Article

Identifying risk factors associated with transition from cutaneous psoriasis to arthritic psoriasis remains a hot area of research. In a retrospective nested case-control study using the resources of the Rochester Epidemiology Project, Karmacharya et al¹ identified 164 patients with incident PsA between 2000 and 2017. Among the 158 total patients satisfying study criteria, 64 (41%) had concurrent psoriasis and PsA and 94 (59%) had onset of psoriasis before PsA. The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA. Early onset as well as severe psoriasis is associated with the HLA- C*06 allele as is longer psoriasis-PsA latency. Although not evaluated in this study, this genetic factor, or other factors such as detection bias, may underly these observations.

Once diagnosed, stratification of PsA severity is important for planning treatment. Towards this goal, Dubash et al² demonstrated that the presence of dactylitis indicates a more severe PsA phenotype. In a study of 177 disease-modifying antirheumatic drug (DMARD)-naive patients with early PsA, they found that those with dactylitis (46%) had significantly higher tender and swollen joint counts and C-reactive protein than those with non-dactylitic PsA. Ultrasound synovitis and erosions were also significantly more prevalent in dactylitic PsA. Thus, the presence of dactylitis indicates a more severe phenotype, and patients with dactylitis should be treated aggressively to improve long-term outcomes.

Novel therapies are being frequently evaluated in PsA and a recent target is interleukin (IL)-23, a key cytokine in the T-helper 17 (Th17) pathway and in the pathogenesis of psoriatic disease. Risankizumab is a novel monoclonal antibody targeting IL-23. In the double-blind phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to one or more conventional synthetic (cs) DMARDs. They were randomly assigned to receive 150 mg risankizumab or placebo, Kristensen et al³ demonstrated that, at week 24, at least a 20% improvement in the American College of Rheumatology score (ACR20) was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent adverse events were mild-to-moderate and reported at similar frequencies in the risankizumab (40.4%) and placebo (38.7%) groups. Thus, risankizumab was efficacious in reducing clinical manifestations of PsA in patients with inadequate response to csDMARDs with no new adverse events. An important question when treating patients with PsA with targeted therapies is the need for concomitant therapy with csDMARDs. In a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2,  1,916 patients with active PsA with an inadequate response to ≥1 non-biologic (nb) DMARDs or biologic DMARDs were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks, Nash et al⁴ demonstrated that at week 12, ACR20 response was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI 24.4%-43.1%; 30 mg: 45.7%; 95% CI 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI 27.9%-40.1%; 30 mg: 39.6%; 95% CI 33.7%-45.5%). Adverse events were generally similar between monotherapy and combination therapy. Although, we don’t have information regarding the sustainability of the response, these data indicate that upadacitinib may be used without concomitant csDMARDs in PsA.

References

1. Karmacharya P et al. Time to transition from psoriasis to psoriatic arthritis: A population-based study. Semin Arthritis Rheum. 2021(Dec 31):S0049-0172(21)00230-4.
2. Dubash S et al. Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis. Ann Rheum Dis. 2021(Dec 10):annrheumdis-2021-220964.
3. Kristensen LE et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022(Feb);81(2):225-231.
4. Nash P et al. Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis. Rheumatology (Oxford). 2021(Dec 3):keab905.

Identifying risk factors associated with transition from cutaneous psoriasis to arthritic psoriasis remains a hot area of research. In a retrospective nested case-control study using the resources of the Rochester Epidemiology Project, Karmacharya et al¹ identified 164 patients with incident PsA between 2000 and 2017. Among the 158 total patients satisfying study criteria, 64 (41%) had concurrent psoriasis and PsA and 94 (59%) had onset of psoriasis before PsA. The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA. Early onset as well as severe psoriasis is associated with the HLA- C*06 allele as is longer psoriasis-PsA latency. Although not evaluated in this study, this genetic factor, or other factors such as detection bias, may underly these observations.

Once diagnosed, stratification of PsA severity is important for planning treatment. Towards this goal, Dubash et al² demonstrated that the presence of dactylitis indicates a more severe PsA phenotype. In a study of 177 disease-modifying antirheumatic drug (DMARD)-naive patients with early PsA, they found that those with dactylitis (46%) had significantly higher tender and swollen joint counts and C-reactive protein than those with non-dactylitic PsA. Ultrasound synovitis and erosions were also significantly more prevalent in dactylitic PsA. Thus, the presence of dactylitis indicates a more severe phenotype, and patients with dactylitis should be treated aggressively to improve long-term outcomes.

