Safe and Effective Method of Treating Psoriatic Arthritis with Anti-IL23 Specific Antibody

Abstract

A method of treating psoriatic arthritis in a patient by administering an IL-23 specific antibody, e.g., guselkumab, in a clinically proven safe and clinically proven effective amount and the patient achieves significant ACR20/50/70, PASI70/90/100, MDA, HAQ-DI, SF-36 PCS, MCS, LEI/dactylitis, PASDAS, GRACE, mCPDAI, DAPSA or RAPID3 improvement as measured 16, 24, 32, 40 and 48 weeks after initial treatment.

What is claimed: 
     
         1 . A method of treating psoriatic arthritis in a patient, comprising administering an antibody to IL-23 to the patient in a clinically proven safe and clinically proven effective amount, wherein the antibody comprises a light chain variable region and a heavy chain variable region, said light chain variable region comprising:
 a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:50;   a CDRL2 amino acid sequence of SEQ ID NO:56; and   a CDRL3 amino acid sequence of SEQ ID NO:73,   said heavy chain variable region comprising:   a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:5;   a CDRH2 amino acid sequence of SEQ ID NO:20; and   a CDRH3 amino acid sequence of SEQ ID NO:44.   
     
     
         2 . The method of  claim 1 , wherein the antibody is administered in an initial subcutaneous dose at week 0, a subcutaneous dose at week 4 and a subcutaneous dose every 8 weeks thereafter (q8w). 
     
     
         3 . The method of  claim 2 , wherein the antibody is administered at a dose of between 25 mg and 200 mg. 
     
     
         4 . The method of  claim 2 , wherein the antibody is administered at a dose of 50 mg or 100 mg. 
     
     
         5 . The method of  claim 2 , wherein the antibody is administered at a dose of 100 mg. 
     
     
         6 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the American College of Rheumatology 20% improvement criteria (ACR20) by week 24 of treatment with the antibody. 
     
     
         7 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the American College of Rheumatology 20% improvement criteria (ACR20) by week 16 of treatment with the antibody. 
     
     
         8 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the Psoriasis Area and Severity Index 75, 90 and 100 (PASI75/90/100) by week 24 of treatment with the antibody. 
     
     
         9 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the American College of Rheumatology 50% and 70% improvement criteria (ACR50/70) by week 24 of treatment with the antibody. 
     
     
         10 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the Health Assessment Questionnaire Disability Index (HAQ-DI) by week 24 of treatment with the antibody. 
     
     
         11 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having statistically significant improvement in disease activity as determined by the Leeds enthesitis index (LEI) by week 24 of treatment with the antibody. 
     
     
         12 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having statistically significant improvement in disease activity as determined by the dactylitis assessment score of 0-3 ((0=absent, 1=mild, 2=moderate, 3=severe) by week 24 of treatment with the antibody. 
     
     
         13 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the Short-Form 36 (SF-36) health survey by week 24 of treatment with the antibody. 
     
     
         14 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the mental and physical component summary (MCS and PCS) scores by week 24 of treatment with the antibody. 
     
     
         15 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the minimal disease activity (MDA) criteria by week 24 of treatment with the antibody. 
     
     
         16 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the Psoriatic ArthritiS Disease Activity Score (PASDAS) by week 24 of treatment with the antibody. 
     
     
         17 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the GRAppa Composite scorE (GRACE) Index by week 24 of treatment with the antibody. 
     
     
         18 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the modified Composite Psoriatic Disease Activity Index (mCPDAI) by week 24 of treatment with the antibody. 
     
     
         19 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the Disease Activity Index for PSoriatic Arthritis (DAPSA) by week 24 of treatment with the antibody. 
     
     
         20 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the Routine Assessment of Patient Index Data 3 (RAPID3) by week 24 of treatment with the antibody. 
     
     
         21 . The method of  claim 5 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity by week 24 of treatment, wherein disease activity is determined by one or more criteria selected from the group consisting of the American College of Rheumatology 20% improvement criteria (ACR20), the American College of Rheumatology 50% improvement criteria (ACR50), the Psoriasis Area and Severity Index 75, 90 and 100 (PASI75/90/100), the American College of Rheumatology 50% and 70% improvement criteria (ACR50/70), the Health Assessment Questionnaire Disability Index (HAQ-DI), the Leeds enthesitis index (LEI), the dactylitis assessment score (0=absent, 1=mild, 2=moderate, 3=severe), changes in Short Form Health survey (SF-36), changes in the mental and physical component summary (MCS and PCS), the achievement of minimal disease activity (MDA), the Psoriatic ArthritiS Disease Activity Score (PASDAS), the GRAppa Composite scorE (GRACE) Index, the modified Composite Psoriatic Disease Activity Index (mCPDAI), the Disease Activity Index for PSoriatic Arthritis (DAPSA), and the Routine Assessment of Patient Index Data 3 (RAPID3). 
     
     
         22 . The method of  claim 5 , wherein the ACR20, ACR50, ACR70, PASI70, PASI90, PSAI100, MDA, HAQ-DI, LEI/dactylitis, SF-36 PCS, PASDAS, GRACE, mCPDAI, DAPSA, RAPID3 or MCS score is measured 16, 20, 24 or 28 weeks after initial treatment. 
     
