathic Arthritis. Balk. Med. J. 2017, 34, 90–101.
- Moura, R.A.; Fonseca, J.E. B Cells on the Stage of Inflammation in Juvenile Idiopathic Arthritis: Leading or Supporting Actors in Disease Pathogenesis? Front. Med. 2022, 9, 851532.
- Ogdie, A.; Weiss, P. The Epidemiology Psoriatic Arthritis. Rheum. Dis. Clin. North Am. 2015, 41, 545–568.
- Stoll, M.L.; Punaro, M. Psoriatic juvenile idiopathic arthritis: A tale of two subgroups. Curr. Opin. Rheumatol. 2011, 23, 437–443.
- Ravelli, A.; Consolaro, A.; Schiappapietra, B. The Conundrum of Juvenile Psoriatic Arthritis. Clin. Exp. Rheumatol. 2015, 33 (Suppl. 93), S40–S43. Available online: https://www.clinexprheumatol.org/abstract.asp?a=9980 (accessed on 3 May 2023).
- Husni, M.E.; Deodhar, A.; Schwartzman, S.; Chakravarty, S.D.; Hsia, E.C.; Leu, J.H.; Zhou, Y.; Lo, K.H.; Kavanaugh, A. Pooled Safety Results across Phase 3 Randomized Trials of Intravenous Golimumab in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis. Thromb. Haemost. 2022, 24, 73.
- Husni, M.E.; Kavanaugh, A.; Murphy, F.; Rekalov, D.; Harrison, D.D.; Kim, L.; Lo, K.H.; Leu, J.H.; Hsia, E.C. Efficacy and Safety of Intravenous Golimumab Through One Year in Patients with Active Psoriatic Arthritis. Arthritis Care Res. 2019, 72, 806–813.
- Kavanaugh, A.; Husni, M.E.; Harrison, D.D.; Kim, L.; Lo, K.H.; Leu, J.H.; Hsia, E.C. Safety and Efficacy of Intravenous Golimumab in Patients with Active Psoriatic Arthritis: Results through Week Twenty-Four of the GO-VIBRANT Study. Arthritis Rheumatol. 2017, 69, 2151–2161.
- Ogdie, A.; Walsh, J.A.; Chakravarty, S.D.; Peterson, S.; Lo, K.H.; Kim, L.; Li, N.; Hsia, E.C.; Chan, E.K.H.; Kavanaugh, A.; et al. The Effect of Intravenous Golimumab on Health-Related Quality of Life and Work Productivity in Patients with Active Psoriatic Arthritis: Results of the Phase 3 GO-VIBRANT Trial. Clin. Rheumatol. 2021, 40, 3667–3677.
- Smolen, J.S.; Kay, J.; Doyle, M.K.; Landewé, R.; Matteson, E.L.; Wollenhaupt, J.; Gaylis, N.; Murphy, F.T.; Neal, J.S.; Zhou, Y.; et al. Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): A multicentre, randomised, double-blind, placebo-controlled, phase III trial. Lancet 2009, 374, 210–221, Erratum in Lancet 2009, 374, 1422.
- Ruperto, N.; I Brunner, H.; Pacheco-Tena, C.; Louw, I.; Vega-Cornejo, G.; Spindler, A.J.; Kingsbury, D.J.; Schmeling, H.; Borzutzky, A.; Cuttica, R.; et al. Open-label phase 3 study of intravenous golimumab in patients with polyarticular juvenile idiopathic arthritis. Rheumatology 2021, 60, 4495–4507.
- Lanz, S.; Seidel, G.; Skrabl-Baumgartner, A. Golimumab in juvenile idiopathic arthritis-associated uveitis unresponsive to Adalimumab. Pediatr. Rheumatol. Online J. 2021, 19, 132.
- Brunner, H.I.; Ruperto, N.; Tzaribachev, N.; Horneff, G.; Chasnyk, V.G.; Panaviene, V.; Abud-Mendoza, C.; Reiff, A.; Alexeeva, E.; Rubio-Pérez, N.; et al. Subcutaneous golimumab for children with active polyarticular-course juvenile idiopathic arthritis: Results of a multicentre, double-blind, randomized-withdrawal trial. Ann. Rheum. Dis. 2018, 77, 21–29.
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