Novel therapies are being frequently evaluated in PsA and a recent target is interleukin (IL)-23, a key cytokine in the T-helper 17 (Th17) pathway and in the pathogenesis of psoriatic disease. Risankizumab is a novel monoclonal antibody targeting IL-23. In the double-blind phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to one or more conventional synthetic (cs) DMARDs. They were randomly assigned to receive 150 mg risankizumab or placebo, Kristensen et al³ demonstrated that, at week 24, at least a 20% improvement in the American College of Rheumatology score (ACR20) was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent adverse events were mild-to-moderate and reported at similar frequencies in the risankizumab (40.4%) and placebo (38.7%) groups. Thus, risankizumab was efficacious in reducing clinical manifestations of PsA in patients with inadequate response to csDMARDs with no new adverse events. An important question when treating patients with PsA with targeted therapies is the need for concomitant therapy with csDMARDs. In a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2,  1,916 patients with active PsA with an inadequate response to ≥1 non-biologic (nb) DMARDs or biologic DMARDs were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks, Nash et al⁴ demonstrated that at week 12, ACR20 response was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI 24.4%-43.1%; 30 mg: 45.7%; 95% CI 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI 27.9%-40.1%; 30 mg: 39.6%; 95% CI 33.7%-45.5%). Adverse events were generally similar between monotherapy and combination therapy. Although, we don’t have information regarding the sustainability of the response, these data indicate that upadacitinib may be used without concomitant csDMARDs in PsA.

References

1. Karmacharya P et al. Time to transition from psoriasis to psoriatic arthritis: A population-based study. Semin Arthritis Rheum. 2021(Dec 31):S0049-0172(21)00230-4.
2. Dubash S et al. Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis. Ann Rheum Dis. 2021(Dec 10):annrheumdis-2021-220964.
3. Kristensen LE et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022(Feb);81(2):225-231.
4. Nash P et al. Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis. Rheumatology (Oxford). 2021(Dec 3):keab905.

Identifying risk factors associated with transition from cutaneous psoriasis to arthritic psoriasis remains a hot area of research. In a retrospective nested case-control study using the resources of the Rochester Epidemiology Project, Karmacharya et al¹ identified 164 patients with incident PsA between 2000 and 2017. Among the 158 total patients satisfying study criteria, 64 (41%) had concurrent psoriasis and PsA and 94 (59%) had onset of psoriasis before PsA. The median time from psoriasis diagnosis to the incidence of PsA was 35.5 months with age at psoriasis onset (odds ratio [OR] per 10-year decrease 1.63; 95% CI 1.26-2.11) and its severity (OR for severe vs. mild 3.65; 95% CI 1.18-11.32) being associated with having a psoriasis diagnosis >1 year prior to incident PsA. Early onset as well as severe psoriasis is associated with the HLA- C*06 allele as is longer psoriasis-PsA latency. Although not evaluated in this study, this genetic factor, or other factors such as detection bias, may underly these observations.

Once diagnosed, stratification of PsA severity is important for planning treatment. Towards this goal, Dubash et al² demonstrated that the presence of dactylitis indicates a more severe PsA phenotype. In a study of 177 disease-modifying antirheumatic drug (DMARD)-naive patients with early PsA, they found that those with dactylitis (46%) had significantly higher tender and swollen joint counts and C-reactive protein than those with non-dactylitic PsA. Ultrasound synovitis and erosions were also significantly more prevalent in dactylitic PsA. Thus, the presence of dactylitis indicates a more severe phenotype, and patients with dactylitis should be treated aggressively to improve long-term outcomes.

Novel therapies are being frequently evaluated in PsA and a recent target is interleukin (IL)-23, a key cytokine in the T-helper 17 (Th17) pathway and in the pathogenesis of psoriatic disease. Risankizumab is a novel monoclonal antibody targeting IL-23. In the double-blind phase 3 KEEPsAKE 1 study including 964 patients with active PsA and inadequate response to one or more conventional synthetic (cs) DMARDs. They were randomly assigned to receive 150 mg risankizumab or placebo, Kristensen et al³ demonstrated that, at week 24, at least a 20% improvement in the American College of Rheumatology score (ACR20) was achieved by a significantly higher proportion of patients receiving risankizumab vs. placebo (57.3% vs. 33.5%; P < .001). Treatment-emergent adverse events were mild-to-moderate and reported at similar frequencies in the risankizumab (40.4%) and placebo (38.7%) groups. Thus, risankizumab was efficacious in reducing clinical manifestations of PsA in patients with inadequate response to csDMARDs with no new adverse events. An important question when treating patients with PsA with targeted therapies is the need for concomitant therapy with csDMARDs. In a pooled analysis of 2 phase 3 trials, SELECT-PsA 1 and SELECT-PsA 2,  1,916 patients with active PsA with an inadequate response to ≥1 non-biologic (nb) DMARDs or biologic DMARDs were randomly assigned to placebo, 15 mg upadacitinib, or 30 mg upadacitinib as monotherapy or in combination with ≤2 nbDMARDs for 24 weeks, Nash et al⁴ demonstrated that at week 12, ACR20 response was achieved by a similar proportion of patients receiving 15 mg upadacitinib or 30 mg upadacitinib as monotherapy (15 mg: 33.7%; 95% CI 24.4%-43.1%; 30 mg: 45.7%; 95% CI 36.9%-54.5%) or combination therapy (15 mg: 34.0%; 95% CI 27.9%-40.1%; 30 mg: 39.6%; 95% CI 33.7%-45.5%). Adverse events were generally similar between monotherapy and combination therapy. Although, we don’t have information regarding the sustainability of the response, these data indicate that upadacitinib may be used without concomitant csDMARDs in PsA.

