Clinical Data in Rheumatoid Arthritis

Use the links below to browse through clinical experience with Acthar.

Acthar is an adrenocorticotropic hormone (ACTH) analogue used for adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy).

Fleischmann (2018): Acthar in Patients With Persistently Active Rheumatoid Arthritis Previously Treated With 1 to 2 DMARDs and Corticosteroids

Gillis (2017): Acthar as Adjunctive Therapy in Patients With Rheumatoid Arthritis Who Have Failed Previous Therapies With at Least Three Different Modes of Action

Brown (2015): Acthar in Patients With Refractory Rheumatoid Arthritis: A Case Series

Fleischmann (2018): Acthar in Patients With Persistently Active Rheumatoid Arthritis Previously Treated With 1 to 2 DMARDs and Corticosteroids

Study Design

Acthar was assessed in an open-label phase of an ongoing study of 116 patients. This interim report summarizes data collected through May 10, 2018.1 Funding to support the preparation of this content was provided by Mallinckrodt Pharmaceuticals.

Background

  • Disease-modifying anti-rheumatic drugs (DMARDs) are standard of care for patients with RA
  • Corticosteroids are recommended as adjunct therapy during DMARD initiation or during a change in DMARDs2

Methods

Enlarge the adjacent chart to see the way the study is structured.

  • Part 1: 12-week open-label treatment phase – Participating patients received Acthar 80 U SC twice a week for the entire 12-week period
  • Part 2: Double-blind randomized phase – Patients who achieved LDA as defined as DAS28-ESR Score ≤3.2 at Week 12 were entered into the second portion of the study, where they received either Acthar 80 U SC twice a week or placebo (1 mL) SC twice a week
    • Patients who did not achieve LDA at Week 12 or who experienced an RA flare were discontinued from the study
    • RA flare is defined as an increase of >0.6 DAS28-ESR from Week 0 sustained over 2 consecutive visits or an increase of >1 DAS28-ESR from Week 0 at a single visit
  • Primary endpoint was the proportion of patients who achieved LDA at Week 12 defined as DAS28-ESR ≤3.2
  • Secondary endpoints measures included DAS28-ESR scores over time; ACR response criteria with improvements of 20%, 50%, or 70%; CDAI change from baseline over time; and Patient-Reported Outcomes (PROs) change from baseline over time

Study Withdrawals

  • As of May 10, 2018, 100 patients out of the 116 patients enrolled in the study had completed the 12-week open-label treatment phase (Part 1)
  • 14 patients had discontinued due to: withdrawal by the patient (n=9); met withdrawal criteria (n=1); other reasons (n=4)
  • 2 patients had not completed Part 1 of the study

ACR=American College of Rheumatology; AEs=adverse events; CDAI=Clinical Disease Activity Index; DAS28-ESR=Disease Activity Score with 28 joint count and Erythrocyte Sedimentation Rate; DMARD=disease-modifying antirheumatic drug; LDA=low disease activity; SC=subcutaneously.

*The proportion of patients who achieved LDA (DAS28-ESR ≤3.2) at Week 12.

Study Limitations

  • Data reported here are from a preplanned 50% data review of the open-label phase of an ongoing study. This is an interim analysis of 116 patients in a larger 2-part study with no comparator arm in Part 1. The trial is now fully enrolled with 232 patients. Because this is an interim report, significance tests were not conducted, and therefore P values are not reported. Full results of this study may vary from the interim analysis1,4
  • Sample bias may exist since this was an open-label phase of an ongoing study, and patients were aware that they were receiving Acthar1
  • Examiner bias may also exist as the patient had to reach low disease activity in order to enter the second phase of the study1
  • The results cannot be solely attributed to Acthar since patients were on different medications at the start of the trial and no washout periods were undertaken. Acthar has not been formally studied in combination with other treatments1

Patient Overview

  • As of May 10, 2018, 100 patients out of the 116 patients enrolled in the study had completed the 12-week open-label treatment phase (Part 1)

Key Inclusion Criteria

Key Inclusion Criteria

Key Exclusion Criteria

Key Exclusion Criteria

Patients Who Completed the 12-week Open-Label Treatment Phase (n=100)

Patients Who Completed the 12-week Open-Label Treatment Phase (n=100)

DMARDs Permitted During the Study

DMARDs Permitted During the Study

EULAR=European League Against Rheumatism.

*Targeted synthetic DMARD (tsDMARD).

