Arthritis Res Ther: efficacy and safety of Guselkumab and Adalimumab in the treatment of pustular osteitis and their effect on peripheral blood immunophenotype

Background: Palmoplantar impetigo (PPP) is a chronic, recurrent inflammatory skin disease characterized by the appearance of aseptic pustules following the formation of erythema and scaly vesicles
locally on the palms and soles of the feet.
About 10-45% of PPP cases are complicated by articular osteitis, called pustular osteitis (PAO).

PAO presents with various joint symptoms such as thoracic and costocleidoclavicular osteoarthritis, spondylitis, sacroiliitis, and peripheral arthritis
.

Patients with PPP are known to have elevated
serum tumor necrosis factor (TNF)-α.
Anti-TNF inhibitors have been used in the treatment of PPP; However, studies have shown that its efficacy is controversial and needs further verification
.
Guselkumab is a biologic agent that binds to the p19 subunit protein of interleukin (IL)-23 and selectively inhibits IL-23 signaling
.
Recent clinical studies have reported the efficacy
of guselkumab on PPP.
In Japan, since November 2018, the national health insurance system has covered guselkumab for the treatment of PPPs
that do not respond well to traditional treatments.
Although clinical studies have reported exploratory analyses of the efficacy of guselkumab in the treatment of PPP joint symptoms, its efficacy in real clinical practice has only been described in case reports and has not been fully verified
.

IL-12/T cofactor (Th) 1 and IL-23/Th17 cell axes have been reported to play an important role
in the pathogenesis of PPP and PAO.
Especially in skin lesions, activation of the IL-23/Th17 cell axis is thought to play a central role in the pathology of both diseases, and the expression of cytokines produced by Th17 cells such as IL-17A and IL-17F is significantly increased
in skin lesions.
However, peripheral blood immunophenotypes in patients with PAO have not been analyzed, and the effects of treatment on these phenotypes are unclear
.

Objective: In this study, we compared the efficacy and safety
of guselkuma and adalimumab for PAO.
In addition, we performed peripheral blood immunophenotyping to elucidate the immune background of PAO and analyze the impact of therapeutic drugs to validate the effectiveness of
phenotypes as therapeutic targets.

Methods: 100 mg with Guselkumab (Guselkumab group; N = 12) and Adalimumab 40 mg (Adalimumab group; n = 13)
。 Assess and compare arthritis disease activity, lesion activity, and patient-reported prognosis (PROs)
between the two groups.
To assess retention rates and adverse events
.
Both groups underwent comprehensive phenotyping of peripheral blood immune cells and compared the phenotypes
before and after treatment.

Results: At 6 months, arthritis disease activity and PROs were significantly improved
in both groups.
In the Guselkumab group, skin symptoms improved
significantly.
The 6-month duration rates in the Guselkumab and adalimumab groups were 91.
7% (11/12) and 69.
2% (9/13),
respectively.
Adverse events
occurred in 2/12 and 5/13 patients in the guselkuma group (16.
7%) and adalimumab group (38.
5%), respectively.
The peripheral blood immunophenotype showed that the proportion of activated T helper (Th) 1 cells in PAO patients was significantly lower than that in healthy control groups, while the proportion of activated Th17 cells in PAO patients was significantly higher than that of guselkumab, while the activation ratio of Th17 cells was significantly lower
after guselkumab treatment.

Figure Guselkumab
group (n = 12) compared with adalimumab group (n = 13) for 6 months of treatment.
A DAPSA-LDA responder rate (%)
.
B DAPSA-REM REACTION RATE
.
C PPPASI-50 responder rate (%)
.
D PPPASI-75 responder rate
.
E PPPASI-90 responder rate (%)
.
*P<0.
05, accurately tested
by Fisher-Price.
Abbreviations: PPPASI palmoplantar pustulosis regional severity index, psoriatic arthritis DAPSA disease activity, LDA disease activity is low, REM remission

Table 1 Effectiveness of use of guselkumab and adalimumab over 6 months by 8 factors

Table 2 Adverse events in the Guselkumab and Adalimumab groups

Table 3 Comparison of peripheral blood immunophenotypes of PAO (n=22), PsA (n=33), and hc (n=30).

Conclusion: Although Guselkumab and Adalimumab are equally effective in PAO, they have different
effects on immunophenotyping.

Original: eno M, Miyagawa I, Miyazaki Y,et al.
Efficacy and safety of guselkumab and adalimumab for pustulotic arthro-osteitis and their impact on peripheral blood immunophenotypes Arthritis Res Ther 2022 Oct 27; 24(1)