Commentary: Targeted Therapies in PsA, September 2024

The question of whether effective targeted therapies for psoriasis reduce the incidence or "prevent" psoriatic arthritis (PsA) has increasingly become a topic of interest. Also of interest is whether there are differences between different drug classes for treating psoriasis and PsA. To evaluate whether there is a difference between patients treated with interleukin (IL)-23 vs IL-12/23 inhibitors, Tsai and colleagues conducted a retrospective cohort study that included the propensity score–matched data of patients with psoriasis from the TriNetX database who were treated with either IL-23 inhibitors (n = 2142) or IL-12/23 inhibitors (n = 2142). Patients treated with IL-23 inhibitors vs IL-12/23 inhibitors demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812). Given the many drawbacks of administrative database-based retrospective studies, I would ideally like to see prospective studies conducted to evaluate the differential risk for PsA between targeted therapies for psoriasis. However, patients can be assured that the beneficial effect, if any, is likely to be similar between these two drug classes in regard to PsA prevention.

One important question when treating patients with PsA with biologic therapies is whether treatment with methotrexate needs to be continued. In a post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) that included patients with PsA who were biologic-naive (n = 852) or had an incomplete response to a tumor necrosis factor (TNF) inhibitor (n = 400), McInnes and colleagues evaluated the efficacy and safety of bimekizumab in patients with active PsA with or without concomitant methotrexate treatment at baseline. They demonstrated that through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNF inhibitor ~48-56%) and minimal disease activity (biologic-naive ~55%; TNF inhibitor ~47%). Thus, bimekizumab demonstrated similar sustained efficacy for 52 weeks, regardless of concomitant methotrexate use. Therefore, concomitant treatment with methotrexate may not be necessary when treating PsA patients with bimekizumab.

Nonpharmacologic interventions, such as diet and exercise, are likely to be of benefit to PsA patients, but studies on such therapies are lacking. In a cross-sectional study that enrolled 279 patients with PsA and 76 patients with psoriasis, Katsimbri and colleagues showed that patients reporting high vs low levels of exercise had significantly lower median values of Disease Activity Index for PsA and erythrocyte sedimentation rate, and fewer tender and swollen joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index and body surface area affected by psoriasis. Thus, exercise and a Mediterranean diet may improve disease activity outcomes in PsA, and may be an important adjunct to immunomodulatory therapy. However, prospective interventional trials are required.

Finally, a study evaluated whether the initiation of targeted therapies, such as biologics, led to a decrease in the use of other arthritis-related treatments and healthcare use in PsA. Using data from the French health insurance database, Pina Vegas and colleagues evaluated the difference in the proportion of users of associated treatments, hospitalizations, and sick leaves between 6 months before and 3-9 months after treatment initiation. In a cohort of 9793 patients, they found that first-line targeted therapy significantly reduced the use of nonsteroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), and mood disorder treatments (−2%), and lowered the rate of hospitalizations (−12%) and sick leave (−4%; all P < 10^-4). TNF inhibitors showed greater reductions in NSAID and prednisone use compared with IL-17 inhibitors, with similar outcomes for IL-12/23 inhibitors.

The question of whether effective targeted therapies for psoriasis reduce the incidence or "prevent" psoriatic arthritis (PsA) has increasingly become a topic of interest. Also of interest is whether there are differences between different drug classes for treating psoriasis and PsA. To evaluate whether there is a difference between patients treated with interleukin (IL)-23 vs IL-12/23 inhibitors, Tsai and colleagues conducted a retrospective cohort study that included the propensity score–matched data of patients with psoriasis from the TriNetX database who were treated with either IL-23 inhibitors (n = 2142) or IL-12/23 inhibitors (n = 2142). Patients treated with IL-23 inhibitors vs IL-12/23 inhibitors demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812). Given the many drawbacks of administrative database-based retrospective studies, I would ideally like to see prospective studies conducted to evaluate the differential risk for PsA between targeted therapies for psoriasis. However, patients can be assured that the beneficial effect, if any, is likely to be similar between these two drug classes in regard to PsA prevention.

One important question when treating patients with PsA with biologic therapies is whether treatment with methotrexate needs to be continued. In a post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) that included patients with PsA who were biologic-naive (n = 852) or had an incomplete response to a tumor necrosis factor (TNF) inhibitor (n = 400), McInnes and colleagues evaluated the efficacy and safety of bimekizumab in patients with active PsA with or without concomitant methotrexate treatment at baseline. They demonstrated that through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNF inhibitor ~48-56%) and minimal disease activity (biologic-naive ~55%; TNF inhibitor ~47%). Thus, bimekizumab demonstrated similar sustained efficacy for 52 weeks, regardless of concomitant methotrexate use. Therefore, concomitant treatment with methotrexate may not be necessary when treating PsA patients with bimekizumab.

Nonpharmacologic interventions, such as diet and exercise, are likely to be of benefit to PsA patients, but studies on such therapies are lacking. In a cross-sectional study that enrolled 279 patients with PsA and 76 patients with psoriasis, Katsimbri and colleagues showed that patients reporting high vs low levels of exercise had significantly lower median values of Disease Activity Index for PsA and erythrocyte sedimentation rate, and fewer tender and swollen joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index and body surface area affected by psoriasis. Thus, exercise and a Mediterranean diet may improve disease activity outcomes in PsA, and may be an important adjunct to immunomodulatory therapy. However, prospective interventional trials are required.

Finally, a study evaluated whether the initiation of targeted therapies, such as biologics, led to a decrease in the use of other arthritis-related treatments and healthcare use in PsA. Using data from the French health insurance database, Pina Vegas and colleagues evaluated the difference in the proportion of users of associated treatments, hospitalizations, and sick leaves between 6 months before and 3-9 months after treatment initiation. In a cohort of 9793 patients, they found that first-line targeted therapy significantly reduced the use of nonsteroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), and mood disorder treatments (−2%), and lowered the rate of hospitalizations (−12%) and sick leave (−4%; all P < 10^-4). TNF inhibitors showed greater reductions in NSAID and prednisone use compared with IL-17 inhibitors, with similar outcomes for IL-12/23 inhibitors.

The question of whether effective targeted therapies for psoriasis reduce the incidence or "prevent" psoriatic arthritis (PsA) has increasingly become a topic of interest. Also of interest is whether there are differences between different drug classes for treating psoriasis and PsA. To evaluate whether there is a difference between patients treated with interleukin (IL)-23 vs IL-12/23 inhibitors, Tsai and colleagues conducted a retrospective cohort study that included the propensity score–matched data of patients with psoriasis from the TriNetX database who were treated with either IL-23 inhibitors (n = 2142) or IL-12/23 inhibitors (n = 2142). Patients treated with IL-23 inhibitors vs IL-12/23 inhibitors demonstrated no significant difference in the risk for PsA (hazard ratio 0.96; P = .812) and cumulative incidence of PsA (P = .812). Given the many drawbacks of administrative database-based retrospective studies, I would ideally like to see prospective studies conducted to evaluate the differential risk for PsA between targeted therapies for psoriasis. However, patients can be assured that the beneficial effect, if any, is likely to be similar between these two drug classes in regard to PsA prevention.

One important question when treating patients with PsA with biologic therapies is whether treatment with methotrexate needs to be continued. In a post hoc analysis of phase 3 trials (BE OPTIMAL, BE COMPLETE, and BE VITAL) that included patients with PsA who were biologic-naive (n = 852) or had an incomplete response to a tumor necrosis factor (TNF) inhibitor (n = 400), McInnes and colleagues evaluated the efficacy and safety of bimekizumab in patients with active PsA with or without concomitant methotrexate treatment at baseline. They demonstrated that through week 52, nearly half of the patients receiving bimekizumab with or without methotrexate achieved a ≥50% improvement in American College of Rheumatology response (biologic-naive ~55%; TNF inhibitor ~48-56%) and minimal disease activity (biologic-naive ~55%; TNF inhibitor ~47%). Thus, bimekizumab demonstrated similar sustained efficacy for 52 weeks, regardless of concomitant methotrexate use. Therefore, concomitant treatment with methotrexate may not be necessary when treating PsA patients with bimekizumab.

Nonpharmacologic interventions, such as diet and exercise, are likely to be of benefit to PsA patients, but studies on such therapies are lacking. In a cross-sectional study that enrolled 279 patients with PsA and 76 patients with psoriasis, Katsimbri and colleagues showed that patients reporting high vs low levels of exercise had significantly lower median values of Disease Activity Index for PsA and erythrocyte sedimentation rate, and fewer tender and swollen joints. Similarly, high vs low adherence to the Mediterranean diet was associated with a lower Psoriasis Area and Severity Index and body surface area affected by psoriasis. Thus, exercise and a Mediterranean diet may improve disease activity outcomes in PsA, and may be an important adjunct to immunomodulatory therapy. However, prospective interventional trials are required.

Finally, a study evaluated whether the initiation of targeted therapies, such as biologics, led to a decrease in the use of other arthritis-related treatments and healthcare use in PsA. Using data from the French health insurance database, Pina Vegas and colleagues evaluated the difference in the proportion of users of associated treatments, hospitalizations, and sick leaves between 6 months before and 3-9 months after treatment initiation. In a cohort of 9793 patients, they found that first-line targeted therapy significantly reduced the use of nonsteroidal anti-inflammatory drugs (NSAID; −15%), prednisone (−9%), methotrexate (−15%), and mood disorder treatments (−2%), and lowered the rate of hospitalizations (−12%) and sick leave (−4%; all P < 10^-4). TNF inhibitors showed greater reductions in NSAID and prednisone use compared with IL-17 inhibitors, with similar outcomes for IL-12/23 inhibitors.