References

1. Karmacharya P et al. Time to transition from psoriasis to psoriatic arthritis: A population-based study. Semin Arthritis Rheum. 2021(Dec 31):S0049-0172(21)00230-4.
2. Dubash S et al. Dactylitis is an indicator of a more severe phenotype independently associated with greater SJC, CRP, ultrasound synovitis and erosive damage in DMARD-naive early psoriatic arthritis. Ann Rheum Dis. 2021(Dec 10):annrheumdis-2021-220964.
3. Kristensen LE et al. Efficacy and safety of risankizumab for active psoriatic arthritis: 24-week results from the randomised, double-blind, phase 3 KEEPsAKE 1 trial. Ann Rheum Dis. 2022(Feb);81(2):225-231.
4. Nash P et al. Upadacitinib as monotherapy and in combination with non-biologic disease-modifying antirheumatic drugs for psoriatic arthritis. Rheumatology (Oxford). 2021(Dec 3):keab905.

After participating in the activity, PCPs should be able to:

• Assess a patient with possible signs and symptoms of opioid use disorder
• Identify criteria necessary to make a diagnosis of opioid use disorder
• Recognize factors that should be considered to tailor treatments for patients with opioid use disorder
• Select the best treatment option for patients with opioid use disorder

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After participating in the activity, PCPs should be able to:

• Assess a patient with possible signs and symptoms of opioid use disorder
• Identify criteria necessary to make a diagnosis of opioid use disorder
• Recognize factors that should be considered to tailor treatments for patients with opioid use disorder
• Select the best treatment option for patients with opioid use disorder

Click here to access this content now 

After participating in the activity, PCPs should be able to:

• Assess a patient with possible signs and symptoms of opioid use disorder
• Identify criteria necessary to make a diagnosis of opioid use disorder
• Recognize factors that should be considered to tailor treatments for patients with opioid use disorder
• Select the best treatment option for patients with opioid use disorder

Click here to access this content now 

Breast cancer diagnosis and treatment in young women can present unique challenges based on their life stage, including potential impact on fertility and future pregnancy. The role of GnRH analogues for ovarian protection during chemotherapy has been shown in both the POEMS-SWOG S0230 and PROMISE-GIM6 studies. Zong and colleagues conducted a phase 3 trial in China among premenopausal women with stage I-III breast cancer receiving cyclophosphamide-containing chemotherapy, with randomization to GnRHa + chemotherapy vs chemotherapy alone. Among 301 patients eligible for primary endpoint analysis, the premature ovarian insufficiency rate at 12 months was 10.3% for the GnRHa group vs 44.5% for the control group (odds ratio 0.23; P < 0.001). The rate of ovarian function recovery was also 46.4% higher in the GnRHa group. Furthermore, although survival outcomes were similar between groups, in patients <35 years of age, the tumor-free survival was higher in the GnRHa group vs control (93% vs 62%, P = 0.004) (Zong et al). These data reinforce the role of GnRHa as a means to reduce POI risk and support ovarian function recovery in young women undergoing chemotherapy for breast cancer. Measures of fertility and timing of pregnancy after breast cancer diagnosis continue to be areas of active research.

The treatment landscape for early-stage HER2-positive breast cancer continues to rapidly evolve with efforts to enhance efficacy and minimize toxicity for patients. The phase 3 KAITLIN study included 1846 patients with early-stage HER2-positive breast cancer (node-positive or node-negative, hormone receptor-negative and ≥T2 primary tumor) with randomization after surgery to adjuvant AC followed by taxane + trastuzumab + pertuzumab (AC-THP) or AC followed by T-DM1 + pertuzumab (AC-KP). In both the overall and node-positive populations, there was no significant difference in IDFS between the arms (stratified HR 0.98 and 0.97, respectively). In the overall population, the 3-year IDFS was 93.1% for AC-KP and 94.2% for AC-THP. Treatment completion rates were lower for AC-KP vs AC-THP (65.0% vs 88.4%), with T-DM1 discontinuation driven mostly by lab abnormalities (elevated liver function tests and thrombocytopenia) (Krop et al). Many patients diagnosed with early HER2-positive breast cancer (specifically those with tumors >2cm or node-positive) are treated with neoadjuvant chemotherapy + HER2-targeted therapy with subsequent tailoring of adjuvant treatment pending response, including use of T-DM1 if residual disease present. Future escalation and de-escalation strategies are being explored to further optimize outcomes and decrease side effects.

The addition of CDK 4/6 inhibitors to endocrine therapy has led to improved survival outcomes for patients diagnosed with advanced HR-positive-HER2-negative breast cancer. Lu and colleagues presented exploratory updated OS results among 672 patients with extended follow-up (median 53.5 months) from MONALEESA-7, which was a phase 3 randomized trial of ribociclib + endocrine therapy vs endocrine therapy alone among peri/pre-menopausal patients with HR-positive/HER2-negative advanced breast cancer. Median OS was 58.7 months vs 48.0 months for the ribociclib and placebo arms, respectively (HR 0.76), and a more pronounced benefit was seen in patients <40 years of age (median OS 51.3 months vs 40.5 months for ribociclib vs placebo arm; HR 0.65) (Lu et al). Furthermore, there was a significant delay in time to chemotherapy with ribociclib vs placebo (50.9 months vs 36.8 months; HR 0.69) which can certainly impact quality of life. A prior pooled analysis of the various MONALEESA trials demonstrated consistent PFS benefit with ribociclib across all intrinsic breast cancer subtypes, with the exception of basal-like and a more pronounced favorable impact in HER2-enriched. Future research to elucidate differences among CDK 4/6 inhibitors, influence of breast cancer subtype on their effect and how this can be translated to routine clinical practice are warranted.

Breast cancer diagnosis and treatment in young women can present unique challenges based on their life stage, including potential impact on fertility and future pregnancy. The role of GnRH analogues for ovarian protection during chemotherapy has been shown in both the POEMS-SWOG S0230 and PROMISE-GIM6 studies. Zong and colleagues conducted a phase 3 trial in China among premenopausal women with stage I-III breast cancer receiving cyclophosphamide-containing chemotherapy, with randomization to GnRHa + chemotherapy vs chemotherapy alone. Among 301 patients eligible for primary endpoint analysis, the premature ovarian insufficiency rate at 12 months was 10.3% for the GnRHa group vs 44.5% for the control group (odds ratio 0.23; P < 0.001). The rate of ovarian function recovery was also 46.4% higher in the GnRHa group. Furthermore, although survival outcomes were similar between groups, in patients <35 years of age, the tumor-free survival was higher in the GnRHa group vs control (93% vs 62%, P = 0.004) (Zong et al). These data reinforce the role of GnRHa as a means to reduce POI risk and support ovarian function recovery in young women undergoing chemotherapy for breast cancer. Measures of fertility and timing of pregnancy after breast cancer diagnosis continue to be areas of active research.

The treatment landscape for early-stage HER2-positive breast cancer continues to rapidly evolve with efforts to enhance efficacy and minimize toxicity for patients. The phase 3 KAITLIN study included 1846 patients with early-stage HER2-positive breast cancer (node-positive or node-negative, hormone receptor-negative and ≥T2 primary tumor) with randomization after surgery to adjuvant AC followed by taxane + trastuzumab + pertuzumab (AC-THP) or AC followed by T-DM1 + pertuzumab (AC-KP). In both the overall and node-positive populations, there was no significant difference in IDFS between the arms (stratified HR 0.98 and 0.97, respectively). In the overall population, the 3-year IDFS was 93.1% for AC-KP and 94.2% for AC-THP. Treatment completion rates were lower for AC-KP vs AC-THP (65.0% vs 88.4%), with T-DM1 discontinuation driven mostly by lab abnormalities (elevated liver function tests and thrombocytopenia) (Krop et al). Many patients diagnosed with early HER2-positive breast cancer (specifically those with tumors >2cm or node-positive) are treated with neoadjuvant chemotherapy + HER2-targeted therapy with subsequent tailoring of adjuvant treatment pending response, including use of T-DM1 if residual disease present. Future escalation and de-escalation strategies are being explored to further optimize outcomes and decrease side effects.

The addition of CDK 4/6 inhibitors to endocrine therapy has led to improved survival outcomes for patients diagnosed with advanced HR-positive-HER2-negative breast cancer. Lu and colleagues presented exploratory updated OS results among 672 patients with extended follow-up (median 53.5 months) from MONALEESA-7, which was a phase 3 randomized trial of ribociclib + endocrine therapy vs endocrine therapy alone among peri/pre-menopausal patients with HR-positive/HER2-negative advanced breast cancer. Median OS was 58.7 months vs 48.0 months for the ribociclib and placebo arms, respectively (HR 0.76), and a more pronounced benefit was seen in patients <40 years of age (median OS 51.3 months vs 40.5 months for ribociclib vs placebo arm; HR 0.65) (Lu et al). Furthermore, there was a significant delay in time to chemotherapy with ribociclib vs placebo (50.9 months vs 36.8 months; HR 0.69) which can certainly impact quality of life. A prior pooled analysis of the various MONALEESA trials demonstrated consistent PFS benefit with ribociclib across all intrinsic breast cancer subtypes, with the exception of basal-like and a more pronounced favorable impact in HER2-enriched. Future research to elucidate differences among CDK 4/6 inhibitors, influence of breast cancer subtype on their effect and how this can be translated to routine clinical practice are warranted.