     
         23 . The method of  claim 5 , wherein the antibody is guselkumab administered subcutaneously. 
     
     
         24 . The method of  claim 23 , wherein the antibody is in a composition comprising 100 mg/mL of antibody; 7.9% (w/v) sucrose, 4.0 mM Histidine, 6.9 mM L-Histidine monohydrochloride monohydrate; 0.053% (w/v) Polysorbate 80 of the pharmaceutical composition; wherein the diluent is water at standard state. 
     
     
         25 . The method of  claim 1 , further comprising administering to the patient one or more additional drugs used to treat psoriasis arthritis. 
     
     
         26 . The method of  claim 25 , wherein the additional drug is selected from the group consisting of: immunosuppressive agents, non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate (MTX), anti-B-cell surface marker antibodies, anti-CD20 antibodies, rituximab, TNF-inhibitors, corticosteroids, and co-stimulatory modifiers. 
     
     
         27 . The method of  claim 1 , wherein the antibody is effective to reduce a symptom of psoriatic arthritis in the patient, induce clinical response, induce or maintain clinical remission, inhibit disease progression, or inhibit a disease complication in the patient. 
     
     
         28 . A method of treating psoriatic arthritis in a patient, comprising administering an antibody to IL-23 to the patient in a safe and effective amount, wherein the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 116 and a heavy chain variable region of the amino acid sequence of SEQ ID NO: 106. 
     
     
         29 . The method of  claim 28 , wherein the antibody is administered in an initial subcutaneous dose at week 0, a subcutaneous dose at week 4 and a subcutaneous does every 8 weeks thereafter (q8w). 
     
     
         30 . The method of  claim 28 , wherein the antibody is administered at a dose of between 25 mg and 200 mg. 
     
     
         31 . The method of  claim 28 , wherein the antibody is administered at a dose of 50 mg or 100 mg. 
     
     
         32 . The method of  claim 28 , wherein the antibody is administered at a dose of 100 mg. 
     
     
         33 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the American College of Rheumatology 20% improvement criteria (ACR20) by week 24 of treatment with the antibody. 
     
     
         34 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the American College of Rheumatology 20% improvement criteria (ACR20) by week 16 of treatment with the antibody. 
     
     
         35 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the Psoriasis Area and Severity Index 75, 90 and 100 (PASI75/90/100) by week 24 of treatment with the antibody. 
     
     
         36 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the American College of Rheumatology 50% and 70% improvement criteria (ACR50/70) by week 24 of treatment with the antibody. 
     
     
         37 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the Health Assessment Questionnaire Disability Index (HAQ-DI) by week 24 of treatment with the antibody. 
     
     
         38 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having statistically significant improvement in disease activity as determined by the Leeds enthesitis index (LEI) by week 24 of treatment with the antibody. 
     
     
         39 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having statistically significant improvement in disease activity as determined by the dactylitis assessment score of 0-3 ((0=absent, 1=mild, 2=moderate, 3=severe) by week 24 of treatment with the antibody. 
     
     
         40 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the Short-Form 36 (SF-36) health survey by week 24 of treatment with the antibody. 
     
     
         41 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined by the mental and physical component summary (MCS and PCS) scores by week 24 of treatment with the antibody. 
     
     
         42 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the minimal disease activity (MDA) criteria by week 24 of treatment with the antibody. 
     
     
         43 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the Psoriatic ArthritiS Disease Activity Score (PASDAS) by week 24 of treatment with the antibody. 
     
     
         44 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the GRAppa Composite scorE (GRACE) Index by week 24 of treatment with the antibody. 
     
     
         45 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the modified Composite Psoriatic Disease Activity Index (mCPDAI) by week 24 of treatment with the antibody. 
     
     
         46 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the Disease Activity Index for PSoriatic Arthritis (DAPSA) by week 24 of treatment with the antibody. 
     
     
         47 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity as determined the Routine Assessment of Patient Index Data 3 (RAPID3) by week 24 of treatment with the antibody. 
     
     
         48 . The method of  claim 32 , wherein the patient is a responder to the treatment with the antibody and is identified as having a statistically significant improvement in disease activity by week 24 of treatment, wherein disease activity is determined by one or more criteria selected from the group consisting of the American College of Rheumatology 20% improvement criteria (ACR20), the American College of Rheumatology 50% improvement criteria (ACR50), the Psoriasis Area and Severity Index 75, 90 and 100 (PASI75/90/100), the American College of Rheumatology 50% and 70% improvement criteria (ACR50/70), the Health Assessment Questionnaire Disability Index (HAQ-DI), the Leeds enthesitis index (LEI), the dactylitis assessment score (0=absent, 1=mild, 2=moderate, 3=severe), changes in Short Form Health survey (SF-36), changes in the mental and physical component summary (MCS and PCS), the achievement of minimal disease activity (MDA), the Psoriatic ArthritiS Disease Activity Score (PASDAS), the GRAppa Composite scorE (GRACE) Index, the modified Composite Psoriatic Disease Activity Index (mCPDAI), the Disease Activity Index for PSoriatic Arthritis (DAPSA), and the Routine Assessment of Patient Index Data 3 (RAPID3). 
     