Results

  • A decrease in DAS28-ESR scores in patients treated with Acthar was observed over time through Week 12
  • 61% (n=70) of Acthar-treated patients had achieved LDA (DAS28-ESR ≤3.2) at Week 12
  • ACR 20/50/70 response was achieved by 85%, 66%, and 34% of patients, respectively, assessed at Week 12
  • Mean HAQ-DI scores decreased over the study period through Week 12

Interim Results—Primary Endpoint1*

Enlarge the adjacent charts to see the interim results of the primary and secondary endpoints.

Interim Results—Secondary Endpoints1

Mean PRO Scores Improved From Week 4 Through Week 12 During Treatment With Acthar

Mean PRO Scores Improved From Week 4 Through Week 12 During Treatment With Acthar

*Proportion of patients who achieved LDA at Week 12 defined as DAS28-ESR ≤3.2.

This patient represents a protocol deviation.

Values represent the minimally important difference (MID) of 3–4 on a scale of 0–52.

§Values represent the minimum clinically important improvement (MCII).

ND=MCID not determined.

Study Limitations

  • Data reported here are from a preplanned 50% data review of the open-label phase of an ongoing study. This is an interim analysis of 116 patients in a larger 2-part study with no comparator arm in Part 1. The trial is now fully enrolled with 232 patients. Because this is an interim report, significance tests were not conducted, and therefore P values are not reported. Full results of this study may vary from the interim analysis1,4
  • Sample bias may exist since this was an open-label phase of an ongoing study, and patients were aware that they were receiving Acthar1
  • Examiner bias may also exist as the patient had to reach low disease activity in order to enter the second phase of the study1
  • The results cannot be solely attributed to Acthar since patients were on different medications at the start of the trial and no washout periods were undertaken. Acthar has not been formally studied in combination with other treatments1

Safety Results

  • AEs observed were consistent with those in previous Acthar trials, and no new safety signals were reported

Adverse Events* and Study Withdrawals

DMARDs Permitted During the Study
DMARDs Permitted During the Study

SAE=serious adverse event.

*List of adverse events with ≥2 occurrences. Subjects with multiple occurrences for an event are counted only once.

Gillis (2017): Acthar as Adjunctive Therapy in Patients With Rheumatoid Arthritis Who Have Failed Previous Therapies With at Least Three Different Modes of Action

Study Design8

Acthar was evaluated in an open-label, single-group study of 8 patients.8

Background

  • Despite the availability of effective treatment options, some rheumatoid arthritis (RA) patients haven’t achieved adequate disease control
  • Up to 30% of patients can experience glucocorticoid resistance
  • Between 14% and 38% of patients do not respond to first-line biologics

Methods

  • Open-label, interventional, single-group study of 8 patients with RA
  • Adult male or female patients, aged 18-80 years, with confirmed RA based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria were eligible to participate in the study
  • Patients were required to have refractory disease—treated with ≥3 therapeutic agents with a different MOA for more than 3 months and still have active disease, defined as 6 tender and 6 swollen joints
  • Patients received Acthar 80 IU twice weekly via subcutaneous injection over 12 weeks
  • Patients remained on stable doses of prednisone, biologics, and/or disease-modifying antirheumatic drugs (DMARDs), non-steroidal anti-inflammatory drugs (NSAIDs), and analgesics while being treated with Acthar
  • Primary endpoint measures included the Ritchie-Camp Articular (RCA) Index* and 20-item Health Assessment Questionnaire (HAQ) scores prior to treatment and at 2- to 4-week intervals
  • Secondary endpoint measures included acute erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels

*The Ritchie-Camp Articular Index involves a physician’s examination of the person in which 3 assessments are made. A joint count for tenderness on pressure and/or pain on motion for 68 diarthrodial joints is performed. Each joint is graded on a scale of 0 to 3, where 0=none, 1=positive response on questioning, 2=spontaneous response elicited, and 3=withdrawal by patient on examination. Joint swelling for 66 points is assessed and graded on a scale of 0 to 2, where 0=none, 1=detectable synovial thickening with loss of bony contours, and 2=bulging synovial proliferation with cystic characteristics. Joint tenderness/pain and joint swelling scores were derived by summing the 70 scores for each joint. Scores for each joint are summed to get an index score.9

Health Assessment Questionnaire assesses patient outcomes in 4 domains: disability, discomfort and pain, drug side effects, and cost. It includes 8 sections—dressing, arising, eating, walking, hygiene, reach, grip, and common activities.10

Demographics and Treatment History8

Demographic characteristics at baseline

  • 8 patients (7 women and 1 man) aged 46-808:
    • Mean (SD): 64.6 (12.1)
    • Median: 66
  • Disease duration was 9 years to 39 years
    • Mean (SD): 20.9 (11.6)
    • Median: 19.5

Treatment history of each patient prior to Acthar treatment and concomitant medications

Enlarge the below chart to review the summary baseline characteristics of each patient in the case series.

