Treatment of immune-related and inflammatory diseases

Abstract

Provided herein are methods of using compounds and compositions for modulating leukocytic activity, including activity of B cells and/or T cells monocytes, macrophages, and other lymphoid or myeloid-derived cell types, in immune-related diseases or inflammatory diseases. Pharmaceutical compositions and dosing regimens for use in the methods are also provided herein.

What is claimed is: 
     
         1 . A method for treating, preventing or managing an immune-related disease or an inflammatory disease comprising administering to a patient in need thereof an effective amount of a compound of formula I 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, tautomer or racemic mixture thereof, wherein the disease is lupus pernio or sarcoidosis. 
       
     
     
         2 . The method of  claim 1 , wherein the compound is (S)-3-[4-(4-morphlin-4-ylmethylbenzyloxy)-1-oxo-1,3-dihydro-isoindo-2-yl]piperidine-2,6-dione or a pharmaceutically acceptable salt, solid form, solvate, hydrate, tautomer, stereoisomer or racemate thereof. 
     
     
         3 . The method of  claim 1 , wherein the compound is (S)-3-[4-(4-morphlin-4-ylmethylbenzyloxy)-1-oxo-1,3-dihydro-isoindo-2-yl]piperidine-2,6-dione. 
     
     
         4 . The method of  claim 1 , wherein the compound is (S)-3-[4-(4-morphlin-4-ylmethylbenzyloxy)-1-oxo-1,3-dihydro-isoindo-2-yl]piperidine-2,6-dione hydrochloride. 
     
     
         5 . The method of  claim 1 , wherein the disease is chronic cutaneous sarcoidosis. 
     
     
         6 . The method of  claim 5 , wherein the chronic cutaneous sarcoidosis is with pulmonary involvement. 
     
     
         7 . The method of  claim 5 , wherein the chronic cutaneous sarcoidosis is without pulmonary involvement. 
     
     
         8 . The method of  claim 1  further comprising administering a second active agent, which is an anti-inflammatory or immunomodulatory compound. 
     
     
         9 . The method of  claim 1 , wherein the effective amount is about 0.005 mg/kg to about 10 mg/kg of the patient's body weight. 
     
     
         10 . A method for reducing, inhibiting or preventing a symptom of sarcoidosis comprising administering to a patient having the symptom of sarcoidosis an effective amount of a compound, wherein the symptom is selected from the group consisting of (i) granulomas formulation, (ii) lupus pernio, (iii) skin lesions, (iv) dyspnea, (v) dry cough, (vi) chest pain, and (vii) fatigue, and wherein the compound corresponds to formula I 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, tautomer or racemic mixture thereof. 
       
     
     
         11 . The method of  claim 10 , wherein the compound is (S)-3-[4-(4-morphlin-4-ylmethylbenzyloxy)-1-oxo-1,3-dihydro-isoindo-2-yl]piperidine-2,6-dione or a pharmaceutically acceptable salt, solid form, solvate, hydrate, tautomer, stereoisomer or racemate thereof. 
     
     
         12 . The method of  claim 10 , wherein the compound is (S)-3-[4-(4-morphlin-4-ylmethylbenzyloxy)-1-oxo-1,3-dihydro-isoindo-2-yl]piperidine-2,6-dione. 
     
     
         13 . The method of  claim 10 , wherein the compound is (S)-3-[4-(4-morphlin-4-ylmethylbenzyloxy)-1-oxo-1,3-dihydro-isoindo-2-yl]piperidine-2,6-dione hydrochloride. 
     
     
         14 . The method of  claim 10  further comprising administering a second active agent, which is an anti-inflammatory or immunomodulatory compound. 
     
     
         15 . The method of  claim 10 , wherein the effective amount is about 0.005 mg/kg to about 10 mg/kg of the patient's body weight. 
     
     
         16 . A method for improving the Modified Sarcoidosis Activity and Severity Index (MSASI) score, the Physician's and Subject's Global Assessment of Disease Activity score, the 6WMT score, the FACIT-F score, the Dermoscopy for Lesion Assessment score, the Physician's Overall Skin Response Assessment score, the lesion, one or more biomarkers associated with sarcoidosis, FVC, FEV 1 , the chest radiographic Likert score, the Saint George's Respiratory Questionnaire score, or the dyspnea index (BDI)/transition dyspnea index (TDI) of a patient having sarcoidosis, comprising administering to the patient an effective amount of a compound of formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate, hydrate, stereoisomer, tautomer or racemic mixture thereof. 
       
     
     
         17 . The method of  claim 16 , wherein the compound is (S)-3-[4-(4-morphlin-4-ylmethylbenzyloxy)-1-oxo-1,3-dihydro-isoindo-2-yl]piperidine-2,6-dione or a pharmaceutically acceptable salt, solid form, solvate, hydrate, tautomer, stereoisomer or racemate thereof. 
     
     
         18 . The method of  claim 16 , wherein the compound is (S)-3-[4-(4-morphlin-4-ylmethylbenzyloxy)-1-oxo-1,3-dihydro-isoindo-2-yl]piperidine-2,6-dione. 
     
     
         19 . The method of  claim 16 , wherein the compound is (S)-3-[4-(4-morphlin-4-ylmethylbenzyloxy)-1-oxo-1,3-dihydro-isoindo-2-yl]piperidine-2,6-dione hydrochloride. 
     
     
         20 . The method of  claim 16  further comprising administering a second active agent is an anti-inflammatory or immunomodulatory compound. 
     
     
         21 . The method of  claim 16 , wherein the effective amount is about 0.005 mg/kg to about 10 mg/kg of the patient's body weight.