Breast cancer diagnosis and treatment in young women can present unique challenges based on their life stage, including potential impact on fertility and future pregnancy. The role of GnRH analogues for ovarian protection during chemotherapy has been shown in both the POEMS-SWOG S0230 and PROMISE-GIM6 studies. Zong and colleagues conducted a phase 3 trial in China among premenopausal women with stage I-III breast cancer receiving cyclophosphamide-containing chemotherapy, with randomization to GnRHa + chemotherapy vs chemotherapy alone. Among 301 patients eligible for primary endpoint analysis, the premature ovarian insufficiency rate at 12 months was 10.3% for the GnRHa group vs 44.5% for the control group (odds ratio 0.23; P < 0.001). The rate of ovarian function recovery was also 46.4% higher in the GnRHa group. Furthermore, although survival outcomes were similar between groups, in patients <35 years of age, the tumor-free survival was higher in the GnRHa group vs control (93% vs 62%, P = 0.004) (Zong et al). These data reinforce the role of GnRHa as a means to reduce POI risk and support ovarian function recovery in young women undergoing chemotherapy for breast cancer. Measures of fertility and timing of pregnancy after breast cancer diagnosis continue to be areas of active research.

The treatment landscape for early-stage HER2-positive breast cancer continues to rapidly evolve with efforts to enhance efficacy and minimize toxicity for patients. The phase 3 KAITLIN study included 1846 patients with early-stage HER2-positive breast cancer (node-positive or node-negative, hormone receptor-negative and ≥T2 primary tumor) with randomization after surgery to adjuvant AC followed by taxane + trastuzumab + pertuzumab (AC-THP) or AC followed by T-DM1 + pertuzumab (AC-KP). In both the overall and node-positive populations, there was no significant difference in IDFS between the arms (stratified HR 0.98 and 0.97, respectively). In the overall population, the 3-year IDFS was 93.1% for AC-KP and 94.2% for AC-THP. Treatment completion rates were lower for AC-KP vs AC-THP (65.0% vs 88.4%), with T-DM1 discontinuation driven mostly by lab abnormalities (elevated liver function tests and thrombocytopenia) (Krop et al). Many patients diagnosed with early HER2-positive breast cancer (specifically those with tumors >2cm or node-positive) are treated with neoadjuvant chemotherapy + HER2-targeted therapy with subsequent tailoring of adjuvant treatment pending response, including use of T-DM1 if residual disease present. Future escalation and de-escalation strategies are being explored to further optimize outcomes and decrease side effects.

The addition of CDK 4/6 inhibitors to endocrine therapy has led to improved survival outcomes for patients diagnosed with advanced HR-positive-HER2-negative breast cancer. Lu and colleagues presented exploratory updated OS results among 672 patients with extended follow-up (median 53.5 months) from MONALEESA-7, which was a phase 3 randomized trial of ribociclib + endocrine therapy vs endocrine therapy alone among peri/pre-menopausal patients with HR-positive/HER2-negative advanced breast cancer. Median OS was 58.7 months vs 48.0 months for the ribociclib and placebo arms, respectively (HR 0.76), and a more pronounced benefit was seen in patients <40 years of age (median OS 51.3 months vs 40.5 months for ribociclib vs placebo arm; HR 0.65) (Lu et al). Furthermore, there was a significant delay in time to chemotherapy with ribociclib vs placebo (50.9 months vs 36.8 months; HR 0.69) which can certainly impact quality of life. A prior pooled analysis of the various MONALEESA trials demonstrated consistent PFS benefit with ribociclib across all intrinsic breast cancer subtypes, with the exception of basal-like and a more pronounced favorable impact in HER2-enriched. Future research to elucidate differences among CDK 4/6 inhibitors, influence of breast cancer subtype on their effect and how this can be translated to routine clinical practice are warranted.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: Upadacitinib alone or in combination with methotrexate inhibits structural joint damage progression over a year in patients with rheumatoid arthritis (RA).

Major finding: The mean change in modified total Sharp score (mTSS) at 1 year for 15 mg upadacitinib and 30 mg upadacitinib vs. methotrexate was 0.03 and 0.14 vs. 1.00 (all P < .001). In methotrexate-inadequate responders (IR), mean change in mTSS with 15 mg upadacitinib vs. placebo (both with background methotrexate) was 0.28 vs. 1.73 (P < .001).

Study details: This was an analysis of 2 phase 3 trials involving patients with active RA who were either methotrexate-naive (SELECT-EARLY) and were randomly assigned to methotrexate monotherapy, 15 mg upadacitinib, or 30 mg upadacitinib or were methotrexate-IR (SELECT-COMPARE) and were randomly assigned to either 15 mg upadacitinib, 40 mg adalimumab, or placebo, all with background methotrexate.

Disclosures: This study was funded by AbbVie. IH Song, A Friedman, T Shaw, Y Li, S Chen, and JV Enejosa reported being full-time employees or owning stocks/stock options of AbbVie, and others reported receiving research grants and consultancy or speakers fees from various sources including AbbVie.

Source: Peterfy CG et al. Rheumatology (Oxford). 2021;keab861 (Dec 13). Doi:  10.1093/rheumatology/keab861.