DMARD=disease-modifying antirheumatic drug. SQ=subcutaneous. QD=daily.

PRN=as needed (Latin: pro re nata).

Results8

Clinical characteristics at baseline and at week 12 of Acthar treatment

CRP=C-reactive protein. DAS28=disease activity score-28. ESR=erythrocyte sedimentation rate. HAQ=health assessment questionnaire.

SD=standard deviation. VAS=visual analog scale.

  • When Acthar therapy was stopped, all improvements gained during the study period were lost by week 16

Study limitations

  • This was a small study with only 8 patients and no comparator arm
  • Sample bias may exist since this was an open-label trial and patients and physicians were aware that they were receiving Acthar
  • The results of the study cannot be solely attributable to Acthar since patients were on different medications at the start of the trial and no washout periods or standardization of concomitant medications were undertaken
  • Acthar has not been formally studied in combination with other treatments

Safety Results8

  • According to the investigators, the majority of AEs reported were mild and resolved and/or were unrelated to Acthar

Brown (2015): Acthar in Patients With Refractory Rheumatoid Arthritis: A Case Series

Study Design11

Acthar was evaluated in a retrospective case series of 5 patients with refractory RA.

Background

Despite advancements in RA treatment, patients with refractory disease could benefit from additional treatment options.

Treatment overview

  • Patients with refractory RA (defined as failure to achieve disease remission with a previous treatment) received Acthar based on its proposed mechanism of action after failing several previous therapies
  • Acthar was used to manage active disease or as a bridge therapy to manage symptoms during transition to new treatment
  • The dose of Acthar was individualized based on the disease and medical condition of the patient

Baseline assessments

Enlarge the below chart to review the summary baseline characteristics of each patient in the case series.

Results11

  • Acthar improved inflammatory markers and patient-reported symptoms
  • Patients taking Acthar saw an improvement in RA symptoms, such as less pain, joint swelling, and tenderness
    • 4 patients saw improvement that continued during therapy and 1 patient had temporary improvement

Study limitations

  • Results are based on a retrospective case series of 5 patients and may not be fully representative of outcomes in the overall patient population. All patients were on other therapies. The clinical outcomes may not be solely attributable to Acthar. Acthar has not been formally studied in combination with other treatments

Treatment response and outcomes

*Inflammatory markers continued to decrease so tofacitinib 5 mg once daily was added and the Acthar dose was further reduced and then discontinued.

After this, patient experienced weight gain and elevated blood pressure so Acthar treatment was discontinued and tofacitinib once daily was added.

Change in ESR (Erythrocyte Sedimentation Rate) levels

Change in CRP (C-Reactive Protein) levels

Change in RAPID-3 (Routine Assessment of Patient Index Data with 3 Measures) score

Safety findings

  • 3 patients experienced fluctuations in blood pressure, weight, and/or glucose levels
  • 1 patient discontinued Acthar due to adverse events

*All Case 5 doses were 40 U BIW.

Maintenance dose=40 U BIW.

IMPORTANT SAFETY INFORMATION

SEE More

Contraindications

  • Acthar should never be administered intravenously
  • Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of Acthar
  • Acthar is contraindicated where congenital infections are suspected in infants
  • Acthar is contraindicated in patients with scleroderma, osteoporosis, systemic fungal infections, ocular herpes simplex, recent surgery, history of or the presence of a peptic ulcer, congestive heart failure, uncontrolled hypertension, primary adrenocortical insufficiency, adrenocortical hyperfunction or sensitivity to proteins of porcine origins

INDICATIONS

SEE More

H.P. Acthar® Gel (repository corticotropin injection) is an adrenocorticotropic hormone (ACTH) analogue used for:

  • Treatment during an exacerbation or as maintenance therapy in selected cases of systemic dermatomyositis (polymyositis)
  • Treatment during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus
  • The treatment of symptomatic sarcoidosis
  • Adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy)