Clinical Edge Journal Scan Commentary: PsA June 2021

Several important studies on psoriatic arthritis (PsA) were published in the month of May 2021. Although, 50% of patients with PsA are women, many of them being in the child-beaing age, few studies have investigated pregnancy outcomes in women with psoriatic disease. Xie et al, report the results of their systematic review and meta-analysis of observational studies evaluating the impact of psoriasis and PsA on pregnancy outcomes. They retrieved 16 articles that met their study criteria. They demonstrate that pregnant women with psoriatic disease have significantly higher risk of adverse maternal outcomes (caesarean delivery, preterm birth, (pre)eclampsia, gestational diabetes, or gestational hypertension) compared with general population. However, no increased risk of fetal complications was observed. The authors recommend close monitoring of the mothers’ clinical status before and during pregnancy.

Despite availability of multiple targeted therapies, only about 60% of patients achieve a meaningful response to therapy in randomized trials and only a quarter of patients achieve a state of minimal disease activity. The assessment of musculoskeletal inflammation is heavily dependent on assessment of tender and swollen joints. However, whether tender or swollen joints, especially tender joints, truly reflect joint inflammation is a matter of debate. Felbo et al investigated the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and magnetic resonance imaging (MRI) in patients with active PsA. They found that tender joints poorly reflect intra- and periarticular inflammation assessed by imaging. The association between swollen joints and ultrasound and MRI assessed inflammation was stronger but still only low-to-moderate. The agreement between joint tenderness and imaging assessed inflammation was even weaker in patients with high overall pain scores, high disability scores, or nonerosive disease. Therefore, it is recommended that imaging be used to supplement clinical examination in patients with PsA and high overall pain, disability, and/or nonerosive disease.

With regard to PsA treatment, Rahman et al reported the pooled safety results through one year of two phase 3 trials with guselkumab in PsA. This drug inhibits IL-23, has proven efficacy in PsA and psoriasis, and was recently approved for the treatment of PsA. No active tuberculosis, opportunistic infections, or inflammatory bowel disease, and low rates of malignancy and major adverse cardiovascular events, were observed in guselkumab-treated patients. In another study, using data from 2 large US claims databases, MarketScan and Optum’s De-identified Clinformatics® Data Mart, Jin et al demonstrated that other biologics and apremilast were associated with 1.4- to 3-times higher risk of hospitalized serious infections in patients with psoriatic disease when compared with ustekinumab. Ustekinumab is a biologic agent that inhibits IL-12 and IL-23 and is approved for the treatment of psoriasis, PsA, and ulcerative colitis. The two studies speak to the safety of targeting IL-23 with biologics in psoriatic disease.

Finally, an exploratory, proof-of-concept study explored whether fecal microbiota transplantation (FMT) improves the signs and symptoms of PsA. Kragsnaes et al conducted a double-blind, parallel-group, placebo-controlled, superiority trial, randomly allocating adults with active PsA despite ongoing treatment with methotrexate to one gastroscopic-guided FMT (15 patients) or sham transplantation (16 patients) into the duodenum. Surprisingly, treatment failure occurred more frequently in the FMT group than in the sham group (9 [60%] vs 3 [19%]; risk ratio, 3.20; 95% CI 1.06 to 9.62; P = 0.018). Improvement in HAQ-DI favoured sham treatment. There was no difference in the proportion of ACR20 responders between groups. No serious adverse events were observed. This study highlights that such studies are feasible but indicates that such interventions may not provide significant benefit. Further investigations including careful selection of donors, patients and concomitant therapy is required.

Several important studies on psoriatic arthritis (PsA) were published in the month of May 2021. Although, 50% of patients with PsA are women, many of them being in the child-beaing age, few studies have investigated pregnancy outcomes in women with psoriatic disease. Xie et al, report the results of their systematic review and meta-analysis of observational studies evaluating the impact of psoriasis and PsA on pregnancy outcomes. They retrieved 16 articles that met their study criteria. They demonstrate that pregnant women with psoriatic disease have significantly higher risk of adverse maternal outcomes (caesarean delivery, preterm birth, (pre)eclampsia, gestational diabetes, or gestational hypertension) compared with general population. However, no increased risk of fetal complications was observed. The authors recommend close monitoring of the mothers’ clinical status before and during pregnancy.

Despite availability of multiple targeted therapies, only about 60% of patients achieve a meaningful response to therapy in randomized trials and only a quarter of patients achieve a state of minimal disease activity. The assessment of musculoskeletal inflammation is heavily dependent on assessment of tender and swollen joints. However, whether tender or swollen joints, especially tender joints, truly reflect joint inflammation is a matter of debate. Felbo et al investigated the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and magnetic resonance imaging (MRI) in patients with active PsA. They found that tender joints poorly reflect intra- and periarticular inflammation assessed by imaging. The association between swollen joints and ultrasound and MRI assessed inflammation was stronger but still only low-to-moderate. The agreement between joint tenderness and imaging assessed inflammation was even weaker in patients with high overall pain scores, high disability scores, or nonerosive disease. Therefore, it is recommended that imaging be used to supplement clinical examination in patients with PsA and high overall pain, disability, and/or nonerosive disease.