Key clinical point: A clinically noteworthy improvement in mental health was observed in patients with rheumatoid arthritis (RA) who were treated with Janus kinase (JAK) inhibitors.

Major finding: The pooled incremental mean reduction in short form-36 mental component score with JAK monotherapy was 4.95 (95% CI 4.41-5.48), which was greater than the minimum clinically important difference value of 2.5, indicating significant improvement in mental health following JAK monotherapy.

Study details: This was a meta-analysis of 19 studies involving 14,323 patients with RA.

Disclosures: This study received no specific funding. The authors did not have any potential conflict of interests.

Source: Shamail GMH et al. Rheumatol Ther. 2021 (Dec 13). Doi: 10.1007/s40744-021-00409-6.

Key clinical point: A clinically noteworthy improvement in mental health was observed in patients with rheumatoid arthritis (RA) who were treated with Janus kinase (JAK) inhibitors.

Major finding: The pooled incremental mean reduction in short form-36 mental component score with JAK monotherapy was 4.95 (95% CI 4.41-5.48), which was greater than the minimum clinically important difference value of 2.5, indicating significant improvement in mental health following JAK monotherapy.

Study details: This was a meta-analysis of 19 studies involving 14,323 patients with RA.

Disclosures: This study received no specific funding. The authors did not have any potential conflict of interests.

Source: Shamail GMH et al. Rheumatol Ther. 2021 (Dec 13). Doi: 10.1007/s40744-021-00409-6.

Key clinical point: A clinically noteworthy improvement in mental health was observed in patients with rheumatoid arthritis (RA) who were treated with Janus kinase (JAK) inhibitors.

Major finding: The pooled incremental mean reduction in short form-36 mental component score with JAK monotherapy was 4.95 (95% CI 4.41-5.48), which was greater than the minimum clinically important difference value of 2.5, indicating significant improvement in mental health following JAK monotherapy.

Study details: This was a meta-analysis of 19 studies involving 14,323 patients with RA.

Disclosures: This study received no specific funding. The authors did not have any potential conflict of interests.

Source: Shamail GMH et al. Rheumatol Ther. 2021 (Dec 13). Doi: 10.1007/s40744-021-00409-6.

Key clinical point: In a cohort of patients with early rheumatoid arthritis (RA), illness perceptions and suboptimal psychosocial well-being were associated with a lower likelihood of sustained remission.

Major finding: Among patients who were had a disease activity score in 28 joints-C-reactive protein remission at week 16, those with a low vs. high psychosocial burden profile showed a significantly longer time to first loss-of-remission (hazard ratio 0.51; P < .001).

Study details: This was a post hoc analysis of the CareRA trial involving 379 patients with early RA who received methotrexate ± additional conventional synthetic disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This study was supported in part by a Strategic Basic Research Fellowship grant from Fonds Wetenschappelijk Onderzoek. All the authors declared no conflicts of interest.

Source: Doumen M et al. Arthritis Care Res (Hoboken). 2021 (Dec 20). Doi: 10.1002/acr.24847.

Key clinical point: In a cohort of patients with early rheumatoid arthritis (RA), illness perceptions and suboptimal psychosocial well-being were associated with a lower likelihood of sustained remission.

Major finding: Among patients who were had a disease activity score in 28 joints-C-reactive protein remission at week 16, those with a low vs. high psychosocial burden profile showed a significantly longer time to first loss-of-remission (hazard ratio 0.51; P < .001).

Study details: This was a post hoc analysis of the CareRA trial involving 379 patients with early RA who received methotrexate ± additional conventional synthetic disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This study was supported in part by a Strategic Basic Research Fellowship grant from Fonds Wetenschappelijk Onderzoek. All the authors declared no conflicts of interest.

Source: Doumen M et al. Arthritis Care Res (Hoboken). 2021 (Dec 20). Doi: 10.1002/acr.24847.

Key clinical point: In a cohort of patients with early rheumatoid arthritis (RA), illness perceptions and suboptimal psychosocial well-being were associated with a lower likelihood of sustained remission.

Major finding: Among patients who were had a disease activity score in 28 joints-C-reactive protein remission at week 16, those with a low vs. high psychosocial burden profile showed a significantly longer time to first loss-of-remission (hazard ratio 0.51; P < .001).

Study details: This was a post hoc analysis of the CareRA trial involving 379 patients with early RA who received methotrexate ± additional conventional synthetic disease-modifying antirheumatic drugs or glucocorticoids.

Disclosures: This study was supported in part by a Strategic Basic Research Fellowship grant from Fonds Wetenschappelijk Onderzoek. All the authors declared no conflicts of interest.

Source: Doumen M et al. Arthritis Care Res (Hoboken). 2021 (Dec 20). Doi: 10.1002/acr.24847.

Key clinical point: Celecoxib appeared to be relatively safer compared with nonselective nonsteroidal anti-inflammatory drugs (NSAID) or placebo in patients with rheumatoid arthritis (RA), regardless of dose or duration.