     
         49 . The method of  claim 32 , wherein the ACR20, ACR50, ACR70, PASI70, PASI90, PSAI100, MDA, HAQ-DI, LEI/dactylitis, SF-36 PCS, PASDAS, GRACE, mCPDAI, DAPSA, RAPID3 or MCS score is measured 16, 20, 24 or 28 weeks after initial treatment. 
     
     
         50 . The method of  claim 32 , wherein the antibody is guselkumab administered subcutaneously. 
     
     
         51 . The method of  claim 50 , wherein the antibody is in a composition comprising 100 mg/mL of antibody; 7.9% (w/v) sucrose, 4.0 mM Histidine, 6.9 mM L-Histidine monohydrochloride monohydrate; 0.053% (w/v) Polysorbate 80 of the pharmaceutical composition; wherein the diluent is water at standard state. 
     
     
         52 . The method of  claim 28 , further comprising administering to the patient one or more additional drugs used to treat psoriasis arthritis. 
     
     
         53 . The method of  claim 52 , wherein the additional drug is selected from the group consisting of: immunosuppressive agents, non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate (MTX), anti-B-cell surface marker antibodies, anti-CD20 antibodies, rituximab, TNF-inhibitors, corticosteroids, and co-stimulatory modifiers. 
     
     
         54 . The method of  claim 28 , wherein the antibody is effective to reduce a symptom of psoriatic arthritis in the patient, induce clinical response, induce or maintain clinical remission, inhibit disease progression, or inhibit a disease complication in the patient. 
     
     
         55 . A method of treating psoriatic arthritis in a patient that is a non-responder to a TNF inhibitors, comprising administering an antibody to IL-23 to the patient in a clinically proven safe and clinically proven effective amount, wherein the antibody comprises a light chain variable region and a heavy chain variable region, said light chain variable region comprising: a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:50; a CDRL2 amino acid sequence of SEQ ID NO:56; and a CDRL3 amino acid sequence of SEQ ID NO:73, said heavy chain variable region comprising: a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:5; a CDRH2 amino acid sequence of SEQ ID NO:20; and a CDRH3 amino acid sequence of SEQ ID NO:44. 
     
     
         56 . The method of  claim 55 , wherein the TNF inhibitor is adalilumab or eternacept. 
     
     
         57 . The method of  claim 56 , wherein the patient is determined to be a non-responder to a TNF inhibitors by measuring the PASI70/90/100 and/or ACR20/50/70 score. 
     
     
         58 . A method of treating psoriatic arthritis in a patient that is a non-responder to a TNF inhibitors, comprising administering an antibody to IL-23 to the patient in a clinically proven safe and clinically proven effective amount, wherein the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 116 and a heavy chain variable region of the amino acid sequence of SEQ ID NO: 106. 
     
     
         59 . The method of  claim 58 , wherein the TNF inhibitor is adalilumab or eternacept. 
     
     
         60 . The method of  claim 59 , wherein the patient is determined to be a non-responder to a TNF inhibitors by measuring the PASI70/90/100 and/or ACR20/50/70 score. 
     
     
         61 . A method of treating moderate-to-severe psoriatic arthritis in adult patients who are candidates for systemic therapy or phototherapy, comprising administering an antibody to IL-23 to the patient in a clinically proven safe and clinically proven effective amount, wherein the antibody comprises a complementarity determining region light chain 1 (CDRL1) amino acid sequence of SEQ ID NO:50; a CDRL2 amino acid sequence of SEQ ID NO:56; a CDRL3 amino acid sequence of SEQ ID NO:73; a complementarity determining region heavy chain 1 (CDRH1) amino acid sequence of SEQ ID NO:5; a CDRH2 amino acid sequence of SEQ ID NO:20; and a CDRH3 amino acid sequence of SEQ ID NO:44, the dosage is 100 mg administered by subcutaneous injection at Week 0, Week 4 and every 8 weeks thereafter and the antibody is at a concentration of 100 mg/mL in a single-dose prefilled syringe comprising 7.9% (w/v) sucrose, 4.0 mM Histidine, 6.9 mM L-Histidine monohydrochloride monohydrate; 0.053% (w/v) Polysorbate 80 and the diluent is water at standard state. 
     
     
         62 . A method of treating moderate-to-severe psoriatic arthritis in adult patients who are candidates for systemic therapy or phototherapy, comprising administering an antibody to IL-23 to the patient in a clinically proven safe and clinically proven effective amount, wherein the antibody comprises a light chain variable region of the amino acid sequence of SEQ ID NO: 116 and a heavy chain variable region of the amino acid sequence of SEQ ID NO: 106, the dosage is 100 mg administered by subcutaneous injection at Week 0, Week 4 and every 8 weeks thereafter and the antibody is at a concentration of 100 mg/mL in a single-dose prefilled syringe comprising 7.9% (w/v) sucrose, 4.0 mM Histidine, 6.9 mM L-Histidine monohydrochloride monohydrate; 0.053% (w/v) Polysorbate 80 and the diluent is water at standard state.