With regard to PsA treatment, Rahman et al reported the pooled safety results through one year of two phase 3 trials with guselkumab in PsA. This drug inhibits IL-23, has proven efficacy in PsA and psoriasis, and was recently approved for the treatment of PsA. No active tuberculosis, opportunistic infections, or inflammatory bowel disease, and low rates of malignancy and major adverse cardiovascular events, were observed in guselkumab-treated patients. In another study, using data from 2 large US claims databases, MarketScan and Optum’s De-identified Clinformatics® Data Mart, Jin et al demonstrated that other biologics and apremilast were associated with 1.4- to 3-times higher risk of hospitalized serious infections in patients with psoriatic disease when compared with ustekinumab. Ustekinumab is a biologic agent that inhibits IL-12 and IL-23 and is approved for the treatment of psoriasis, PsA, and ulcerative colitis. The two studies speak to the safety of targeting IL-23 with biologics in psoriatic disease.

Finally, an exploratory, proof-of-concept study explored whether fecal microbiota transplantation (FMT) improves the signs and symptoms of PsA. Kragsnaes et al conducted a double-blind, parallel-group, placebo-controlled, superiority trial, randomly allocating adults with active PsA despite ongoing treatment with methotrexate to one gastroscopic-guided FMT (15 patients) or sham transplantation (16 patients) into the duodenum. Surprisingly, treatment failure occurred more frequently in the FMT group than in the sham group (9 [60%] vs 3 [19%]; risk ratio, 3.20; 95% CI 1.06 to 9.62; P = 0.018). Improvement in HAQ-DI favoured sham treatment. There was no difference in the proportion of ACR20 responders between groups. No serious adverse events were observed. This study highlights that such studies are feasible but indicates that such interventions may not provide significant benefit. Further investigations including careful selection of donors, patients and concomitant therapy is required.

Several important studies on psoriatic arthritis (PsA) were published in the month of May 2021. Although, 50% of patients with PsA are women, many of them being in the child-beaing age, few studies have investigated pregnancy outcomes in women with psoriatic disease. Xie et al, report the results of their systematic review and meta-analysis of observational studies evaluating the impact of psoriasis and PsA on pregnancy outcomes. They retrieved 16 articles that met their study criteria. They demonstrate that pregnant women with psoriatic disease have significantly higher risk of adverse maternal outcomes (caesarean delivery, preterm birth, (pre)eclampsia, gestational diabetes, or gestational hypertension) compared with general population. However, no increased risk of fetal complications was observed. The authors recommend close monitoring of the mothers’ clinical status before and during pregnancy.

Despite availability of multiple targeted therapies, only about 60% of patients achieve a meaningful response to therapy in randomized trials and only a quarter of patients achieve a state of minimal disease activity. The assessment of musculoskeletal inflammation is heavily dependent on assessment of tender and swollen joints. However, whether tender or swollen joints, especially tender joints, truly reflect joint inflammation is a matter of debate. Felbo et al investigated the association between clinical joint tenderness and intra- and periarticular inflammation as assessed by ultrasound and magnetic resonance imaging (MRI) in patients with active PsA. They found that tender joints poorly reflect intra- and periarticular inflammation assessed by imaging. The association between swollen joints and ultrasound and MRI assessed inflammation was stronger but still only low-to-moderate. The agreement between joint tenderness and imaging assessed inflammation was even weaker in patients with high overall pain scores, high disability scores, or nonerosive disease. Therefore, it is recommended that imaging be used to supplement clinical examination in patients with PsA and high overall pain, disability, and/or nonerosive disease.

With regard to PsA treatment, Rahman et al reported the pooled safety results through one year of two phase 3 trials with guselkumab in PsA. This drug inhibits IL-23, has proven efficacy in PsA and psoriasis, and was recently approved for the treatment of PsA. No active tuberculosis, opportunistic infections, or inflammatory bowel disease, and low rates of malignancy and major adverse cardiovascular events, were observed in guselkumab-treated patients. In another study, using data from 2 large US claims databases, MarketScan and Optum’s De-identified Clinformatics® Data Mart, Jin et al demonstrated that other biologics and apremilast were associated with 1.4- to 3-times higher risk of hospitalized serious infections in patients with psoriatic disease when compared with ustekinumab. Ustekinumab is a biologic agent that inhibits IL-12 and IL-23 and is approved for the treatment of psoriasis, PsA, and ulcerative colitis. The two studies speak to the safety of targeting IL-23 with biologics in psoriatic disease.

Finally, an exploratory, proof-of-concept study explored whether fecal microbiota transplantation (FMT) improves the signs and symptoms of PsA. Kragsnaes et al conducted a double-blind, parallel-group, placebo-controlled, superiority trial, randomly allocating adults with active PsA despite ongoing treatment with methotrexate to one gastroscopic-guided FMT (15 patients) or sham transplantation (16 patients) into the duodenum. Surprisingly, treatment failure occurred more frequently in the FMT group than in the sham group (9 [60%] vs 3 [19%]; risk ratio, 3.20; 95% CI 1.06 to 9.62; P = 0.018). Improvement in HAQ-DI favoured sham treatment. There was no difference in the proportion of ACR20 responders between groups. No serious adverse events were observed. This study highlights that such studies are feasible but indicates that such interventions may not provide significant benefit. Further investigations including careful selection of donors, patients and concomitant therapy is required.