Major finding: Celecoxib was associated with a lower risk for all-cause mortality (risk ratio [RR] 0.81; 95% CI 0.66-0.98) and cardiovascular morality (RR 0.75; 95% CI 0.57-0.99) compared with NSAIDs and a similar risk for all-cause mortality (RR 0.92; 95% CI 0.26-3.27) and cardiovascular morality (RR 3.02; 95% CI 0.36-25.27) compared with placebo.

Study details: Findings are from a meta-analysis of 21 randomized clinical studies that compared cardiovascular safety of celecoxib with NSAIDs or placebo in patients with RA or osteoarthritis.

Disclosures: This study was supported by the National Natural Science Foundation project and others. No competing interests were declared.

Source: Cheng BR et al. PLoS One. 2021;16(12):e0261239 (Dec 21). Doi:  10.1371/journal.pone.0261239.

Key clinical point: Celecoxib appeared to be relatively safer compared with nonselective nonsteroidal anti-inflammatory drugs (NSAID) or placebo in patients with rheumatoid arthritis (RA), regardless of dose or duration.

Major finding: Celecoxib was associated with a lower risk for all-cause mortality (risk ratio [RR] 0.81; 95% CI 0.66-0.98) and cardiovascular morality (RR 0.75; 95% CI 0.57-0.99) compared with NSAIDs and a similar risk for all-cause mortality (RR 0.92; 95% CI 0.26-3.27) and cardiovascular morality (RR 3.02; 95% CI 0.36-25.27) compared with placebo.

Study details: Findings are from a meta-analysis of 21 randomized clinical studies that compared cardiovascular safety of celecoxib with NSAIDs or placebo in patients with RA or osteoarthritis.

Disclosures: This study was supported by the National Natural Science Foundation project and others. No competing interests were declared.

Source: Cheng BR et al. PLoS One. 2021;16(12):e0261239 (Dec 21). Doi:  10.1371/journal.pone.0261239.

Key clinical point: Celecoxib appeared to be relatively safer compared with nonselective nonsteroidal anti-inflammatory drugs (NSAID) or placebo in patients with rheumatoid arthritis (RA), regardless of dose or duration.

Major finding: Celecoxib was associated with a lower risk for all-cause mortality (risk ratio [RR] 0.81; 95% CI 0.66-0.98) and cardiovascular morality (RR 0.75; 95% CI 0.57-0.99) compared with NSAIDs and a similar risk for all-cause mortality (RR 0.92; 95% CI 0.26-3.27) and cardiovascular morality (RR 3.02; 95% CI 0.36-25.27) compared with placebo.

Study details: Findings are from a meta-analysis of 21 randomized clinical studies that compared cardiovascular safety of celecoxib with NSAIDs or placebo in patients with RA or osteoarthritis.

Disclosures: This study was supported by the National Natural Science Foundation project and others. No competing interests were declared.

Source: Cheng BR et al. PLoS One. 2021;16(12):e0261239 (Dec 21). Doi:  10.1371/journal.pone.0261239.

Key clinical point: Patients with rheumatoid arthritis (RA) experienced robust pain reduction with baricitinib, irrespective of opioid use.

Major finding: Compared with placebo, pain reduction was significantly greater at all time points, starting as early as week 1 (all P < .05) in both opioid users and nonusers receiving 4 mg baricitinib and only in opioid users receiving 2 mg baricitinib. Opioid nonusers receiving 2 mg baricitinib showed greater pain relief than placebo starting at week 4 (P < .05).

Study details: This was a post hoc analysis of 3 randomized controlled trials (RA-BEAM, RA-BUILD, and RA-BEACON) involving patients with RA with an inadequate response to either methotrexate, conventional disease-modifying antirheumatic drugs, or at least 1 tumor necrosis factor inhibitor, who were randomly assigned to either placebo, baricitinib (2 mg/4 mg), or adalimumab (40 mg) in addition to background therapy.

Disclosures: This study was funded by Eli Lilly under license from Incyte Corporation. The authors declared no conflict of interests.

Source: Pope JE et al. ACR Open Rheumatol. 2021 (Dec 16). Doi: 10.1002/acr2.11380.

Key clinical point: Patients with rheumatoid arthritis (RA) experienced robust pain reduction with baricitinib, irrespective of opioid use.

Major finding: Compared with placebo, pain reduction was significantly greater at all time points, starting as early as week 1 (all P < .05) in both opioid users and nonusers receiving 4 mg baricitinib and only in opioid users receiving 2 mg baricitinib. Opioid nonusers receiving 2 mg baricitinib showed greater pain relief than placebo starting at week 4 (P < .05).

Study details: This was a post hoc analysis of 3 randomized controlled trials (RA-BEAM, RA-BUILD, and RA-BEACON) involving patients with RA with an inadequate response to either methotrexate, conventional disease-modifying antirheumatic drugs, or at least 1 tumor necrosis factor inhibitor, who were randomly assigned to either placebo, baricitinib (2 mg/4 mg), or adalimumab (40 mg) in addition to background therapy.

Disclosures: This study was funded by Eli Lilly under license from Incyte Corporation. The authors declared no conflict of interests.

Source: Pope JE et al. ACR Open Rheumatol. 2021 (Dec 16). Doi: 10.1002/acr2.11380.

Key clinical point: Patients with rheumatoid arthritis (RA) experienced robust pain reduction with baricitinib, irrespective of opioid use.

Major finding: Compared with placebo, pain reduction was significantly greater at all time points, starting as early as week 1 (all P < .05) in both opioid users and nonusers receiving 4 mg baricitinib and only in opioid users receiving 2 mg baricitinib. Opioid nonusers receiving 2 mg baricitinib showed greater pain relief than placebo starting at week 4 (P < .05).

Study details: This was a post hoc analysis of 3 randomized controlled trials (RA-BEAM, RA-BUILD, and RA-BEACON) involving patients with RA with an inadequate response to either methotrexate, conventional disease-modifying antirheumatic drugs, or at least 1 tumor necrosis factor inhibitor, who were randomly assigned to either placebo, baricitinib (2 mg/4 mg), or adalimumab (40 mg) in addition to background therapy.

Disclosures: This study was funded by Eli Lilly under license from Incyte Corporation. The authors declared no conflict of interests.

Source: Pope JE et al. ACR Open Rheumatol. 2021 (Dec 16). Doi: 10.1002/acr2.11380.

Key clinical point: Significant improvement in patient-reported outcomes was observed with filgotinib in patients with rheumatoid arthritis (RA) with an insufficient response to methotrexate or biological disease-modifying antirheumatic drugs (DMARD) and those who were methotrexate-naive.

Major finding: Filgotinib at doses of 200 mg or 100 mg in combination with methotrexate/conventional synthetic DMARDs or 200 mg filgotinib monotherapy demonstrated a significant improvement in the health-related quality of life, fatigue, and assessments of disease activity and work impairment vs. comparators (all P < .05).

Study details: This was a post hoc analysis of phase 3 studies including patients with RA with an inadequate response to methotrexate (FINCH 1) or biological DMARDs (FINCH 2) and those who were methotrexate-naive (FINCH 3).

Disclosures: This study was supported by Gilead Sciences, Inc., Foster City, CA. SJ Lee, L Ye, and H Hu reported being employees and shareholders of Gilead Sciences. All the other authors disclosed receiving grants/research support and speaker/consultancy fees from various companies including Gilead Sciences.

Source: Bingham CO III et al. Arthritis Res Ther. 2022;24:11 (Jan 3). Doi: 10.1186/s13075-021-02677-7.

Key clinical point: Significant improvement in patient-reported outcomes was observed with filgotinib in patients with rheumatoid arthritis (RA) with an insufficient response to methotrexate or biological disease-modifying antirheumatic drugs (DMARD) and those who were methotrexate-naive.

Major finding: Filgotinib at doses of 200 mg or 100 mg in combination with methotrexate/conventional synthetic DMARDs or 200 mg filgotinib monotherapy demonstrated a significant improvement in the health-related quality of life, fatigue, and assessments of disease activity and work impairment vs. comparators (all P < .05).

Study details: This was a post hoc analysis of phase 3 studies including patients with RA with an inadequate response to methotrexate (FINCH 1) or biological DMARDs (FINCH 2) and those who were methotrexate-naive (FINCH 3).

Disclosures: This study was supported by Gilead Sciences, Inc., Foster City, CA. SJ Lee, L Ye, and H Hu reported being employees and shareholders of Gilead Sciences. All the other authors disclosed receiving grants/research support and speaker/consultancy fees from various companies including Gilead Sciences.

Source: Bingham CO III et al. Arthritis Res Ther. 2022;24:11 (Jan 3). Doi: 10.1186/s13075-021-02677-7.

Key clinical point: Significant improvement in patient-reported outcomes was observed with filgotinib in patients with rheumatoid arthritis (RA) with an insufficient response to methotrexate or biological disease-modifying antirheumatic drugs (DMARD) and those who were methotrexate-naive.

Major finding: Filgotinib at doses of 200 mg or 100 mg in combination with methotrexate/conventional synthetic DMARDs or 200 mg filgotinib monotherapy demonstrated a significant improvement in the health-related quality of life, fatigue, and assessments of disease activity and work impairment vs. comparators (all P < .05).

Study details: This was a post hoc analysis of phase 3 studies including patients with RA with an inadequate response to methotrexate (FINCH 1) or biological DMARDs (FINCH 2) and those who were methotrexate-naive (FINCH 3).

Disclosures: This study was supported by Gilead Sciences, Inc., Foster City, CA. SJ Lee, L Ye, and H Hu reported being employees and shareholders of Gilead Sciences. All the other authors disclosed receiving grants/research support and speaker/consultancy fees from various companies including Gilead Sciences.

Source: Bingham CO III et al. Arthritis Res Ther. 2022;24:11 (Jan 3). Doi: 10.1186/s13075-021-02677-7.